4.monograph - Part I (A I) PDF

KP 9 21
Monographs, Part I
22 Monographs, Part I
KP 9 23
Acebutolol Hydrochloride
O
C
O
CH3CH2CH2
CH3
OH
NH
OCH2CCH2NHCH(CH3)2
H
graphy. Develop the plate with the upper layer of a mixture of water, n-butanol and glacial acetic acid (5 : 4 : 1)
to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 365 nm).
Any spot other than the principal spot from the test solution is not more intense than the spot from the standard
solution.
HCl
and enantiomer
C18H28N2O4HCl: 372.89
Acebutolol Hydrochloride, when dried, contains not less
than 98.0% and not more than 102.0% of acebutolol hydrochloride (C18H28N2O4 HCl).
Description Acebutolol Hydrochloride is white to pale
yellowish white crystal or crystalline powder.
Acebutolol Hydrochloride is freely soluble in water, in
methanol, in ethanol or in glacial acetic acid and practically insoluble in ether.
A solution of Acebutolol Hydrochloride (1 in 20) shows
no optical rotation.
Identification (1) Determine the absorption spectra of
solutions of Acebutolol Hydrochloride and Acebutolol
Hydrochloride RS, in 0.01mol/L hydrochloric acid TS (1
in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wavelengths.
(2) Determine the infrared spectra of Acebutolol Hydrochloride and Acebutolol Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Acebutolol Hydrochloride (1 in 100)
responds to the Qualitative Tests for chloride.
Melting Point Between 141 C and 145 C.
Purity (1) Heavy metalsProceed with 1.0 g of Acebutolol Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 1.0 mL of
standard lead solution (not more than 10 ppm).
(2) ArsenicPrepare the test solution with 1.0 g of
Acebutolol Hydrochloride according to Method 3 and
perform the test (not more than 2 ppm).
(3) Related substancesDissolve 40 mg of Acebutolol Hydrochloride in 2 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution and add methanol to make exactly 25 mL. Pipet
exactly 1 mL of this solution, add methanol to make exactly 20 mL and use this solution as the standard solution.
Perform the test with the test solution and the standard
solution as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the standard
solution on a plate of silica gel for thin-layer chromato-
Loss on Drying Not more than 1.0% (0.5 g, 105 C, 3

hours).
Residue on Ignition Not more than 0.2% (1 g).
Assay Weigh accurately about 0.25 g of Acebutolol
Hydrochloride, previously dried, dissolve in 20 mL of
glacial acetic acid, add 80 mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid VS (potentiometric
titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid VS
= 37.289 mg of C18H28N2O4HCl
Packaging and Storage Preserve in well-closed containers.
Aceclofenac
O
Cl
COOH
H
N
Cl
C16H13Cl2NO4: 354.19
Aceclofenac, when dried, contains not less than 99.0%
and not more than 101.0% of aceclofenac
(C16H13Cl2NO4).
Description Aceclofenac is a white crystalline powder.
Aceclofenac is freely soluble in acetone or in dimethylformamide, soluble in ethanol or in methanol, and practically insoluble in water.
Identification (1) Dissolve 10 mg of Aceclofenac in 10
mL of ethanol, and to 1 mL of this solution, add 0.2 mL
of a mixture of equal volume of a solution of potassium
ferricyamide (6 in 1000) and a solution of ferric chloride
(9 in 1000). Allow to stand in the dark for 5 minutes, add
3 mL of a solution of hydrochloric acid (10 in 1000), and
allow to stand in the dark for 15 minutes again: A blue
color develops and a precipitate is formed.
(2) Dissolve 50 mg of Aceclofenac in 100 mL of methanol, and to 2 mL of this solution, add methanol to
make 50 mL, and determine the absorption spectrum of
this solution between 220 nm and 370 nm as directed
under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum at 275 nm. The specific absorbance at
the maximum is 320 to 350.
(3) Determine the infrared spectra of Aceclofenac
and Aceclofenac RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry:
both spectra exhibit similar intensities of absorption at
the same wavenumbers.
Purity (1) Heavy metalsProceed with 2.0 g of Aceclofenac according to Method 2, and perform the test.
Prepare the control solution with 2.0 mL of standard lead
solution (not more than 10 ppm).
(2) Related substancesDissolve 0.1 g of Aceclofenac, accurately weighed, in 50 mL of the mobile phase,
and use this solution as the test solution. Dissolve diclofenac sodium RS, equivalent to 5 mg of diclofenac, in 50
mL of the mobile phase, and use this solution as the
standard solution (1). Pipet 2 mL of the standard solution
(1), add the mobile phase to make 50 mL, and use this
solution as the standard solution (2). Pipet 5 mL of the
standard solution (1), add 0.25 mL of the test solution,
add the mobile phase to make 50 mL, and use this solution as the standard solution (3). Perform the test with 10
L each of the test solution and the standard solution (2)
as directed under the Liquid Chromatography according
to the following conditions. Determine each peak area of
these solutions: the area of each peak other than the peak
of Aceclofenac from the test solution is not larger than
the peak area of Aceclofenac from the standard solution
(2) (not more than 0.2%), and the total area of each peak
other than the peak of Aceclofenac from the test solution
is not more than 2.5 times of the peak area of Aceclofenac from the standard solution (2) (not more than 0.5%).
Omit the peak from the test solution, which peak area is
less than 0.2 times of the peak area of the main peak
from the standard solution (2).
Operating conditions
Detector: An ultraviolet absorption photometer (wavelength: 275 nm).
Column: A stainless steel column, about 4 mm in inside diameter and about 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
m in particle diameter).
Mobile phase: Adjust the pH of a mixture of acetonitile, tetrahydrofuran, and glacial acetic acid (1.2 in 1000)
(225 : 225 : 550) to 3.5 with sodium hydroxide TS.
Flow rate: 1 mL/minute
System suitability:
System performance: When the procedure is run
with 10 L of the standard solution (3) under the above
operating conditions, Aceclofenac and diclofenac are
eluted in this order with the resolution between their
peaks being not less than 8.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Aceclofenac and diclofenac
obtained from the standard solution (3) composes 50% of

the full scale.
Time span of measurement: About 10 times as
long as the retention time of Aceclofenac.
Loss on Drying Not more than 0.5% (1.0 g, between
100 C and 105 C)
Residue on Ignition Not more than 0.1% (1.0 g).
Assay Weigh accurately about 0.3 g of Aceclofenac,
previously dried, dissolve in exact 40 mL of methanol,
and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any
necessary correction.
Each mL of 0.1 mol/L sodium hydroxide VS
= 35.419 mg of C16H13Cl2NO4
Packaging and Storage
well-closed containers
Preserve in light-resistant,
Acetaminophen
O
CH3
Paracetamol
NH
OH
C8H9NO2: 151.16
Acetaminophen, when dried, contains not less than

98.0% and not more than 101.0% of acetaminophen
(C8H9NO2).
Description Acetaminophen is a white crystal or crystalline powder.
Acetaminophen is freely soluble in methanol or in ethanol, sparingly soluble in water, and very slightly soluble
in ether.
Acetaminophen dissolves in sodium hydroxide TS.
Identification Determine the infrared spectra of Acetaminophen and Acetaminophen RS, previously dried, as
directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar
intensities of absorption at the same wavenumbers.
Melting Point
Between 169 C and 172 C.
Purity (1) ChlorideDissolve 4.0 g of Acetaminophen in 100 mL of water by heating, cool with shaking in
ice-water, allow to stand until ordinary temperature is attained, add water to make 100 mL and filter. To 25 mL of
the filtrate, add 6 mL of dilute nitric acid and water to
make 50 mL and perform the test using this solution as
the test solution. Prepare the control solution with 0.40
KP 9 25
mL of 0.01 mol/L hydrochloric acid VS (not more than
0.014%).
(2) SulfateTo 25 mL of the filtrate, obtained in (1),
add 1 mL of dilute hydrochloric acid and water to make
50 mL and perform the test using this solution as the test
solution. Prepare the control solution with 0.40 mL of
0.005 mol/L sulfuric acid VS (not more than 0.019%).
(3) Heavy metalsProceed with 2.0 g of Acetaminophen according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Acetaminophen according to Method 3 and perform the
test using Apparatus B (not more than 2 ppm).
(5) Related substancesDissolve 50 mg of Acetaminophen in 1 mL of methanol, add the mobile phase to
make 50 mL and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add the mobile
phase to make exactly 200 mL and use this solution as
the standard solution. Perform the test with 10 L each
of the test solution and the standard solution as directed
under the Liquid Chromatography according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total
area of all peaks other than the peak area of Acetaminophen from the test solution is not larger than the peak
area of Acetaminophen from the standard solution.
Column temperature: A constant temperature of
about 40 C.
Mobile phase: A mixture of 0.05 mol/L monobasic
potassium phosphate TS, pH 4.7 and methanol (4:1).
Flow rate: Adjust the flow rate so that the retention
time of Acetaminophen is about 5 minutes.
System Suitability
System performance: Dissolve 10 mg each of Acetaminophen and p-aminophenol in 1 mL of methanol,
add the mobile phase to make 50 mL. To 1 mL of this solution add the mobile phase to make 10 mL. When the
procedure is run with 10 L of this solution under the
above operating conditions. p-Aminophenol and Acetaminophen are eluted in this order with the resolution between their peaks being not less than 7.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Acetaminophen obtained
from 10 L of the standard solution is about 15% of the
full scale.
Time span of measurement: About 6 times as long
as the retention time of Acetaminophen after the solvent
peak.
hours).
Assay Weigh accurately about 20 mg each of Acetaminophen and Acetaminophen RS, previously dried, dissolve in 2 mL of methanol and add water to make exactly
100 mL. Pipet exactly 3 mL each of these solutions, add
water to make exactly 100 mL and use these solutions as
the test solution and the standard solution, respectively.
Determine the absorbance, AT and AS , of the test solution and the standard solution, respectively, at the wavelength of maximum absorption at about 244 nm as directed under the Ultraviolet-visible Spectrophotometry,
using water as the blank.
Amount (mg) of acetaminophen (C8H9NO2)
= amount (mg) of Acetaminophen RS
tight containers
AT
AS
Acetaminophen Tablets
Paracetamol Tablets
Acetaminophen Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of acetaminophen (C8H9NO2: 151.17).
Method of Preparation Prepare as directed under Tablets, with Acetaminophen.
Identification (1) The retention time of main peak of
the test solution and the standard solution for Assay is
the same.
(2) Weigh a portion of powdered Acetaminophen
Tablets, equivalent to 50 mg of Acetaminophen according to labeled amount, add 50 mL of methanol and mix,
filter and use this filtrate as the test solution. Separately,
weigh 5 mg of Acetaminophen RS, add methanol to
make 5 mL and use this solution as the standard solution.
solution as directed under Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for
thin-layer chromatography. Develop the plate with the
upper layer of a mixture of dichloromethane and methanol (4 : 1) to a distance of about 10 cm and air-dry the
plate. Examine under ultraviolet light (main wavelength:
254 nm). The Rf values of the spots from the test solution and the standard solution are the same.
Dissolution Test Perform the test with 1 tablet of Acetaminophen Tablets at 50 revolutions per minute accord-
ing to Method 2 under the Dissolution Test, using 900
mL of diluted phosphate buffer solution, pH 5.8, as the
dissolution solution. Take the dissolution solution 30 minutes after starting the test, make any necessary dilution
of the filtrate by adding the dissolution solution and use
this solution as the test solution. Separately, weigh accurately about sufficient quantity of Acetaminophen RS,
previously dried in a dessicator (silica gel for 18 hours)
and dissolve in the test solution, to make the same concentration as the test solution and use this solution as the
standard solution. Determine the absorbances of the test
solution and the standard solution at 243 nm as directed
under Ultraviolet-visible Spectrophotometry.
The dissolution rate of Acetaminophen Tablets in 30 minutes should be not less than 80%.
Phosphate buffer solution, pH 5.8To 50 mL of 0.2
mol/L dibasic potassium phosphate TS, add 3.6 mL of
0.2 mol/L of sodium hydroxide TS and add water to
make 200 mL.
Uniformity of Dosage Units It meets the requirement.
Assay Weigh accurately and powder not less than 20
Acetaminophen Tablets. Weigh accurately equivalent to
about 0.1 g of Acetaminophen, add 100 mL of mobile
phase, shake for 10 minutes, then shake strongly for 5
minutes, add mobile phase to make 200 mL, pipet exactly 5 mL of this solution, add mobile phase to make 250
mL and filter through a membrane filter with pore size of
not more than 0.5 m. Discard the first 10 mL of the filtrate, and use the subsequent filtrate as the test solution.
Separately, weigh accurately about 20 mg of Acetaminophen RS, previously dried in 105 C for 2 hours, dissolves in mobile phase to make exactly 100 mL, pipet
exactly 5 mL of this solution, add mobile phase to make
exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and determine, AT and AS , of the peak area of
Acetaminophen.

with 10 L of the standard solution under the above operating condition, the symmetry factor of the peak of
acetaminphen is not more than 2.0.
System repeatability: When the test is repeated 6
times with 10 L of the standard solution under the
above operating conditions, the relative standard deviation of the peak areas is not more than 2.0%.
Packaging and Storage Preserve in tight containers.
Acetazolamide
O
CH3
O
H
N
NH2
O
N
C4H6N4O3S2: 222.25
Acetazolamide contains not less than 98.0% and not
more than 102.0% of acetazolamide (C4H6N4O3S2), calculated on the dried basis.
Description Acetazolamide is a white to pale yellowish white, crystalline powder, is odorless and has a
slight bitter taste.
Acetazolamide is slightly soluble in ethanol, very
slightly soluble in water, and practically insoluble in ether.
Melting pointAbout 255 C (with decomposition)
= amount (mg) of Acetaminophen RS AT 5
Identification (1) To 0.1 g of Acetazolamide, add 5 mL

of sodium hydroxide TS, then add 5 mL of a solution of
0.1 g of hydroxylamine hydrochloride and 50 mg of cupric sulfate in 10 mL of water: a pale yellow color develops. Then heat this solution for 5 minutes: a deep yellow
color is produced gradually.
(2) To 20 mg of Acetazolamide, add 2 mL of dilute
hydrochloric acid, boil for 10 minutes, cool and add 8
mL of water: this solution responds to the Qualitative
Tests for primary aromatic amines.
(3) To 0.2 g of Acetazolamide, add 0.5 g of granulated zinc and 5 mL of diluted hydrochloric acid (1 in 2):
the gas evolved darkens moistened lead acetate paper.
Detector: An ultraviolet absorption spectrophotometer (wavelength: 243 nm).
m to 10 m in particle diameter).
Mobile phase: A mixture of water and methanol (3 :
1).
Flow rate: 1.5 mL/minute.
System suitability
Purity (1) Clarity and color of solutionDissolve 1.0

g of Acetazolamide in 10 mL of sodium hydroxide TS:
the solution is clear and colorless to pale yellow.
(2) ChlorideTo 1.5 g of Acetazolamide, add 75 mL
of water and warm at 70 C for 20 minutes with occasional shaking. After cooling, filter and to 25 mL of the
filtrate, add 6 mL of dilute nitric acid and water to make
50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.20 mL of 0.01
mol/L hydrochloric acid VS (not more than 0.014%).
(3) SulfateTo 25 mL of the filtrate obtained in (2),
Amount (mg) of acetaminophen (C8H9NO2)

AS
KP 9 27
50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of
(4) Heavy metalsProceed with 1.0 g of Acetazolamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(5) Silver-reducing substancesWet 5 g of Acetazolamide with 5 mL of aldehyde-free ethanol and add 125
mL of water, 10 mL of nitric acid and exactly 5 mL of
0.1 mol/L silver nitrate VS. Stir for 30 minutes while
protected from light, filter through a glass filter (G3) and
wash the residue on the glass filter with two 10 mL volumes of water. Combine the filtrate with the washings,
to the solution, add 5 mL of ferric ammonium sulfate TS
and titrate with 0.1 mol/L ammonium thiocyanate VS:
not less than 4.8 mL of 0.1 mol/L ammonium thiocyanate
VS is consumed.
hours).
Assay Weigh accurately about 0.15 g of Acetazolamide
and dissolve in 400 mL of water in a water-bath. After
cooling, add water to make exactly 1000 mL. Pipet exactly 5 mL of the solution, add 10 mL of 1 mol/L hydrochloric acid TS and then add water to make exactly
100 mL. Determine the absorbance A of this solution at
the wavelength of maximum absorption at about 265 nm
as directed under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of acetazolamide (C4H6N4O3S2)
A
= 474 200000

well-closed containers.
Acetohexamide
CH3
O
NH
NH
C15H20N2O4S: 324.40
Acetohexamide, when dried, contains not less than
98.0% and not more than 101.0% of acetohexamide
(C15H20N2O4S).
Description Acetohexamide is a white to yellowish
white powder.
Acetohexamide is freely soluble in dimethylformamide,
sparingly soluble in acetone, slightly soluble in methanol

or in ethanol, and practically insoluble in water.
Identification (1) Dissolve 0.10 g each of Acetohexamide and Acetohexamide RS in 100 mL of methanol.
To 5 mL each of these solutions, add 20 mL of 0.5 mol/L
hydrochloric acid TS and 75 mL of methanol and pipet
exactly 10 mL each of these solutions and dilute with
methanol to exactly 50 mL. Determine the absorption
spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry, using methanol as the
blank, respectively: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Acetohexamide and Acetohexamide RS, previously dried, as directed in the potassium bromide disk method under the
Purity (1) ChlorideDissolve 1.5 g of Acetohexamide in 40 mL of dimethylformamide, add 6 mL of dilute nitric acid and dimethylformamide to make 50 mL.
Perform the test using this solution as the test solution.
Prepare the control solution as follows: to 0.45 mL of
0.01 mol/L hydrochloric acid VS, add 6 mL of dilute nitric acid and dimethylformamide to make 50 mL (not
more than 0.011%).
(2) SulfateDissolve 2.0 g of Acetohexamide in 40
mL of dimethylformamide and add 1 mL of dilute hydrochloric acid and dimethylformamide to make 50 mL.
0.005 mol/L sulfuric acid VS, add 1 mL of dilute hydrochloric acid and dimethylformamide to make 50 mL
(not more than 0.010%).
(3) Heavy metalsProceed with 1.0 g of Acetohexamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(4) Related substances (i) Cyclohexylamine Dissolve exactly 1.0 g of Acetohexamide in exactly 30 mL
of 0.5 mol/L sodium hydroxide TS, add exactly 5 mL of
hexane, shake vigorously for 60 minutes, allow to stand
for 5 minutes, and use the upper layer as the test solution.
Separately, dissolve about 50 mg of Cyclohexylamine
RS, accurately weighed, in 0.5 mol/L sodium hydroxide
TS to make exactly 50 mL. Pipet exactly 2 mL of this solution, and add 0.5 mol/L sodium hydroxide TS to make
exactly 300 mL. Pipet 30 mL of this solution, add exactly
5 mL of hexane, shake vigorously for 60 minutes, allow
to stand for 5 minutes, and use the upper layer as the
standard solution. Perform the test with exactly 2 L
each of the test solution and standard solution as directed
under Gas Chromatography according to the following
conditions, and determine the peak area of cyclohexylamine by the automatic integration method: the peak area
of cyclohexylamine is not more than that with the standard solution.
Detector: A hydrogen flame-ionization detector.
Column: A fused-silica column 0.53 mm in inside diameter and 30 cm in length, coated the inner surface with
methylsilicone polymer for Gas Chromatography 1.5 m
in thickness.
about 90 C.
Injection port temperature: A constant temperature of
about 150 C.
Detector temperature: A constant temperature of
about 210 C.
Carrier gas: Helium
time of cyclohexylamine is about 4 minutes.
System suitability
with 2 L of the standard solution under the above operating conditions, the number of theoretical plates of the
peak of cyclohexylamine is not less than 8000.
times with 2 L of the standard solution under the above
operating conditions, the relative standard deviation of
the peak area of cyclohexylamine is not more than 5.0%.
(ii) DicyclohexylureaDissolve 1.0 g of Acetohexamide, accurately weighed, in exactly 10 mL of 0.5
mol/L sodium hydroxide TS, add exactly 20 mL of methanol, shake, then add exactly 5 mL of diluted hydrochloric acid (1 in 10), shake vigorously for 15 minutes, and
centrifuge. Filter 10 mL or more of the supernatant liquid
through a membrane filter with pore size of not larger
than 0.5 m. Discard the first 5 mL of the filtrate, and
use the subsequent filtrate as the test solution. Separately,
weigh accurately about 50 mg of dicyclohexylurea RS,
dissolve with methanol to make exactly 100 mL. Pipet
exactly 2 mL of this solution, add methanol to make exactly 100 mL, pipet exactly 20 mL of this solution, add
exactly 10 mL of 0.5 mol/L sodium hydroxide TS, shake,
then add exactly 5 mL of diluted hydrochloric acid (1 in
10), shake, and use this solution as the standard solution.
Perform the test with exactly 50 L each of the test solution and the standard solution as directed under Liquid
Chromatography according to the following conditions,
and determine the peak area of dicyclohexylurea by the
automatic integration method: the peak area of dicyclohexylurea obtained with the test solution is not more than
that with the standard solution.
Column: A stainless steel column 4.6 mm in inside
diameter and 25 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (5 m in particle diameter).
about 25 C.
Mobile phase: Dissolve 0.5 g of sodium hydroxide in
1000 mL of 0.05 mol/L sodium dihydrogen phosphate

TS, and adjust to pH 6.5 with 0.5 mol/L sodium hydroxide TS. To 500 mL of this solution add 500 mL of acetonitrile.
time of dicyclohexylurea is about 10 minutes.
System suitability
peak of dicyclohexylurea is not less than 10000.
above operating conditions, the relative standard deviation of the peak area of dicylohexylurea is not more than
2.0%.
(iii) Other related substancesDissolve 0.1 g of Acetohexamide in 10 mL of acetone and use this solution as
the test solution. Pipet exactly 1 mL of this solution, add
acetone to make exactly 20 mL. Pipet exactly two 1-mL
portions of this solution, add acetone to make exactly 10
mL and 25 mL, respectively, and use these solutions as
the standard solutions (1) and (2). Perform the test with
these solutions as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the
standard solutions (1) and (2) on a plate of silica gel with
fluorescent indicator for thin-layer chromatography and
dry the plate. Then, develop the plate with a mixture of
ethyl acetate, methanol, cyclohexane and strong ammonia water (6 : 2 : 1 : 1) to a distance of about 10 cm and
dry the plate with air. Examine under ultraviolet light
(main wavelength: 254 nm): any spot other than the principal spot from the test solution is not more intense than
that from the standard solution (1) and the number of
spots being more intense than that from the standard solution (2) is not more than 4.
Loss on Drying Not more than 1.0% (1 g, 105 C, 4
hours).
Assay Weigh accurately about 0.3 g of Acetohexamide,
previously dried, dissolve in 30 mL of dimethylformamide, add 10 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint
Detection Method in Titrimetry). Perform a blank determination using a solution prepared by adding 19 mL of
water to 30 mL of dimethylformamide and make any
= 32.440 mg of C15H20N2O4S
KP 9 29
Acetylcholine Chloride for

Injection
CH3
H3C
CH2CH2OCOCH3
Cl
line Chloride for Injection according to Method 1 and

perform the test. Prepare the control solution with 2.0
mL of standard lead solution (not more than 10 ppm).
Sterility Test It meets the requirement.
Foreign Insoluble Matter Test It meets the requirement.
CH3
C7H16ClNO2: 181.66
Acetylcholine Chloride for Injection is a preparation for
injection which is dissolved before use. Acetylcholine
Chloride for Injection contains not less than 98.0% and
not more than 102.0% of acetylcholine chloride
(C7H16ClNO2) and not less than 19.3% and not more than
19.8% of chlorine (Cl: 35.45), calculated on the dried basis. Acetylcholine Chloride for Injection contains not less
than 93.0% and not more than 107.0% of the labeled
amount of acetylcholine chloride (C7H16ClNO2).
Method of Preparation Prepare as directed under Injections.
Description Acetylcholine Chloride for Injection is a
white crystal or crystalline powder.
Acetylcholine Chloride for Injection is very soluble in
water, freely soluble in ethanol.
Acetylcholine Chloride for Injection is extremely hygroscopic.
Identification (1) Determine the infrared spectra of
Acetylcholine Chloride for Injection and Acetylcholine
Chloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) A solution of Acetylcholine Chloride for Injection
in water (1 in 10) responds to the Qualitative Tests (2)
for chloride.
Melting Point Between 149 C and 152 C. Seal Acetylcholine Chloride for Injection in a capillary tube for
melting point determination immediately after drying
both the sample and the tube at 105 C for 3 hours and
determine the melting point.
g of Acetylcholine Chloride for Injection in 10 mL of
water: the solution is clear and colorless.
(2) AcidityDissolve 1.0 g of Acetylcholine Chloride for Injection in 10 mL of freshly boiled and cooled
water, and add 1 drop of bromthymol blue TS, and use
this solution as the test solution. To the test solution add
0.30 mL of 0.01 mol/L sodium hydroxide VS: the solution is blue in color.
(3) Heavy metalsProceed with 2.0 g of Acetylcho-
Insoluble Particulate Matter Test for Injections

meets the requirement.
It

hours).
Assay (1) Acetylcholine chlorideWeigh accurately
the contents of not less than 10 Acetylcholine Chloride
for Injections. Weigh accurately about 0.5 g of the contents, dissolve in 15 mL of water, then add exactly 40 mL
of 0.1 mol/L sodium hydroxide VS, stopper loosely and
heat on a water-bath for 30 minutes. Cool quickly and titrate the excess sodium hydroxide with 0.05 mol/L sulfuric acid VS (indicator: 3 drops of phenolphthalein TS).
Perform a blank determination and make any necessary
correction.
= 18.166 mg of C7H16ClNO2
(2) ChlorineTitrate the solution, which has been titrated in (1), with 0.1 mol/L silver nitrate VS (indicator:
3 drops of fluorescein sodium TS).
Each mL of 0.1 mol/L silver nitrate VS
= 3.5453 mg of Cl
Packaging and Storage Preserve in hermetic containers.
Acetylcysteine
O
OH
HS
H3C
NH
C5H9NO3S: 163.20
Acetylcysteine, when dried, contains not less than 98.0%
and not more than 102.0% of acetylcysteine (C5H9NO3S).
Description Acetylcysteine is a white, crystalline
powder.
Acetylcysteine is freely soluble in water or ethanol, and
practically insoluble in dichloromethane.
Acetylcysteine and Acetylcysteine RS, respectively, as
Specific Optical Rotation [ ]20
D : Between +21 and
+27 Weigh accurately about 1.25 g of Acetylcysteine,
dissolve in 1 mL of disodium ethylenediaminetetraacetate solution (1 in 100) and 7.5 mL of sodium hydroxide
solution (1 in 25), and add phosphate buffer solution, pH
7.0, to make 25 mL, and determine the optical rotation of
this solution.
pH 7.0 phosphate buffer solutionAdd 50 mL of 1
mol/L monobasic potassium phosphate TS and 29.5 mL
of 1 mol/L sodium hydroxide solution to a volumetric
flask, adjust to a pH of 7.0 by adding water, and add water again to make 100 mL.
pH Dissolve 1.0 g of Acetylcysteine in 100 mL of
freshly boiled and cooled water: the pH of this solution is
between 2.0 and 2.8.
Purity Heavy metals Proceed with 2.0 g of Acetylcysteine according to Method 2, and perform the test.
Prepare the control solution with 2.0 mL of lead standard
Amount (mg) of Acetylcysteine (C5H9NO3S)

= amount (mg) of Acetylcysteine RS
QT
QS
Internal standard solutionDissolve of 1 g of dlphenylalanine in freshly prepared sodium metabisulfite

solution (1 in 2000) to make 200 mL.
Column: A stainless steel column, about 3.9 mm in
inside diameter and about 30 cm in length, having octadecylsilanized silica gel for liquid chromatography (3
Column temperature: A room temperature.
Mobile phase: A solution of potassium dihydrogen
phosphate, pH 3.0 (6.8 in 1000).
System suitability
with 5 L of the standard solution under the above operating conditions, acetylcystein and dl-phenylalanine are
the ratios of the peak area is not more than 2.0%.
Loss on Drying Not more than 0.1% (1 g, in vacuum

at the pressure not exceeding 0.67 kPa, 70 C, 4 hours).
Acrinol Hydrate
NH2
Residue on Ignition Not more than 0.5% (2 g, 600 C).
OCH2CH3 OH
Assay Weigh accurately about 1.0 g of Acetylcysteine,

previously dried, dissolve in freshly prepared sodium
metabisulfite solution (1 in 2000) to make exactly 100
mL. Pipet exactly 10 mL of this solution, add exactly 10
mL of the internal standard solution, then add sodium
metabisulfite solution (1 in 2000) to make exactly 200
mL, and use this solution as the test solution. Separately,
dissolve about 1.0 g of Acetylcysteine RS, accurately
weighed, in sodium metabisulfite solution (1 in 2000) to
make exactly 100 mL. Pipet exactly 10 mL of this solution, add exactly 10 mL of the internal standard solution,
then add sodium metabisulfite solution (1 in 2000) to
make exactly 200 mL, and use this solution as the standard solution. Perform the test with 5 L each of the test
solution and the standard solution as directed under the
Liquid Chromatography according to the following conditions, and calculate the ratios, QT and QS , of the
peak area of Acetylcysteine to that of the internal standard, respectively.
CH3CHCO2H
H2N
Ethacridine Lactat
H2O
C15H15N3OC3H6O3H2O: 361.39
Acrinol Hydrate, contains not less than 98.5% and not

more than 101.0% of acrinol (C15H15N3OC3H6O3 :
343.38), calculated on the anhydrous basis.
Description Acrinol Hydrate is a yellow, crystalline
powder.
Acrinol Hydrate is freely soluble in hot water, sparingly
soluble in water, and slightly soluble in ethanol.
pHThe pH of an aqueous solution of Acrinol Hydrate (1 in 100) is between 5.5 and 7.0.
solutions of Acrinol Hydrate and Acrinol Hydrate RS, in
KP 9 31
water (3 in 250000) as directed under Ultraviolet-visible
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Acrinol Hydrate
and the Acrinol Hydrate RS as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) To 5 mL of a solution of Acrinol Hydrate in water
(1 in 100), add 5 mL of dilute sulfuric acid, shake well,
allow to stand for about 10 minutes at room temperature
and filter: the filtrate responds to the Qualitative Tests for
lactate.
Purity (1) ChlorideDissolve 1.0 g of Acrinol Hydrate in 80 mL of water by warming in a water-bath, cool
and add 10 mL of sodium hydroxide TS and water to
make 100 mL. Shake well, allow to stand for 30 minutes,
filter, to 40 mL of the filtrate, add 7 mL of dilute nitric
acid and water to make 50 mL and perform the test using
this solution as the test solution. Prepare 50 mL of the
control solution with 4 mL of sodium hydroxide TS, 7
mL of dilute nitric acid, 0.30 mL of 0.01 mol/L hydrochloric acid VS and water (not more than 0.026%).
(2) Heavy metalsProceed with 1.0 g of Acrinol
Hydrate according to Method 2 and perform the test.
(3) Volatile fatty acidsDissolve 0.5 g of Acrinol
Hydrate in a mixture of 20 mL of water and 5 mL of dilute sulfuric acid, shake well, filter and heat the filtrate:
no odor of volatile fatty acids is perceptible.
(4) Related substancesDissolve 10 mg of Acrinol
Hydrate in 25 mL of the mobile phase, and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add the mobile phase to make exactly 100 mL,
and use this solution as the standard solution (1). Pipet
exactly 1 mL of standard solution (1), add the mobile
phase to make exactly 10 mL, and use this solution as the
standard solution (2). Perform the test with exactly 10 L
each of the test solution and the standard solutions (1)
and (2) as directed under Liquid Chromatography according to the following conditions, and determine each
peak area by the automatic integration method: the area
of any peak other than acrinol obtained with the test solution is not larger than 3 times the peak area of acrinol
obtained with the standard solution (2), and the total area
of all peaks other than acrinol obtained with the test solution is not larger than the peak area of acrinol with the
standard solution (1).
about 25 C.
Mobile phase: Dissolve 7.8 g of sodium dihydrogen
phosphate in 900 mL of water, adjust to pH 2.8 with
phosphoric acid, and add water to make 1000 mL. To
700 mL of this solution add 300 mL of acetonitrile for
Liquid Chromatography, and add 1.0 g of sodium 1octanesulfonate to dissolve.
time of acrinol is about 15 minutes.
System suitability
Test for required detectability: Confirm that the
peak area of acrinol obtained with 10 L of the standard
solution (2) is equivalent to 7 to 13% of that with 10 L
of the standard solution (1).
operating conditions, the number of theoretical plates
and the symmetry factor of the peak of acrinol are not
less than 5000 and not more than 2.0, respectively.
times with 10 L of the standard solution (1) under the
above operating conditions, the relative standard deviation of the peak area of acrinol is not more than 1.5%.
as the retention time of acrinol beginning after the solvent peak.
Water Between 4.5and 5.5% (0.2 g, volumetric titration, direct titration)
Assay Weigh accurately about 0.27 g of Acrinol Hydrate, dissolve in 5 mL of formic acid, add 60 mL of a
mixture of acetic anhydride and glacial acetic acid (1 : 1),
and titrate immediately with 0.1 mol/L perchloric acid
VS (potentiometric titration, Endpoint Detection Method
in Titrimetry). Perform a blank determination in the same
manner, and make any necessary correction.
= 34.34 mg of acrinol (C15H15N3OC3H6O3)
tight containers.
Acyclovir
O
N
HN
OH
H2N
N
O
C8H11N5O3: 225.21
Acyclovir contains not less than 98.0% and not more
than 101.0% of acyclovir (C8H11N5O3), calculated on the
anhydrous basis.
Description Acyclovir is a white crystalline powder.
Acyclovir is freely soluble in dimethylsulfoxide, slightly
soluble in water, and very slightly soluble in ethanol.
Acyclovir dissolves in dilute hydrochloric acid.
Acyclovir and Acyclovir RS, respectively, as directed in
the potassium bromide disk method under the Infrared
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) The retention time of main peak of the test solution for Assay and the standard solution is the same.
Water Not more than 6.0% (0.5 g, volumetric trtration,
direct titration)
Purity (1) Related substancesDissolve a certain
amount of Acyclovir, accurately weighed, in dimethylsulfoxide to contain about 10 mg per mL of Acyclovir,
and use this solution as the test solution. Pipet exactly 1
mL of this solution, add dimethylsulfoxide to make exactly 100 mL, and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of chloroform, methanol, and strong ammonia water (80 : 20 : 2) to a distance of about 15 cm,
and air-dry the plate. Examine under ultraviolet light
(main wavelength: 254 and 366 nm): the spots other than
principal spot from the test solution are not more intense
than the spot from the standard solution (not more than
1%)
(2) GuanineDissolve about 0.1 g of Acyclovir, accurately weighed, in water to make exactly 200 mL. Pipet exactly 10 mL of this solution, add 0.01 mol/L sodium hydroxide TS to make exactly 50 mL, and use this
solution as the test solution. Separately, dissolve about
8.8 mg of Guanine RS, accurately weighed, in 50 mL of
0.1 mol/L sodium hydroxide TS, add water to make exactly 500 mL. Pipet exactly 2 mL of this solution, add
0.01 mol/L sodium hydroxide TS to make exactly 50 mL,
and use this solution as the standard solution. Perform
the test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate
the peak areas of guanine, AT and AS , for the test solution and the standard solution, respectively (not more
than 0.7%).
Amount (g) of guanine (C5H5N5O) = 1000 C AT
AS
C: Concentration of the standard solution (g/mL),

Assay Dissolve about 0.1 g of Acyclovir, accurately
weighed, in 20 mL of 0.1 mol/L sodium hydroxide TS,
and add water to make exactly 200 mL. Pipet exactly 10
mL of this solution, add 0.01 mol/L sodium hydroxide
TS to make exactly 50 mL, and use this solution as the
test solution. Separately, dissolve about 25 mg of Acyclovir RS, accurately weighed, in 5 mL of 0.1 mol/L sodium hydroxide TS, add water to make exactly 50 mL.
Pipet exactly 10 mL of this solution, add 0.01 mol/L sodium hydroxide TS to make exactly 50 mL, and use this
solution as the standard solution. Perform the test with
20 L each of the test solution and the standard solution
to the following conditions, and calculate the peak areas
of acyclovir, AT and AS , for the test solution and the
standard solution, respectively.
Amount (g) of acyclovir (C8H11N5O3)
= 1000 C AT
AS
C: Concentration of Acyclovir RS in the standard solution (g/mL)

inside diameter and about 25 cm in length, packed with
octadecylsilanized silica gel for liquid chromatography
(3 m to 10 m in particle diameter).
Mobile phase: Glacial acetic acid solution (1 in 1000).
Flow rate: 3 mL/minute.
System suitability
with 40 L of the mixture of equal volumes of the standard solution in the Purity (2) under Acyclovir and the
standard solution in Assay Acyclovire RS under the
above operating conditions, Acyclovir and guanine are
above operating conditions, the relative standard deviation of the peak areas is not more than 2.0%.
KP 9 33

D : Between -68 to -72
(after drying, 0.4 g, sodium hydroxide solution (1 in 10),
20 mL, 100 mm).
of water. Stir for 30 seconds, pass through a coarse filter,

and use the filtrate as the test solution. Prepare a sulfate
standard solution by adding 0.15 mL of 0.01 mol/L sulfuric acid to 15 mL of water. To the test solution and the
standard solution add 2 mL of barium chloride TS and 1
mL of 3 mol/L hydrochloric acid, dilute each solution
with water to 30 mL, and mix. Allow the solutions to
stand for 5 minutes: the test solution is not more turbid
than the standard solution (not more than 0.02%).
(4) Ammonia Suspend 0.5 g of Adenosine in 10
mL of water. Stir for 30 seconds, pass through a coarse
filter. Dilute the filtrate with water to 15 mL, mix, and
use the filtrate as the test solution. Dilute 1 mL of ammonium chloride solution (314 mg in 1000 mL) with 100
mL of water. Mix 2 mL of this ammonia standard solution with 13 mL of water, and use this solution as the reference solution. To the test solution and reference solution add 0.3 mL of alkaline mercuric-potassium iodide
TS, cap the test tubes, and allow to stand for about 5 minutes : the test solution does not exhibit a more intense
yellow color than that of the reference solution (not more
than 0.0004%).
(5) Heavy metalsProceed with 1.0 g of Adenosine
according to Method 2 and perform the test. Prepare the
control solution with 1.0 mL of standard lead solution
(not more than 10 ppm).
(6) Related substancesWeigh accurately 25 mg of
Adenosine and dissolve in mobile phase and add to
make exactly 25 mL and use this solution as the test solution. Perform the test with exactly with 20 L of the
test solution as directed under Liquid Chromatography
according to the following conditions, and determine the
percentage of each impurity in the portion of Adenosine
taken by the peak area percentage method: not more than
0.2% of adenine is found; and not more than 0.5% of total impurities is found.
Purity (1) Acidity or alkalinitySuspend 1 g of Adenosine in 20 mL carbon dioxide free water. Stir for 30
seconds, and pass through a coarse filter. To each of two
10 mL portions of the filtrate add 0.1 mL of bromocresol
purple TS. Not more than 0.3 mL of 0.01 N sodium hydroxide is required to produce a blue-violet color in one
portion, and not more than 0.1 mL of 0.01 N hydrochloric acid is required to produce a yellow color in the other
portion.
(2) ChlorideSuspend 0.75 g of Adenosine in 15
mL of water. Stir for 30 seconds, pass through a coarse
filter, and use the filtrate as the test solution. Prepare a
chloride standard solution by diluting 1 mL of sodium
chloride solution (231 mg in 1000 mL) with 100 mL of
water. To the test solution and 10 mL of the chloride
standard solution add 1 mLof nitric acid and 1 mL of silver nitrate TS, dilute each solution with water to 40 mL,
and mix. Allow the solutions to stand for 5 minutes, protected from light. When viewed against a dark background, the test solution is not more turbid than the standard solution (not more than 0.007%).
(3) SulfateSuspend 0.75 g of Adenosine in 15 mL
Column: A stainless steel column about 4.6 mm in
octadecylsilanized silica gel for Liquid Chromatography
(5 m in particle diameter).
Mobile phase: A mixture of sulfate buffer and a solution (1 in 10000) of sodium azide (60:40)
Flow rate: 1.5 mL/minute
System suitability
System performance: Weigh accurately each 20
mg of adenosine and 20 mg of inosine and dissolve in
mobile phase to make 100 mL volume. When the procedure is run with 20 L of this solution under the above
operating condition, the resolution between adenosine
and inosine is not less than 9.0 and the symmetry factor
is not more than 2.5.
System repeatability: Weigh 20 mg each of adenosine and inosine, dissolve in mobile phase to make 100
mL. When the test is repeated 5 times with 20 L of this
solution under the above operating conditions, the rela-
Adenosine
NH2
N
HO
O
H
HO
H
OH
C10H13N5O4 : 267.24
Adenosine contains not less than 99.0% and not more
than 101.0% of adenosine (C10H13N5O4), calculated on
the dried basis.
Description Adenosine is a colorless crystalline powder and produces adenine and D-ribose by hydrolysis.
Adenosine is freely soluble in water, sparingly soluble in
hot water, and slightly soluble in ethanol.
Identification Determine the infrared spectra of Adenosine and Adenosine RS, previously dried, as directed
in the paste method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities
of absorption at the same wavenumbers.
Melting Point
Between 233 and 238 C
tive standard deviation of the peak area is not more than
2.0%.
Time span of measurement: Adjust the run time to
at least twice the retention time of the major peak.
Sulfate bufferDissolve 6.8 g of potassium hydrogen sulfate and 3.4 g of tetrabutylammonium hydrogen
sulfate in water, dilute with water to 1000 mL, and mix.
Adjust with 2 N potassium hydroxide to a pH of 6.5.
hours).
Assay Weigh accurately about 0.5 g of Adenosine, previously dried, dissolve in 50 mL of glacial acetic acid
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 26.724 mg of C10H13N5O4
%
Absorbance E11cm
(249 nm): Between 257 and 271
(after drying, 2 mg, ethanol, 100 mL).
%
(292 nm): Between 85 and 95 (after drying, 2
E11cm
mg, ethanol, 100 mL).

D : Between + 136 and
+ 151 (after drying, 0.5 g, chloroform, 50 mL, 100 mm).
Purity Related substancesDissolve 0.1 g of Ajmaline in 10 mL of chloroform and use this solution as the
test solution. Pipet exactly 1 mL of this solution, add
chloroform to make exactly 100 mL and use this solution
as the standard solution. Perform the test with the test solution and the standard solution as directed under the
Thin-layer Chromatography. Spot 10 L each of the test
solution and the standard solution on a plate of silica gel
with fluorescence indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform,
acetone and diethylamine (5 : 4 : 1) to a distance of about
10 cm and air-dry the plate. Examine under ultraviolet
light (main wavelength: 254 nm): any spot other than the
principal spot from the test solution is not more intense
than the spot from the standard solution.
Loss on Drying Not more than 1.0% (0.6 g, in vacuum,
80 C, 3 hours).
Ajmaline
OH
H
H
H
N
N
CH3
H
OH
CH2CH3
H
H
C20H26N2O2: 326.43
Ajmaline, when dried, contains not less than 96.0% and
not more than 101.0% of ajmaline (C20H26N2O2).
Description Ajmaline is a white to pale yellow, crystalline powder, is odorless and has a bitter taste.
Ajmaline is freely soluble in acetic anhydride or in chloroform, sparingly soluble in methanol, in ethanol, in acetone or in ether, and very slightly soluble in water.
Ajmaline dissolves in dilute hydrochloric acid.
Melting pointAbout 195 C (with decomposition).
Identification (1) Dissolve 50 mg of Ajmaline in 5 mL
of methanol and use this solution as the test solution.
Add 3 mL of nitric acid to 1 mL of the test solution: a
deep red color develops.
(2) Spot the test solution of (1) on filter paper and
spray Dragendorff's TS: an orange color develops.
Assay Weigh accurately about 0.3 g of Ajmaline, previously dried, dissolve in 50 mL of acetic anhydride and
50 mL of acetone for nonaqueous titration and titrate
with 0.05 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform
a blank determination and make any necessary correction.
= 16.322 mg of C20H26N2O2
Ajmaline Tablets
Ajmaline Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of ajmaline
(C20H26N2O2: 326.43).
Method of Preparation Prepare as directed under Tablets, with Ajmaline.
Identification (1) Shake a quantity of powdered Ajmaline Tablets, equivalent to 0.10 g of Ajmaline according
to the labeled amount, with 30 mL of chloroform and fil-
KP 9 35
ter. Evaporate the filtrate in a water-bath to dryness. With
the residue, proceed as directed in the Identification under Ajmaline.
(2) Dissolve 10 mg of the residue of (1) in 100 mL of
ethanol. To 10 mL of this solution, add ethanol to make
50 mL and determine the absorption spectrum of the solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 247 nm and 251
nm and between 291 nm and 294 nm and a minimum between 269 nm and 273 nm.
Dissolution Test Perform the test with 1 tablet of Ajmaline Tablets at 100 revolutions per minute according
to Method 2 under the Dissolution Test, using 900 mL of
diluted phosphate buffer solution, pH 6.8, (1 in 2) as the
dissolution solution. Take 20 mL or more of the dissolved solution 60 minutes after start of the test and filter
through a membrane filter with pore size of not more
than 0.8 m. Discard the first 10 mL of the filtrate and
use the subsequent filtrate as the test solution. Separately,
weigh accurately about 28 mg of Ajmaline RS, previously dried in vacuum at 80 C for 3 hours, dissolve in diluted phosphate buffer solution, pH 6.8, (1 in 2) to make
exactly 500 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the
test solution and the standard solution, respectively, at
288 nm as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Ajmaline Tablets in 60 minutes is
not less than 75%.
Dissolution rate (%) with respect to the labeled
amount of ajmaline (C20H26N2O2) = W S AT 1 180
AS
WS : Amount (mg) of Ajmaline RS,

C: Labeled amount (mg) of ajmaline (C20H26N2O2) in
1 tablet.
Assay Weigh accurately and powder, not less than 20
Ajmaline Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.3 g of ajmaline
(C20H26N2O2), add 15 mL of strong ammonia water and
extract with four 25 mL volumes of chloroform. Combine the chloroform extracts, wash with 10 mL of water,
add 5 g of anhydrous sodium sulfate, shake well and filter, wash the container and the residue with two 10 mL
volumes of chloroform and filter. Evaporate the combined filtrate in a water-bath to dryness, dissolve the residue in 50 mL of acetic anhydride and 50 mL of acetone
for nonaqueous titration and titrate with 0.05 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 16.322 mg of C20H26N2O2
Albendazole
N
H3C
S
H
N
OCH 3
N
O
C12H15N3O2S: 265.33
Albendazole, when dried, contains not less than 98.0%
and not more than 102.0% of albendazole (C12H15N3O2S).
Description Albendazole is white to pale yellow
powder.
Albendazole is freely soluble in anhydrous formic acid,
very slightly soluble in ether or methylene chloride and
practically insoluble in ethanol or water.
Identification (1) Perform the test as directed in the
Related substances: the principal spots from the test solution and the standard solution show the same Rf value.
(2) Determine the infrared spectra of Albendazole
and Albendazole RS, previously dried, as directed in the
potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wavenumbers.
Purity Related substancesDissolve 50 mg of Albendazole in 3 mL of glacial acetic acid, add glacial acetic
acid to make 5 mL and use this solution as the test solution. Separately, weigh accurately a portion of Albendazole RS, dissolve in the glacial acetic acid to contain 5
mg per mL and use this solution as the standard solution.
Pipet 1.0 mL of the standard solution, dilute with glacial
acetic acid to make exactly 100 mL and use this solution
as the diluted standard solution. Perform the test with the
these solutions as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution, the standard solution and the diluted standard solution on a plate
of silica gel for thin-layer chromatography. Develop the
plate with a mixture of chloroform, glacial actic acid and
ether (60 : 10 : 10) to a distance of about 15 cm and airdry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot other than the principal spot
from the test solution is not larger and not more intense
than the spot from the standard solution. (not more than
0.5%)
Loss on Drying Not more than 0.5% (105 C, 4 hours).
Assay Weigh accurately about 0.25 g of Albendazole,
previously dried, dissolve in 100 mL of glacial acetic acid, and warm if necessary. After cooling, add 1 drop of
solvent blue 19 in glacial acetic acid solution (1 in 200),
and titrate with 0.1 mol/L perchloric acid VS until the
color of the solution changes to violet. Perform a blank
determination, and make any necessary correction.
= 26.533 mg of C12H15N3O2S.
well and allow to stand for 20 minutes at 40 1 C in a

water-bath. Add 1.0 mL of dilute hydrochloric acid,
shake and allow to stand for 3 hours at 40 1 C. Cool
rapidly to ordinary temperature and filter. Wash the residue with three 10 mL volumes of water, dry in a desiccator (silica gel) for 18 hours and dry at 105 C for 5 hours:
the weight of the residue is 0.50 g to 0.58 g.
tight containers.
Aldioxa
H
N
Albumin Tannate
Albumin Tannate is a compound of tannic acid and a

protein.
The label states the origin of the protein of Albumin
Tannate.
Description Albumin Tannate is a pale brown powder.
Albumin Tannate is odorless, or has a faint, characteristic odor.
Albumin Tannate is practically insoluble in water or in
ethanol.
Albumin Tannate dissolves in sodium hydroxide TS or
sodium carbonate TS with turbidity.
Identification (1) To 0.1 g of Albumin Tannate, add
10 mL of ethanol and heat in a water-bath for 3 minutes
with shaking. After cooling, filter and to 5 mL of the filtrate, add 1 drop of ferric chloride TS: a blue-purple to
bluish black color is produced. On standing, a bluish
black precipitate is produced.
(2) To 0.1 g of Albumin Tannate, add 5 mL of nitric
acid: an orange-yellow color develops.
Purity (1) AcidShake 1.0 g of Albumin Tannate
with 50 mL of water for 5 minutes and filter. To 25 mL
of the filtrate, add 1.0 mL of 0.1 mol/L sodium hydroxide VS and 2 drops of phenolphthalein TS: a red color
develops.
(2) FatsTo 2.0 g of Albumin Tannate, add 20 mL
of petroleum benzine, shake vigorously for 15 minutes
and filter. Evaporate 10 mL of the filtrate on a waterbath: the weight of the residue is not more than 50 mg.
hours).
Digestion Test To 1.00 g of Albumin Tannate, add
0.25 g of saccharated pepsin and 100 mL of water, shake
OAl(OH)2
O
O
Tannalubin
H2N
N
HN
Dihydroxyaluminum Allantoinate C4H7AlN4O5: 218.10

Aldioxa is a condensation product of allantoin and aluminum hydroxide. When dried, Aldioxa contains not less
than 65.3% and not more than 74.3% of allantoin
(C4H6N4O3: 158.12) and not less than 11.1% and not
more than 13.0% of aluminum (Al: 26.98).
Description Aldioxa is a white powder, is odorless and
tasteless.
Aldioxa is practically insoluble in water, in ethanol or in
ether.
Aldioxa dissolves in dilute hydrochloric acid or in dilute
nitric acid.
Identification (1) To 0.2 g of Aldioxa, add 10 mL of
dilute hydrochloric acid, boil for 5 minutes and add 10
mL of a solution of phenylhydrazine hydrochloride (1 in
100). After cooling, mix well with 0.5 mL of potassium
ferricyanide TS and shake with 1 mL of hydrochloric acid: a red color develops.
(2) To 0.2 g of Aldioxa, add 10 mL of dilute hydrochloric acid, dissolve by warming and cool: the solution responds to the Qualitative Tests for aluminum salt.
Purity (1) ChlorideTo 0.10 g of Aldioxa, add 6 mL
of dilute nitric acid, boil to dissolve with shaking for 5
minutes, cool and add water to make 50 mL. Perform the
test using this solution as the test solution. Prepare the
control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.142%).
(2) SulfateTo 0.20 g of Aldioxa, add 6 mL of dilute hydrochloric acid, boil to dissolve with shaking for 5
minutes, cool and add water to make 50 mL. Perform the
control solution with 1.0 mL of 0.005 mol/L sulfuric acid
VS (not more than 0.240%).
(3) NitrateTo 0.10 g of Aldioxa, add carefully 5
KP 9 37
mL of water and 5 mL of sulfuric acid, dissolve by shaking, cool and superimpose 2 mL of ferrous sulfate TS: no
brown ring is produced at the zone of contact.
(4) Heavy metalsTo 1.0 g of Aldioxa, add 3mL of
hydrochloric acid and 3 mL of water, heat gently to boil
with shaking and evaporate in a water-bath to dryness.
To the residue, add 30 mL of water, shake under warming, cool, filter and to the filtrate, add 2 mL of dilute
acetic acid and water to make 50 mL. Perform the test
using this solution as the test solution. Prepare the control solution as follows: to 3 mL of hydrochloric acid add
3 mL of water, evaporate in a water-bath to dryness and
add 2.0 mL of standard lead solution, 2 mL of dilute
acetic acid and water to make 50 mL (not more than 20
ppm).
Aldioxa according to Method 2 and perform the test (not
more than 2 ppm).
hours).
Assay (1) AllantoinWeigh accurately about 0.1 g of
Aldioxa, previously dried, dissolve in 50 mL of dilute
sulfuric acid by heating, cool and add water to make exactly 100 mL. Pipet exactly 10 mL of this solution and
perform the test as directed under the Nitrogen Determination.
Each mL of 0.005 mol/L sulfuric acid VS
= 0.39529 mg of C4H6N4O3
(2) AluminumWeigh accurately about 0.2 g of Aldioxa, previously dried, dissolve carefully in 50 mL of
dilute hydrochloric acid by heating, cool and add dilute
hydrochloric acid to make exactly 100 mL. Pipet exactly
4 mL of this solution, add water to make exactly 25 mL
and use this solution as the test solution. Separately, pipet
a suitable quantity of aluminum standard stock solution,
dilute with water so that each mL of the solution contains
not less than 16.0 g and not more than 64.0 g of aluminum (Al: 26.98) and use this solution as the standard
solution. Perform the test with the test solution and the
standard solution as directed under the Atomic Absorption Spectrophotometry according to the following conditions and calculate the aluminum content of the test solution from the calibration curve obtained from the absorbance of the standard solution.
Gas: Combustible gas- Acetylene.
Supporting gas- Nitrous oxide.
Lamp: An aluminum hollow cathode lamp.
Wavelength: 309.2 nm.
Alfacalcidol
H
CH3
H3C
CH3
CH3
HO
CH2
H
OH
C27H44O2 : 400.64
Alfacalcidol contains not less than 97.0% and not more
than 102.0% of alfacalcidol (C27H44O2).
Description Alfacalcidol is a white crystals.
Alfacalcidol is freely soluble in ethanol, soluble in fatty
oils, and practically insoluble in water. Alfacalcidol is
sensitive to air, heat and light.
A reversible isomerisation to pre-alfacalcidol takes place
in solution, and the activity is due to both compounds.
Identification (1) Determine the infrared spectra of Alfacalcidol and Alfacalcidol RS, previously dried, as directed in the potassium bromide disk method under the
Infrared Spectrophotometry, respectively: both spectra
(2) Examine the chromatograms obtained in the assay.
The principal peak in the chromatogram obtained with
the test solution is same in retention time as the principal
peak in the chromatogram obtained with standard solution (1).
Purity Related substancesExamine by liquid chromatography as described under Assay. Calculate the percentage content of related substances, other than prealfacalcidol, that are eluted within twice the retention
time of alfacalcidol from the areas of the peaks in the
chromatogram obtained with the test solution by the
normalisation procedure. The content of any individual
related substance is not more than 0.5% and the total area
of all the related substances is not more than 1.0%. Disregard any peak not more than 0.1%.
Assay Carry out the assay as rapidly as possible, avoiding exposure to light and air. Weigh accurately about 1.0
mg of Alfacalcidol, dissolve in mobile phase to make exactly 10 mL and use this solution as the test solution.
Separately, weigh accurately 1.0 mg of Alfacalcidol RS
and dissolve in mobile phase without heating to make
exactly 10 mL and use this solution as the standard solution (1). To 1.0 mL of the standard solution (1) add mobile phase to make exactly 100 mL and use this solution
as the standard solution (2). Heat 2 ml of the standard solution (1) in a water-bath at 80 C under a reflux condenser for 2 hours and cool and use this solution as the
standard solution (3). Perform the test with 100 L each
of the test solution and the standard solutions (1) and (2)
as directed under Liquid Chromatography according to
the following conditions, and determine each peak area,
AT and AS of alfacalcidol, by the automatic integration method.
Description Alfuzosin Hydrochloride is a white crystalline powder.

Alfuzosin Hydrochloride is freely soluble in water, sparingly soluble in ethanol, and practically insoluble in
dichloromethane.
Alfuzosin Hydrochloride is hygroscopic.
Amount (mg) of alfacalcidol (C27H44O2)
Identification (1) Determine the infrared spectra of Alfuzosin Hydrochloride and Alfuzosin Hydrochloride RS,
previously dried, as directed in the potassium bromide
disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) To 0.5 g of Alfuzosin Hydrochloride add 25 mL
of water. The diluted solution of 1 mL of this solution by
1 mL of water responds to the Qualitative Tests (2) for
chlorides.
= amount (mg) of Alfacalcidol RS
AT
AS
Column: A stainless steel column about 4 mm in inside diameter and about 25 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (5
Mobile phase: the mixture of acetonitrile, water and 9
mol/L ammonia water (800 : 200 : 1).
System suitability
operating condition, the retention time for prealfacalcidol, relative to alfacalcidol, is about 1.3 with the
resolution between the peaks due to pre-alfacalcidol and
alfacalcidol being not less than 4.0
above operating conditions, the relative standard deviation of the peak areas of alfacalcidol is not more than
1.0%.
Packaging and Storage Preserve in a tight container,
under nitrogen, protected from light, at a temperature of
2 C to 8 C. The contents of an opened container are to
be used immediately.
Alfuzosin Hydrochloride
CH3
H3CO
H
H
N
O
HCl
N
H3CO
NH2
and enantiomer
C19H27N5O4HCl : 425.91
Alfuzosin Hydrochloride contains not less than 98.5%
and not more than 101.0% of alfuzosin hydrochloride
(C19H27N5O4HCl), calculated on the anhydrous basis.
pH The pH of the solution of 0.5 g of Alfuzosin Hydrochloride in 25 mL of water is between 4.0 and 6.0.
D : Between -0.10 and
+0.10 (calculated on the anhydrous basis, 0.2 g, water,
10 mL, 100 mm)
Purity Related substancesWeigh accurately 20.0
mg of Alfuzosin Hydrochloride, dissolve in mobile phase
to make exactly 100 mL and use this solution as test solution. Pipet exactly 1.0 mL of the test solution, add mobile phase to make exactly 50 mL, pipet 5.0 mL of this
solution, add mobile phase to make exactly 20 mL and
use this solution as the standard solution (1). Separately,
weigh accurately 5 mg of Alfuzosin Impurity I {N-[3[(4-Amino-6,7-dimethoxyquinolin-2-yl)(methyl)amino]
propyl]furan-2-carboxamide} RS, dissolve in mobile
phase to make 25 mL, pipet exactly 1 mL of this solution,
add 1 mL of the test solution and then add mobile phase
to make exactly 100 mL and use this solution as the
standard solution (2). Perform the test with exactly 20 L
each of the test and the standard solution (2) as directed
under Liquid Chromatography according to the following conditions, and determine each peak area by the automatic integration method: the area of any peak other
than the principal peak from the test solution is not
greater than 0.6 times the area of the principal peak from
the standard solution (1) (0.3%); the total area of all
peaks other than the principal peak is not greater than the
area of the principal peak with the standard solution (1)
(0.5%). Disregard any peak with an area less than 0.025
times that of the principal peak from the standard solution (1).
KP 9 39
Mobile phase: The mixture of sodium perchlorate solution, acetonitrile and tetrahydrofuran (80 : 20 : 1).
System suitability
System performance: Perform the test with 20 l
of standard solution (2) according to the above conditions. Adjust the sensitivity of the system so that the
height of the two peaks in the chromatogram obtained is
at least 50% of the full scale of the recorder. The test is
not valid unless the resolution between the peaks corresponding to alfuzosin and alfuzosin related substance I is
at least 3.0.
Sodium perchlorate solutionMix 5 mL of perchloric acid and 900 mL of water, adjust pH to 3.5 with
8.5w/v% sodium hydroxide VS and add water to make
1000 mL.
Water Not more than 2.0% (0.5 g, volumetric titration,
direct titration)
Assay Weigh accurately about 0.3 g of Alfuzosin Hydrochloride, dissolve in the mixture of 40 mL of glacial
acetic acid and 40 mL of acetic anhydride and titrate
= 42.59 mg of C19H28ClN5O4.
tight containers.
Preserve in light-resistent,
Alimemazine Tartrate
(1 in 50) is between 5.0 and 6.5.

Alimemazine Tartrate is gradually colored by light.
Identification (1) To 2 mL of a solution of Alimemazine Tartrate (1 in 100), add 1 drop of ferric chloride TS:
a red-brown color is produced and immediately a yellow
precipitate is formed.
(2) Dissolve 1 g of Alimemazine Tartrate in 5 mL of
water, add 3 mL of sodium hydroxide TS, extract with
two 10 mL volumes of ether [use the aqueous layer obtained in the Identification (4)]. Shake the combined ether extracts with 3 g of anhydrous sodium sulfate, filter
and evaporate the ether with the aid of a current of air.
Dry the residue in a desiccator (in vacuum, P2O5) for 16
hours: it melts between 66 C and 70 C.
(3) Determine absorption spectra of solutions of Alimemazine Tartrate and Alimemazine Tartrate RS, in water (1 in 100000) as directed under the Ultraviolet-visible
(4) The aqueous layer, obtained in the Identification
(2), when neutralized with dilute acetic acid, responds to
the Qualitative Tests (1) and (2) for tartrate.
Melting Point
Purity (1) Clarity and color of solution Dissolve

1.0 g of Alimemazine Tartrate in 20 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Alimemazine Tartrate according to Method 2 and perform the test.
Alimemazine Tartrate according to Method 3 and perform the test. Use a solution of magnesium nitrate in
ethanol (1 in 5) (not more than 2 ppm).
hours).
CH3
CH3
CH2CHCH2N
CH(OH)CO 2H
CH3
N
CH(OH)CO 2H
(C18H22N2S)2C4H6O6 : 746.98
Alimemazine Tartrate, when dried, contains not less than
98.0% and not more than 101.0% of alimemazine tartrate
(C18H22N2S)2 C4H6O6).
Description Alimemazine Tartrate is a white powder,
is odorless and has a bitter taste.
Alimemazine Tartrate is freely soluble in water or in glacial acetic acid, sparingly soluble in ethanol, and practically insoluble in ether.
pH The pH of a solution of Alimemazine Tartrate

Assay Weigh accurately about 0.8 g of Alimemazine
Tartrate, previously dried, dissolve in 50 mL of glacial
acetic acid and titrate with 0.1 mol/L perchloric acid VS
until the color of the solution changes from red through
brown to green-brown (indicator: 2 mL of naphtholbenzeine TS). Perform a blank determination
and make any necessary correction.
= 37.349 mg of (C18H22N2S)2C4H6O6
tight containers.
Allantoin
O
NH2
NH
HN
NH
C4H6N4O3 : 158.12
Allantoin, when dried, contains not less than 98.5% and
not more than 101.0% of allantoin (C4H6N4O3).
Description Allantoin is a white crystalline powder.
Allantoin is slightly soluble in water and very slightly soluble in ethanol.
Allantoin dissolves in sodium hydroxide TS.
Melting Point About 225 C (decomposition)
make exactly 10 mL and use this solution as test solution

(1). Pipet 1 mL of the test solution (1), add a mixture of
methanol and water (1:1) to make exactly 10 mL and use
this solution as the test solution (2). Separately, weigh
accurately about 10 mg of Allantoin RS, add a mixture of
methanol and water (1 : 1) to make exactly 10 mL and
use this solution as the standard solution (1). Weigh accurately about 10 mg of urea RS, add water to make exactly 10 mL, pipet 1 mL of this solution, add methanol to
make exactly 10 mL and use this solution as the standard
solution (2). Mix 1 mL each of the standard solution (1)
and the standard solution (2) and use this solution as the
standard solution (3). Perform the test with these solutions as directed under the Thin-layer Chromatography.
Spot 10 L of the test solution (1) and 5 L each of the
test solution (2), the standard solution (1), the standard
solution (2) and the standard solution (3) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of 1-butanol,
water and glacial acetic acid (60 : 25 : 15) to a distance
of about 10 cm and air-dry the plate. Spray evenly the
plate with a solution of 0.1 g dimethylaminobenzaldehyde in 20 mL of a mixture of methanol and hydrochloric acid (3 : 1). Dry the plate in a current of hot air. Examine under daylight after 30 min: any spot frorm the
test solution (1), other than the principal spot, is not more
intense than the spot from standard solution (2) (0.5%).
The test is not valid unless the chromatogram from standard solution (3) shows two clearly separated principal
spots.
Identification (1) Boil 20 mg with a mixture of 1 mL

of 2 mol/L sodium hydroxide TS and 1 mL of water. Allow to cool. Add 1 mL of 2 mol/L hydrochloric acid TS.
To 0.1 mL of the solution add 0.1 mL of a solution of potassium bromide (1 in 10), 0.1 mL of a solution of resorcinol (1 in 50) and 3 mL of sulfuric acid. Heat for 5 min
to 10 min on a water-bath. A dark blue color develops,
which becomes red after cooling and pouring into about
10 mL of water.
(2) Determine the infrared spectra of Allantoin and
Allantoin RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) The principal spots in the chromatograms obtained with test solution (2) and the standard solution (1)
in Related substances under Purity have the same Rf
values.
Loss on Drying Not more than 0.1% (2 g, 105 C,

constant mass).

+0.10 (0.2 g, water, 20 mL, 100 mm)

= 15.812 mg of C4H6N4O3
Purity (1) Acidity or alkalinityTo a 10 mL solution

of about 50 mg of Allantoin in carbon dioxide-free water,
add 0.1 mL of methyl red TS and 0.2 mL of 0.01 mol/L
sodium hydroxide TS: the solution is yellow. Add 0.4
mL of 0.01 mol/L hydrochloric acid TS: the solution is
red.
(2) Reducing substancesMix 1.0 g of Allantoin
with 10 mL of water by shaking for 2 minutes and filter.
Add 1.5 mL of 0.02 mol/L potassium permanganate TS:
the solution must remain violet for at least 10 min.
(3) Potassium permangate Related substances
Weigh accurately about 0.10 g of Allantoin, dissolve in 5
mL of water with heating. After cool add methanol to
Packaging and Storage Preserve in well-closed containers

Assay Weigh accurately about 1.2 g of Allantoin, previously dried, add 40 mL of water to dissolve. Titrate
with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
Allopurinol
N
H
N
N
OH
C5H4N4O: 136.11
KP 9 41
Allopurinol, when dried, contains not less than 98.0%

and not more than 101.0% of allopurinol (C5H4N4O).
Description Allopurinol is a white to pale yellowish
white crystal or crystalline powder and is odorless.
Allopurinol is slightly soluble in dimethylformamide,
very slightly soluble in water, and practically insoluble in
ethanol or in ether.
Allopurinol dissolves in sodium hydroxide TS or in ammonia TS.
Melting pointNot lower than 320 C (with decomposition)
Identification (1) Dissolve 0.1 g of Allopurinol in 50
mL of water by warming. To 5 mL of this solution, add 1
mL of ammonia TS and 1 mL of silver nitrate TS: a
white precipitate is produced.
(2) Determine the absorption spectra of solutions of
Allopurinol and Allopurinol RS, in water (1 in 200000)
as directed under Ultraviolet-visible Spectrophotometry:
the same wavelengths.
(3) Determine the infrared spectra of Allopurinol and
Allopurinol RS as directed in the potassium bromide disk
method under the Infrared Spectrophotometry: both
spectra exhibit similar intensities of absorption at the
same wavenumbers.
g of Allopurinol in 10 mL of sodium hydroxide TS: the
solution is clear and has no more color than Color
Matching Fluid D.
(2) SulfateTo 2.0 g of Allopurinol, add 100 mL of
water and boil for 5 minutes. Cool, add water to make
100 mL and filter. To 25 mL of the filtrate, add 1 mL of
dilute hydrochloric acid and water to make 50 mL and
perform the test using this solution as the test solution.
Prepare the control solution with 0.40 mL of 0.005 mol/L
sulfuric acid VS (not more than 0.038%).
(3) Heavy metalsProceed with 1.0 g of Allopurinol
Allopurinol according to Method 3 and perform the test
(5) Related substancesDissolve 50 mg of Allopurinol in 10 mL of ammonia TS and use this solution as
the test solution. Pipet exactly 1 mL of this solution, add
ammonia TS to make exactly 200 mL and use this solution as the standard solution. Perform the test with the
test solution the standard solution as directed under the
solution and the standard solution on a plate of cellulose
with fluorescent indicator for thin-layer chromatography.
Develop the plate with ammonia TS saturated with nbutanol to a distance of about 10 cm and air-dry the plate.
Examine under ultraviolet light (main wavelength: 254
nm): any spot other than the principal spot from the test
solution is not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately about 0.16 g of Allopurinol,
previously dried, dissolve in 70 mL of dimethylformamide by warming. Cool and titrate with 0.1 mol/L tetramethylammonium hydroxide VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). Separately to
70 mL of dimethylformamide, add 12 mL of water, perform a blank determination with this solution and make
any necessary correction.
Each mL of 0.1 mol/L tetramethylammonium
hydroxide VS = 13.611 mg of C5H4N4O
Allopurinol Tablets
Allpurinol Tablets contain not less than 93.0% and not
more than 107.0% of the labeled amount of allopurinol
(C5H4N4O : 136.11).
Method of Preparation Prepare as directed under Tablets, with Allopurinol.
Identification To a quantity of powdered Allopurinol
Tablets, equivalent to 50 mg of Allopurinol according to
the labeled amount, add 10 mL of 0.1 mol/L sodium hydroxide VS, mix thoroughly and extract. After filtration,
make the filtrate acidic with 1 mol/L acetic acid. Collect
the precipitate, wash few times with 3 mL of dehydrated
ethanol, 4 mL of anhydrous ether, dry in air for 15 minutes and dry at 105 C for 3 hours. Determine the infrared spectra of the residue and Allopurinol RS as directed
in the potassium bromide disk method under the Infrared
Dissolution Test Perform the test with 1 tablet of Allopurinol Tablets at 75 revolutions per minute according to
Method 2 under the Dissolution Test, using 900 mL of
0.1 mol/L hydrochloric acid as the dissolution solution.
Take a volume of the dissolved solution 45 minutes after
starting the test and filter through a membrane filter, dilute with dissolution solution and use this solution as the
test solution. Separately, weigh accurately a portion of
Allopurinol RS, dissolve in the dissolution solution to
make the same concentration with the test solution and
use this solution as the standard solution. Determine the
absorbances, AT and AS , of the test solution and the

standard solution, respectively, at approximately 250 nm
as directed under the Ultrviolet-visible Spectrophotometry.
The dissolution rate of Allopurinol Tablets in 45 minutes
should be not less than 75%.
tablets of Allopurinol Tablets. Weigh accurately a portion
of the powder, equivalent to about 50 mg of allopurinol
(C5H4N4O), add exactly 10 mL of 0.1 mol/L sodium hydroxide VS, shake for 10 minutes and add water to make
exactly 50 mL (perform the following assay as soon as
possible). After centrifugation, discard 10 mL of the first
filtrate, collect exactly 4 mL of the subsequent filtrate,
add exactly 2.0 mL of the internal standard solution and
the mobile phase to make exactly 200 mL and use this
solution as the test solution. Separately, weigh accurately
about 50 mg of Allopurinol RS, previously dried at 105
C in vacuum for 5 hours, dissolve in 10 mL of 0.1
mol/L sodium hydroxide VS, mix in shaker for 10 minutes and add water to make exactly 50 mL. To exactly 4
mL of this solution, add exactly 2 mL of the internal
standard solution and the mobile phase to make 200 mL
and use this solution as the standard solution (prepare
freshly when used). Perform the test with 15 L each of
the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of
the peak area of Allopurinol to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of allopurinol (C5H4N4O)
= amount (mg) of Allopurinol RS QT
QS
Internal standard solutionA solution of 50 mg of

hypoxantin and 10 mL of 0.1 mol/L sodium hydroxide
VS, mix in shaker, add water to make exactly 50 mL.
Prepare freshly when used.
Column: A stainless steel column, about 4 mm in inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 - 10
Mobile phase: 0.05 mol/L dibasic ammonium phosphate solution.
System suitability
System performance: When procedure is run with
15 L of the standard solution under the above operating

conditions. Hypoxanthin and allopurinol are eluted in
this order with the resolution between their peaks being
not less than 5.
times with 15 L of the standard solution, the relative
standard deviation of the ratios of the peak area of alloprinol to that of internal standard is not more than 3.0%.
Alprazolam
H3C
N
N
N
Cl
C17H13ClN4: 308.77
Alprazolam, when dried, contains not less than 98.5%
and not more than 101.0% of alprazolam (C17H13ClN4).
Description Alprazolam is a white crystal or crystalline powder.
Alprazolam is freely soluble in chloroform, soluble in
methanol or in ethanol, sparingly soluble in acetic anhydride, and practically insoluble in water.
Alprazolam dissolves in dilute nitric acid.
Identification (1) Determine the absorption spectrum
of a solution of Alprazolam in ethanol (1 in 200000) as
directed under the Ultraviolet-visible Spectrophotometry:
it exhibits maximum at around 222 nm.
(2) Dissolve 50 mg of Alprazolam in 0.7 mL of deuterochloroform for nuclear magnetic resonance spectroscopy, and determine the spectrum of this using tetramethylsilane for nuclear magnetic resonance spectroscopy
as an internal reference compound, as directed under the
Nuclear Magnetic Resonance Spectroscopy (1H): it exhibits singlet signal A at around 2.6 ppm, doublet signals
B and C at around 4.0 ppm and 5.4 ppm, and a broad
signal D between 7.1 ppm and 7.96 ppm. The ratio of
integrated intensity of each signal, A : B : C : D, is about
3 : 1 : 1 : 8.
(3) Perform the test with Alprazolam as directed under the Flame Coloration Test (2): a green color appears.
Purity (1) ChlorideDissolve 0.5 g of Alprazolam in
10 mL of dilute nitric acid, add water to make 50 mL,
KP 9 43
and use this solution as the test solution. Prepare the control solution with 0.20 mL of 0.01 mol/L hydrochloric
acid VS (not more than 0.014%).
(2) Heavy metalsProceed with 2.0 g of Alprazolam
according to Method 4, and perform the test. Prepare the
(3) Related substancesDissolve 50 mg of Alprazolam in 10 mL of methanol and use this solution as the
test solution. Pipet exactly 1 mL of this solution, add methanol to make exactly 100 mL, then pipet exactly 1 mL
of this solution, add methanol to make exactly 10 mL
the test with these solutions as directed under the Thinlayer Chromatography. Spot 20 L each of the test solution and the standard solution on a plate of silica gel with
fluorescent indicator for thin-layer chromatography. Develop the plates with an upper layer of a mixture of acetone, hexane, ethyl acetate and ethanol (4 : 2 : 2 : 1) to a
distance of about 10 cm, and air-dry the plates. Examine
under ultraviolet light (main wavelength: 254 nm): any
spot other than principal spot from the test solution is not
more intense than the spot from the standard solution.
Assay Weigh accurately about 0.25 g of Alprazolam,
previously dried, dissolve in 100 mL of acetic anhydride,
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any necessary correction.
= 15.438 mg of C17H13ClN4
Alprenolol Hydrochloride
OH
CH3
OCH2CCH2NHCH
CH2CH
H
CH2
HCl
CH3
and enantiomer
C15H23NO2HCl: 285.81
Alprenolol Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of alprenolol hydrochloride (C15H23NO2HCl).
Description Alprenolol Hydrochloride is a white crys-
tal or crystalline powder.

Alprenolol Hydrochloride is freely soluble in water, in
ethanol, or in glacial acetic acid, slightly soluble in acetic
anhydride, and practically insoluble in ether.
Identification (1) To 2 mL of a solution of Alprenolol
Hydrochloride (1 in 100), add 50 L of cupric sulfate TS
and 2 mL of sodium hydroxide TS: a blue-purple color is
observed. To this solution, add 1 mL of ether, shake well
and allow to stand: a red-purple color is observed in the
ether layer.
(2) Dissolve 50 mg of Alprenolol Hydrochloride in 5
mL of water, add 1 to 2 drops of bromine TS and shake:
the color of the test solution disappears.
(3) Determine absorption spectra of solutions of Alprenolol Hydrochloride, and Alprenolol Hydrochloride
RS, in ethanol (1 in 10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
similar intensities of absorption at the same wavelengths.
(4) Determine the infrared spectra of Alprenolol Hydrochloride and Alprenolol Hydrochloride RS, previously dried, as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(5) A solution of Alprenolol Hydrochloride (1 in 50)
pH Dissolve 1.0 g of Alprenolol Hydrochloride in 10
mL of water: the pH of the solution is between 4.5 and
6.0.
g of Alprenolol Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Alprenolol
Hydrochloride according to Method 2 and perform the
test. Prepare the control solution with 2.0 mL of standard
lead solution (not more than 10 ppm).
Alprenolol Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.10 g of Alprenolol Hydrochloride in 10 mL of ethanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution and add ethanol to make exactly 100 mL. Pipet
exactly 2.5 mL of this solution, add ethanol to make exactly 10 mL and use this solution as the standard solution.
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, acetone, glacial acetic acid and water (60 :
42 : 5 : 3) to a distance of about 10 cm, air-dry the plate
and then dry at 80 C for 30 minutes. After cooling, allow the plate to stand in iodine vapor for 30 minutes: any
spot other than the principal spot and the spot on the
starting point from the test solution are not more intense
Loss on Drying Not more than 0.5% (1 g, silica gel, in
vacuum, 4 hours).
Assay Weigh accurately about 0.5 g of Alprenolol Hydrochloride, previously dried, dissolve in 50 mL of a
mixture of acetic anhydride and glacial acetic acid (7 : 3)
= 28.581 mg of C15H23NO2.HCl
Alprostadil
O
H
OH
CH3
H
OH
Prostaglandin E1
OH
C20H34O5 : 354.48
Alprostadil, when dried, contains not less than 97.0%

and not more than 103.0% of alprostadil (C20H34O5).
Description Alprostadil is a white crystals or crystalline powder.
Alprostadil is freely soluble in dehydrated ethanol or tetrahydrofuran, slightly soluble in acetonitrile, and practically insoluble in water.
Identification (1) To 10 mL each of the solutions of
Alprostadil and Alprostadil RS, respectively, in dehydrated ethanol (1 in 100000) add 1 mL of potassium hydroxideethanol TS and allow to stand for 15 minutes.
Determine the absorption spectra of the solutions as directed under Ultraviolet-visible Spectrophotometry: both
same wavelengths.
(2) Determine the infrared spectra of Alprostadil and
Alprostadil RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar

D : Between -53 and 61 (after drying, 25 mg, tetrahydrofuran, 5 mL, 100
mm)
Melting Point
Purity Related substancesDissolve 4 mg of Alprostadil in 2 mL of a mixture of acetonitrile and water (9 : 1)

and use this solution as the test solution. Pipet exactly
0.5 mL of this solution, add a mixture of acetonitrile and
water (9 : 1) to make exactly 10 mL, pipet exactly 2.0
mL of this solution, add a mixture of acetonitrile and water (9 : 1) to make exactly 10 mL and use this solution as
the standard solution. Perform the test with exactly 5 L
each of the test solution and the standard solutions as directed under Liquid Chromatography according to the
following conditions, and determine each peak area by
the automatic integration method: the areas of the peaks
being about 0.70 and about 1.26 in relative retention time
reference to the peak of alprostadil in the test solution are
not larger than 0.5 times the peak area of alprostadil obtained with the standard solution; the areas of the peaks
being about 0.88 and about 1.18 in relative retention time
reference to alprostadil in test solution are not larger than
the peak area of alprostadil obtained with the standard
solution; the area of the peaks other than alprostadil and
above mentioned peaks in the test solution is not larger
than 0.1 times the peak area of alprostadil in standard solution. The total area of all peaks other than alprostadil is
not larger than 2 times the peak area of alprostadil from
the standard solution.
Detector, column, column temperature, mobile phase,
flow rate: Perform as directed in the operating conditions
in the Assay.
System suitability
Test for required detectability: Pipet 2 mL of the
standard solution, add a mixture of acetonitrile and water
(9 : 1) to make 20 mL. Confirm that the peak area of alprostadil obtained with 5 L of this solution is equivalent
to 7 to 13% of that with 5 L of the standard solution.
System performance: Perform as directed in the
system suitability in the Assay.
the peak area of alprostadil is not more than 1.5%.
as the retention time of alprostadil beginning after the
solvent peak.
phosphorus (V) oxide, 4 hours).
Assay Weigh accurately about 5 mg each of Alprostadil and Alprostadil RS, previously dried, to each add exactly 5 mL of internal standard solution to dissolve, add a
mixture of acetonitrile and water (9 : 1) to make exactly
KP 9 45
50 mL, and use the solutions as test solution and standard
solution, respectively. Perform the test with 5 L of the
test solution and the standard solution as directed under
the Liquid Chromatography according to the following
conditions and calculate the ratios, QT and QS , of the
peak area of alprostadil to that of the internal standard
for the test solution and the standard solution, respectively.
Amount (mg) of alprostadil (C20H34O5)
= amount (mg) of Alprostadil RS
QT
QS
Internal standard solutionA solution of dimethyl

phthalate in a mixture of acetonitrile and water (9 : 1) (1
in 10000).
about 40 o C .
Mobile phase: Dissolve 9.07 g of potassium dihydrogen phosphate in water to make 1000 mL, add the solution prepared by dissolving 9.46 g of potassium monohydrogen phosphate in water to make 1000 mL to adjust
pH to 6.3. Dilute this solution 10 times with water. To
360 mL of this solution add 110 mL of acetonitrile and
30 mL of methanol and mix.
time of alprostadil is about 10 minutes.
System suitability
System performance: When the prodedure is run
with 5 L of the standard solution, as diredcted under the
above operating, alprostadil and the internal standard are
peaks being not less than 9.
times with 5 L of the standard solution, as directed under the above conditions, relative standard deviation of
the ratios of the peak area of alprostadil reference to the
internal standard is not more than 1.0%.
Packaging and Storage Preserve in light-resistant,
tight containers. Store at below 5 C.
Aluminum Hydroxide Gel

AI(OH)3: 78.00
Aluminum Hydroxide Gel is a suspension of aluminum
hydroxide. Aluminum Hydroxide Gel contains not less

than 3.6% and not more than 4.4% of the labeled amount
of aluminum oxide (Al2O3: 101.96) when analyzed as
aluminum hydroxide suspension. Aluminum Hydroxide
Gel may contain peppermint oil, glycerin, sorbitol, sucrose, saccharin, or other suitable flavors and suitable antimicrobial agents.
Description Aluminum Hydroxide Gel is a white,
viscous suspension. A volume of water layer is separated
on standing.
Identification Dissolve approximately 5 mL of Aluminum Hydroxide Gel in 10 mL of dilute hydrochloride acid and warm: the solution responds to Qualitative Tests
for aluminum salt.
pH Between 5.5 and 8.0.
Purity (1) ChlorideTransfer an accurately measured
volume of Aluminum Hydroxide Gel, equivalent to 10 g
of Al(OH)3, to a porcelain dish. Add 0.1 mL of potassium
chromate TS and 25 mL of water. Stir and add 0.10
mol/L of silver nitrate until a faint, persistent pink color
is obtained: not more than 8.0 mL of 0.10 mol/L nitrate is
required (not more than 0.28%).
(2) SulfateAdd 5.0 mL of 3 mol/L of hydrochloric
acid to an accurately measured volume of Aluminum
Hydroxide Gel, equivalent to 5 g of Aluminum Hydroxide Gel and heat to dissolve. Cool, dilute with water to
make 250 mL and filter, if necessary. Add 1 mL of dilute
hydrochloric acid to a 20 mL portion of the filtrate, dilute
with water to make 50 mL and use this solution as the
test solution. 0.40 mL of 0.005 mol/L sulfuric acid are
added to reference standard (not more than 0.05%).
(3) ArsenicAdd 10 mL of dilute sulfuric acid to 1.2
g of Aluminum Hydroxide Gel, shake, heat to boiling
and cool. Dilute with water to make 20 mL and filter.
Use 10 mL of the filtrate as the test solution. Perform the
test (not more than 0.6 ppm).
(4) Heavy metalAdd 5 mL of dilute hydrochloric
acid to 5.0 g of Aluminum Hydroxide Gel, shake, heat to
boiling and evaporate in a water-bath to dryness. Add 30
mL of water to the residue, warm, shake, cool and filter.
Add 2 mL of dilute acetic acid and dilute with water to
make 50 mL. Use this solution as the test solution and
perform the test. Evaporate 5 mL of dilute hydrochloric
acid in a water-bath. Add 2.5 mL of the standard lead solution and 2 mL of diluted acetic acid. Dilute with water
to make 50 mL and use this solution as the control solution (not more than 5 ppm).
Test for Acid-Neutralizing Capacity Add about 1.5
mL of Aluminum Hydroxide Gel in a flask equipped
with a stopper, previously weighed. Weigh accurately
and perform the test: The volume of 0.1 mol/L of hydrochloric acid VS consumed is 12.5 to 25.0 mL per g of
Aluminum Hydroxide Gel.
Microbial Limits Its total viable aerobic microbial
count does not exceed 100 per mL and it meets the requirement of the test for the absence of Escherichia coli.
Assay Transfer an accurately measured volume of
Aluminum Hydroxide Gel, equivalent to about 25 g of
Aluminum Hydroxide Gel, to a beaker, add 15 mL of hydrochloric acid and heat gently until solution is clear.
Cool, transfer to a volumetric flask, dilute with water to
make 500 mL and mix. Pipet 20 mL of this solution into
a beaker and add 25.0 mL of disodium ethylenediaminetetraacetate VS and 20 mL of acetic acid ammonium acetate buffer TS, with continuous stirring then heat near the
boiling point for 5 minutes. Cool and add 50 mL of ethanol and 2 mL of dithizone TS. Titrate the solution with
0.05 mol/L of zinc sulfate VS until the color changes
from green-violet to rose-pink. Perform a blank determination, substituting 20 mL of water for the sample and
make any necessary correction.
Each mL of 0.05 mol/L of disodium ethylenediaminetetraacetate VS = 2.5490 mg of Al2O3
Packaging and Storage Preserve in tight containers,
avoiding freezing.
Dried Aluminum Hydroxide Gel

Dried Aluminum Hydroxide gel contains not less than
50.0% of aluminum oxide (Al2O3: 101.96).
Description Dried Aluminum Hydroxide Gel is a
white and amorphous powder. Dried Aluminum Hydroxide gel is odorless and has no taste.
Dried Aluminum Hydroxide Gel is practically insoluble
in water, in ether or in ethanol
Most of Dried Aluminum Hydroxide Gel is soluble in dilute hydrochloric acid or in sodium hydroxide TS.
Identification Dissolve 0.2 g of Dried Aluminum Hydroxide Gel in 20 mL of dilute hydrochloric acid by
warming and centrifuge. The supernatant responds to
Qualitative test for aluminum salt.
Purity (1) Acidity of solutionAdd 1.0 g of Dried
Aluminum Hydroxide Gel in 25 mL of water and centrifuge: the supernatant is neutral.
(2) ChlorideAdd 1.0 g of Dried Aluminum Hydroxide Gel to 30 mL of dilute hydrochloric acid, shake
and heat gently to boiling. Cool, dilute with water to
make 100 mL and centrifuge. Add 6 mL of dilute hydronitric acid to 5 mL of the supernatant and dilute with water to make 50 mL. Use this solution as the test solution.
of hydrochloric acid (not more than 0.284%).
(3) SulfateAdd 1.0 g of Dried Aluminum Hydroxide Gel to 15 mL of dilute hydrochloric acid. shake and
heat gently to boiling. Cool, dilute with water to make

250 mL and centrifuge. Add 1 mL of dilute hydrochloric
acid to 25 mL of the supernatant and dilute with water to
make 50 mL. Use this solution as the test solution. Prepare the control solution with 1.0 mL of 0.005 mol/L of
hydrochloric acid (not more than 0.480%).
(4) NitrateAdd 0.1 g of Dried Aluminum Hydroxide Gel to 5 mL of water. Add 5 mL of sulfuric acid carefully to dissolve, shake and cool. No brown ring is produced when ferric chloride is added drop-wise.
(5) Heavy metalAdd 0.5 g of Dried Aluminum
Hydroxide Gel to 5 mL of dilute hydrochloric acid and
dilute with water to make 50 mL. Use this solution as the
test solution and perform the test. Evaporate 5 mL of dilute hydrochloric acid to dryness. Add 3.0 mL of the
standard lead solution and 2 mL of dilute acetic acid. Dilute with water to make 50 mL (not more than 60 ppm).
(6) ArsenicTo 0.8 g of Dried Aluminum Hydroxide Gel, add 10 mL of dilute sulfuric acid, heat gently to
boil while shaking, cooling and filter. Take 5 mL of the
filtrate, use this solution as the test solution and perform
the test (not more than 5 ppm).
Test for Acid-Neutralizing Capacity Weigh precisely
about 0.2 g of Dried Aluminum Hydroxide Gel in a flask
equipped with a stopper and perform the test: The volume of 0.1 mol/L of hydrochloric acid VS consumed is
not less than 250 mL per 1.0 g of Aluminum Hydroxide
Gel.
Assay Transfer an accurately measured quantity of
Dried Aluminum Hydroxide Gel, equivalent to about 22
g of Aluminum Hydroxide Gel, to a beaker, add 15 mL
of hydrochloric acid and heat gently until solution is
clear. Cool, transfer to a volumetric flask, dilute with water to make 500 mL and mix. Pipet 20 mL of this solution
into a beaker and add 30 mL of 0.05 mol/L disodium
ethylenediaminetetraacetate VS and 20 mL of acetic acid
ammonium acetate buffer TS with continuous stirring,
then heat the solution near the boiling point for 5 minutes.
Cool and add 55 mL of ethanol and 2 mL of dithizone TS.
Titrate the solution with 0.05 mol/L of zinc sulfate VS
until the color changes from pale dark green to pale red.
Perform a blank determination, substituting 20 mL of
water for the sample and make any necessary correction.
Dried Aluminum Hydroxide Gel

Fine Granules
Dried Aluminum Hydroxide Gel Fine Granules contain
not less than 47.0% of aluminum oxide (Al2O3: 101.96).
KP 9 47
Method of Preparation Prepare as directed under

Granules, with Dried Aluminum Hydroxide Gel.
Identification Dissolve 0.2 g of Dried Aluminum Hydroxide Gel in 20 mL of dilute hydrochloric acid by
warming and centrifuge. The supernatant responds to
Qualitative Test for aluminum salt.
Particle Size Distribution Test It meets the requirement.
Test for Acid-Neutralizing Capacity Proceed as directed in the Acid-neutralizing Capacity under Dried
Aluminum Hydroxide Gel: the volume of 0.1 mol/L of
hydrochloric acid VS consumed is not less than 235 mL
per 1.0 g of Aluminum Hydroxide Gel.
Assay Proceed as directed in the Assay under Dried
Aluminum Hydroxide Gel.
Packaging and Storage Preserve in tight containers
Natural Aluminum Silicate

Description Natural Aluminum Silicate is a white or
slightly colored powder, is odorless and tasteless.
Natural Aluminum Silicate is practically insoluble in water, in ethanol or in ether.
Natural Aluminum Silicate, 1 g, dissolves when heated in
20 mL of sodium hydroxide solution (1 in 5), with some
decomposition, leaving a large amount of insoluble substance.
Identification (1) To 0.5 g of Natural Aluminum Silicate, add 3 mL of diluted sulfuric acid (1 in 3), heat until
white fumes evolve, cool, add 20 mL of water and filter.
Render the filtrate slightly acidic with ammonia TS: the
solution responds to the Qualitative Tests for aluminum
salt.
(2) Prepare a bead by fusing dibasic sodium ammonium phosphate on a platinum loop. Place the bead in
contact with Natural Aluminum Silicate and fuse again:
an infusible material appears in the bead, producing,
upon cooling, an opaque bead with a web-like structure.
Purity (1) Acidity or alkalinityShake 5.0 g of Natural Aluminum Silicate with 100 mL of water and centrifuge: the supernatant liquid so obtained is neutral.
(2) ChlorideTo 5.0 g of Natural Aluminum Silicate,
add 100 mL of water, boil gently for 15 minutes while
shaking, then cool, add water to restore the original volume and centrifuge. To 10 mL of the supernatant liquid,
add 6 mL of dilute nitric acid, dilute to 50 mL with water
and perform the test with this solution with 0.30 mL of

0.01 mol/L hydrochloric acid VS (not more than 0.021%).
(3) SulfateTo the residue obtained in (6), add 3 mL
of dilute hydrochloric acid, heat on a water-bath for 10
minutes, dilute with 50 mL of water and filter. To 2.0 mL
of the filtrate, add 1 mL of dilute hydrochloric acid and
water to make 50 mL. Perform the test with this solution
as the test solution. Prepare the control solution with 1.0
mL of 0.005 mol/L sulfuric acid VS (not more than
0.480%).
(4) Heavy metalsTo 1.5 g of Natural Aluminum Silicate, add 50 mL of water and 5 mL of hydrochloric acid,
boil gently for 20 minutes while shaking, then cool, centrifuge, remove the supernatant liquid, wash the residue
with two 10 mL volumes of water, centrifuging each time,
combine these washings with the filtrate and add strong
ammonia water drop-wise until a precipitate just produces. Add dilute hydrochloric acid drop-wise with vigorous
shaking and redissolve the precipitate. Heat the mixture
with 0.45 g of hydroxylamine hydrochloride, cool and
add 0.45 g of sodium acetate, 6 mL of dilute acetic acid
and water to make 150 mL. Perform the test with 50 mL
of this solution as the test solution. Prepare the control
solution with 2.0 mL of standard lead solution, 0.15 g of
hydroxylamine hydrochloride, 0.15 g of sodium acetate,
2 mL of dilute acetic acid and water to make 50 mL (not
more than 40 ppm).
(5) ArsenicTo 1.0 g of Natural Aluminum Silicate,
add 5 mL of dilute hydrochloric acid, heat gently to boil
while shaking well, cool rapidly and centrifuge. Mix the
residue with 5 mL of dilute hydrochloric acid with shaking, centrifuge, then add 10 mL of water to the residue
and repeat the extraction in the same manner. Concentrate the combined extracts in a water-bath to 5 mL, use
this solution as the test solution and perform the test (not
more than 2 ppm).
(6) Soluble saltsEvaporate 50 mL of the supernatant liquid obtained in (1) on a water-bath to dryness and
ignite the residue at 700 for 2 hours: the weight of the
ignited residue is not more than 40 mg.
(7) Fluoride(i) Apparatus: Use a hard glass apparatus as illustrated in the figure. Ground-glass joints may
be used.
The content of fluoride (F) is not more than 0.01%.
hours).
Adsorptive Power To 0.10 g of Natural Aluminum Silicate, add 20 mL of a solution of methylene blue (3 in
2000), shake for 15 minutes, allow to stand for 5 hours at
37 2 C and centrifuge. Dilute 1.0 mL of the supernatant liquid with water to make 200 mL. Place 50 mL of
the solution in a Nessler tube and observe horizontally or
vertically against a white background: the color of the
solution is not more intense than that of the following
control solution.
Control solutionDilute 1.0 mL of a solution of methylene blue (3 in 2000) with water to make 400 mL and
use 50 mL of this solution.
A: Distilling flask of about 300-mL capacity
B: Steam generator of about 1000-mL capacity, add a boiling stone to prevent bumping
C: Condenser
D: Receiver (200-mL volumetric flask)
E: Steam-introducing tube having an inside diameter of
about 8 mm
F, G: Rubber tube with a pinch-coke
H: Thermometer
(ii) Procedure: Transfer 5.0 g of Natural Aluminum Silicate to the distilling flask A with the aid of 20 mL of
water, add about 1 g of glass fiber and 50 mL of diluted purified sulfuric acid (1 in 2) and connect A to
the distillation apparatus, previously washed with
steam through the steam introducing tube E. Connect
the condenser C with the receiver D containing 10 mL
of 0.01 mol/L sodium hydroxide VS and 10 mL of water so that the lower end of C is immersed in the solution. Heat A gradually until the temperature of the solution in A reaches 130 C, then open the rubber tube F,
close the rubber tube G and boil water in the steam
generator B vigorously. Simultaneously, heat A and
maintain the temperature of the solution in A between
135 C and 145 C Adjust the distilling rate to about
10 mL per minute. Collect about 170 mL of the distillate, then stop the distillation, wash C with a small
quantity of water, combine the washings with the distillate, add water to make exactly 200 mL and use this
solution as the test solution. Perform the test with the
test solution as directed in the procedure of determination for fluoride under the Oxygen Flask Combustion
Method. No corrective solution is used in this procedure.
Amount (mg) of fluoride (F: 19.00) in the test solution
= amount (mg) of fluoride in 5 mL of the standard solution
AT
200
AS
V
Synthetic Aluminum Silicate

Description Synthetic Aluminum Silicate is a white
powder, is odorless and tasteless.
Synthetic Aluminum Silicate is practically insoluble in
water, in ethanol or in ether.
Synthetic Aluminum Silicate, 1 g, dissolves when heated
in 20 mL of a solution of sodium hydroxide (1 in 5),
leaving a small amount of insoluble substance.
Identification Proceed as directed in the Identification
under Natural Aluminum Silicate.
Purity (1) Acidity or alkalinityShake 1.0 g of Synthetic Aluminum Silicate with 20 mL of water and centrifuge: the supernatant liquid so obtained is neutral.
(2) ChlorideProceed as directed in the Purity under
Natural Aluminum Silicate.
(3) SulfateTo 2.0 mL of the supernatant liquid obtained in (2), add 1 mL of dilute hydrochloric acid and
0.480%).
(4) Heavy metalsWeigh about 3.0 g of Synthetic
Aluminum Silicate and proceed as directed in the Purity
(4) under Natural Aluminum Silicate. Prepare the control
solution with 3.0 mL of standard lead solution (not more
than 30 ppm).
(5) ArsenicTo 1.0 g of Synthetic Aluminum Silicate, add 10 mL of dilute hydrochloric acid, proceed as
directed in the Purity (5) under Natural Aluminum Silicate (not more than 2 ppm).
KP 9 49
hours).
Test for Acid-Neutralizing Capacity Weigh accurately about 1g of Synthetic Aluminum Silicate, transfer to a
glass-stoppered flask, add 200 mL of 0.1 mol/L hydrochloric acid VS, exactly measured, stopper the flask, and
shake at 37 2 C for 1 hour. Filter, pipet 50 mL of the
filtrate, and titrate by stirring well the excess hydrochloric acid with 0.1mol/L sodium hydroxide VS until the pH
of the solution changes to 3.5. The volume of 0.1 mol/L
hydrochloric acid VS consumed is not less than 50.0 mL
per g of Synthetic Aluminum Silicate.
Amantadine Hydrochloride
NH2
HCl
C10H17NHCl: 187.71
Amantadine Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of amantadine hydrochloride (C10H17NHCl).
Description Amantadine Hydrochloride is a white
crystalline powder, is odorless and has a bitter taste.
Amantadine Hydrochloride is very soluble in formic acid,
freely soluble in water, in methanol or in ethanol and
practically insoluble in ether.
Identification (1) To 0.1 g of Amantadine Hydrochloride, add 1 mL of pyridine and 0.1 mL of acetic anhydride, dissolve by boiling for 1 minute, add 10 mL of dilute hydrochloric acid and cool in ice-water. Filter the
crystals separated, wash with water and dry at 105 C for
1 hour: the residue melts between 147 C and 151 C.
(2) Determine the infrared spectra of Amantadine
Hydrochloride and amantadine hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Amantadine Hydrochloride (1 in 50)
pH Dissolve 1.0 g of Amantadine Hydrochloride in 5
mL of water: the pH of this solution is between 4.0 and
6.0.
g of Amantadine Hydrochloride in 10 mL of water: the
solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Amantadine Hydrochloride according to Method 4 and perform
the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Amantadine Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.50 g of Amantadine Hydrochloride in 10 mL of water, add 10 mL of sodium hydroxide TS and 10 mL of chloroform and shake.
Filter the chloroform layer through absorbent cotton with
3 g of anhydrous sodium sulfate on a funnel and use the
filtrate as the test solution. Pipet exactly 1 mL of the test
solution, add chloroform to make exactly 100 mL and
use this solution as the standard solution. Perform the
test with 2 L each of the test solution and the standard
solution as directed under the Gas Chromatography according to the following conditions. Determine each
peak area of these solutions by the automatic integration
method: the area of each peak other than that of major
peak from the test solution is not larger than 1/3 of the
area of major peak from the standard solution and the total area of all peaks is not larger than the area of major
peak from the standard solution.
Column: A glass column, about 3 mm in inside diameter and about 2 m in length, packed with siliceous
earth for gas chromatography (150 - 180 m in particle
diameter) coated with a mixture of branched hydrocarbon of petroleum hexamethyltetracosane group for gas
chromatography and potassium hydroxide at the ratios of
2% and 1%, respectively.
Column temperature: Inject at a constant temperature
of about 125 C, maintain the temperature for 5 minutes,
raise at the rate of 5 C per minute to 150 C and maintain at a constant temperature of about 150 C for 15 minutes.
Carrier gas: Nitrogen.
time of amantadine is about 11 minutes.
System suitability
System performance: Dissolve 0.15 g of naphthalene in 5 mL of the test solution and add chloroform to
make 100 mL. When the procedure is run with 2 L of
this solution under the above operating conditions, naphthalene and amantadine are eluted in this order with the
resolution between these peaks being not less than 2.5.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of amantadine obtained from 2
L of the standard solution composes about 10% of the
full scale.
Time span of measurement: About twice as long as the
retention time of amantadine after the solvent peak.
hours).
Assay Weigh accurately about 0.2 g of Amantadine
formic acid, add exactly 15 mL of 0.1 mol/L perchloric
acid VS and heat on a water-bath for 30 minutes. After
cooling, add glacial acetic acid to make 70 mL and titrate
the excess perchloric acid with 0.1 mol/L sodium acetate
in Titrimetry). Perform a blank determination and make
= 18.771 mg of C10H17NHCl
Packaging and Storage Preserve in well-closed con-
KP 9 51
10 cm and air-dry the plate. Allow the plate to stand in
the saturated iodine vapor: any spot other than the principal spot from the test solution is not more intense than
the spot from the standard solution.
tainers.
Ambenonium Chloride
Cl
Cl
H2C
CH2CH3
CH2CH2NH
CH2CH3
NHCH2CH2
CH2CH3
CH2
2 Cl

hours).
CH2CH3

C28H42C14N4O2: 608.47
Ambenonium Chloride contains not less than 98.5% and
not more than 101.0% of ambenonium chloride
(C28H42C14N4O2), calculated on the dried basis.
Description Ambenonium Chloride is a white powder,
Ambenonium Chloride is freely soluble in water, in methanol or in glacial acetic acid, soluble in ethanol, and
slightly soluble in acetic anhydride.
Ambenonium Chloride is hygroscopic.
Assay Weigh accurately about 0.3 g of Ambenonium

Chloride and dissolve in 50 mL of a mixture of acetic
anhydride and glacial acetic acid (7 : 3). Titrate with 0.1
mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank
determination and make any necessary correction.
= 30.424 mg of C28H42Cl4N4O2

Identification (1) Determine absorption spectra of the
solutions of Ambenonium Chloride and Ambenonium
Chloride RS, in methanol (1 in 5000) as directed under
the Ultraviolet-visible Spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Ambenonium
Chloride and Ambenonium Chloride RS, previously
dried, as directed in the potassium bromide disk method
under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Ambenonium Chloride (1 in 100)
g of Ambenonium Chloride in 10 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Ambenonium Chloride according to Method 4 and perform the
test. Use a solution of magnesium nitrate in ethanol (1 in
5). Prepare the control solution with 2.0 mL of standard
(3) Related substancesDissolve 0.10 g of Ambenonium Chloride in 10 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution and add methanol to make exactly 20 mL. Pipet
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of n-butanol,
formic acid and water (12 : 6 : 5) to a distance of about
Amidotrizoic Acid
CO2H
I
O
CH3
O
HN
NH
CH3
C11H9I3N2O4: 613.91
Amidotrizoic Acid contains not less than 98.0% and not
more than 101.0% of amidotrizoic acid (C11H9I3N2O4),
calculated on the dried basis.
Description Amidotrizoic Acid is a white, crystalline
powder and is odorless.
Amidotrizoic Acid is slightly soluble in ethanol, very
slightly soluble in water and practically insoluble in ether.
Amidotrizoic Acid dissolves in sodium hydroxide TS.
Identification (1) Heat 0.1 g of Amidotrizoic Acid
over flame: a purple gas is evolved.
(2) Determine the infrared spectra of Amidotrizoic
Acid and amidotrizoic acid RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
1.0 g of Amidotrizoic Acid in 10 mL of 0.2 mol/L sodium hydroxide TS: the solution is clear and colorless.
(2) Primary aromatic aminesDissolve 0.20 g of
Amidotrizoic Acid in 5 mL of water and 1 mL of sodium
hydroxides TS, add 4 mL of a solution of sodium nitrite
(1 in 100) and 10 mL of 1 mol/L hydrochloric acid TS,
shake and allow to stand for 2 minutes. Add 5 mL of
ammonium sulfamate TS, shake well, allow to stand for
1 minute and add 0.4 mL of a solution of -naphthol in
ethanol (1 in 10), 15 mL of sodium hydroxide TS and
water to make exactly 50 mL. Determine the absorbance
of this solution at 485 nm using a solution, prepared in
the same manner, as the blank: the absorbance is not
more than 0.15.
(3) Soluble halidesDissolve 2.5 g of Amidotrizoic
Acid in 20 mL of water and 2.5 mL of ammonia TS, add
20 mL of dilute nitric acid and water to make 100 mL,
allow to stand for 15 minutes with occasional shaking
and filter. Discard the first 10 mL of the filtrate, transfer
the subsequent 25 mL of the filtrate to a Nessler tube and
add ethanol to make 50 mL. Proceed as directed under
the Chloride Limit Test using this solution as the test solution. Prepare the control solution as follows: to 0.10
mL of 0.01 mol/L hydrochloric acid VS, add 6 mL of dilute nitric acid and water to make 25 mL, then ethanol to
make 50 mL.
(4) IodineDissolve 0.20 g of Amidotrizoic Acid in
2.0 mL of sodium hydroxide TS, add 2.5 mL of 0.5
mol/L sulfuric acid TS, allow to stand for 10 minutes
with occasional shaking, add 5 mL of chloroform, shake
well and allow to stand: the solution is colorless in the
chloroform layer.
(5) Heavy metalsProceed with 2.0 g of Amidotrizoic Acid according to Method 2 and perform the test.
Amidotrizoic Acid according to Method 3 and perform
the test (not more than 3.3 ppm).
hours).
Amikacin
OH
HO
NH2
HO
H2N
OH
O
HO
NH2
HO
OH
N
H
HO
NH2
C22H43N5O13: 585.60
Amikacin contains not less than 900 g (potency) of
amikacin (C22H43N5O13) per mg, calculated on the anhydrous basis.
Description Amikacin is a white to light grayish white
wool-like powder.
Identification Weigh about 60 mg each of Amikacin
and Amikacin Sulfate RS, dissolve each in water to make
the solutions so that each mL contains 6 mg, and use
these solutions as the test solution and the standard solution, respectively. Perform the test with these solutions as
directed under Thin-layer Chromatography. Spot 10 L
of the test solution and the standard solution on a plate of
silica gel for thin-layer chromatography. Develop the
plate with the developing solvent which is a mixture of
methanol, concentrated ammonia, and chloroform
(60:30:25) in a 230 x 230 x 90 mm developing chamber
for 5 hours and 30 minutes, in which 200 x 30 mm
Whatman filter paper or an identical filter paper strip is
hung in the front of the chamber, the plate is slanted for
the silica gel layer to face toward the front side of the
chamber, and the cover with holes is placed on the top.
The holes are sealed with scotch tape except the holes
above the filter paper. Air-dry the plate, and spray evenly
the mixture of 100 mL of 1 % ninhydrinbutanol solution
and 1 mL of pyridine, and heat at 110 C for 10 minutes:
the spots obtained from the test solution and the standard
solution is the same in the Rf value.
Assay Transfer about 0.5 g of Amidotrizoic Acid, accurately weighed, to a saponification flask, dissolve in 40
mL of sodium hydroxide TS, add 1 g of zinc powder,
connect to a reflux condenser, boil for 30 minutes, cool
and filter. Wash the flask and the filter paper with 50 mL
of water and combine the washings and the filtrate. Add
5 mL of glacial acetic acid to this solution and titrate
with 0.1 mol/L silver nitrate VS until the color of the
precipitate changes from yellow to green (indicator: 1
mL of tetrabromophenolphthalein ethyl ester TS).
Specific Optical Rotation [ ]D : +97 ~ +105(0.5 g

calculated on the anhydrous basis, water, 25 mL, 100
mm).

= 20.464 mg of C11H9I3N2O4
pH The pH of a solution obtained by dissolving 0.1 g

of Amikacin in 10 mL of water is between 9.5 and 11.5.

tight containers.
Crystalliity Test It meets the requirement.

25
Water Not more than 8.5 % (0.1 g, volumetric titration,

direct titration).
Residue on Ignition Not more than 1.0 % (1 g).
Assay The Cylinder-plate method (1) Agar media
KP 9 53
for seed and base layer- Use the medium in I 2 1) (1)
2 under Microbial Assay for Antibiotics.
(2) Test organism- Bacillus subtilis ATCC 6633.

(3) Weigh accurately about 15 mg (potency) of Amikacin, and dissolve in sterile distilled water to make the
solution so that each mL contains 400 g (potency), and
use the solution as the test stock solution. Take exactly a
suitable amount of the test stock solution, add 0.1 mol/L
phosphate buffer solution, pH 8.0 to make solutions so
that each mL contains 20.0 g (potency) and 5.0 g (potency), and use these solutions as the high concentration
test solution and the low concentration test solution, respectively. Separately, weigh accurately about 15 mg
(potency) of Amikacin Sulfate RS, dissolve in 0.05
mol/L phosphate buffer solution, pH 6.0 to make the solution so that each mL contains 400 g (potency), and
use the solution as the standard stock solution. Keep the
standard stock solution between 5 C and 15 C, and use
within 30 days. Take exactly a suitable amount of the
standard stock solution in use, add 0.1 mol/L phosphate
buffer solution, pH 8.0 to make solutions so that each mL
contains 20.0 g (potency) and 5.0 g (potency), and use
these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these solutions according to
the Cylinder-plate method (I 8) as directed under Microbial Assay for Antibiotics.
Amikacin Sulfate
OH
HO
NH2
HO
H2N
OH
HO
OH
NH
O
NH2
Specific Optical Rotation

water, 25 mL, 100 mm).
[ ]20
D : +69 ~ +79 (0.25 g,

of Amikacin Sulfate in 10 mL of water is between 6.0
and 7.5.
Purity Heavy metals Proceed with 1.0 g of Amikacin Sulfate according to Method 2 and perform the test.
xH2SO4
O
HO
purple color develops.

(2) To 20 mg of Amikacin Sulfate add 2 mL of 0.06
mol/L phosphate buffer solution, pH 5.6, and add 1 mL
of ninhydrin TS and boil: the blue-purple color develops.
(3) To 10 mg of Amikacin Sulfate add 1 mL of water,
add 1 mL of 1 mol/L of sodium hydroxide TS, and mix
the solution and add 2 mL of cobalt nitrate TS: the purple
color develops.
(4) To 20 mg of Amikacin Sulfate add 2 mL of water,
and add 1 mL of barium chloride TS: the solution turns
to turbid.
(5) Weigh about 50 mg each of Amikacin Sulfate and
Amikacin Sulfate RS, dissolve each in water to make the
solutions so that each mL contains 10 mg, and use these
solutions as the test solution and the standard solution,
respectively. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot 10 L of
the test solution and the standard solution on a plate of
plate with the mixture of methanol, concentrated ammonia, water, and chloroform (4:2:1:1), and air-dry the plate.
Spray evenly 0.2 % ninhydrin unsaturated butanol solution: the spots obtained from the test solution and the
standard solution is the same in the Rf value.
OH
H
H2N
C22H43N5O13xH2SO4
Amikacin Sulfate is the sulfate of a derivative of kanamycin.
Amikacin Sulfate contains not less than 635 g (potency)
of amikacin (C22H43N5O13: 585.60) per mg, calculated on
the dried basis.
Description Amikacin Sulfate is a white to yellowish
white powder, and is almost odorless and tasteless.
Amikacin Sulfate is very soluble in water, and practically
insoluble in ethanol or in ether.
Identification (1) To 50 mg of Amikacin Sulfate add 3
mL of water, and add 4 mL of anthrone TS: the blue-
Sterility Test It meets the requirement, when Amikacin

Sulfate is used in a sterile preparation.
Bacterial Endotoxins Less than 0.50 EU per mg of
amikacin, when Amikacin Sulfate is used in a sterile
preparation.
Loss on Drying Not more than 5.0 % (0.1 g, in vacuum, 60 C, 3 hours).
1
for seed and base layer- Use the medium in I 2 1) (1)
under Microbial Assay for Antibiotics.
(2) Test organism- Bacillus subtilis ATCC 6633.
(3) Weigh accurately about 15 mg (potency) of Amikacin Sulfate, and dissolve in sterile distilled water to
make the solution so that each mL contains 400 g (potency), pipet exactly a suitable amount of this solution,
add 0.1 mol/L phosphate buffer solution, pH 8.0 to make
solutions so that each mL contains 20.0 g (potency) and
5.0 g (potency), and use these solutions as the high
concentration test solution and low concentration test solution, respectively. Separately, weigh accurately about
15 mg (potency) of Amikacin Sulfate RS, dissolve in
0.05 mol/L phosphate buffer solution, pH 6.0 to make the
solution so that each mL contains 400 g (potency), and
use the solution as the standard stock solution. Keep the
standard stock solution between 5 C and 15 C, and use
standard stock solution in use, add 0.1 mol/L phosphate
Aminocaproic Acid
H 2NCH 2CH 2CH 2CH 2CH 2CO 2H
C6H13NO2: 131.17
Aminocaproic Acid contains not less than 98.5% and not
more than 101.5% of aminocaproic acid (C6H13NO2),
calculated on the anhydrous basis.
Description Aminocaproic Acid is a fine white crystalline powder and is odorless. It is freely soluble in water,
acid, or alkali, slightly soluble in methanol or in ethanol,
and practically insoluble in chloroform or in ether.
A solution of Aminocaproic Acid is neutral.
Melting pointAbout 205 C.
Identification Determine the infrared spectra of Aminocaproic Acid and Aminocaproic Acid RS as directed in
Spectrophotometry, respectively: both spectra exhibit
similar intensities of absorption at the same wavenumbers.
Purity Heavy metalsProceed with 1.0 g of Aminocaproic Acid according to Method 2 and perform the test.
Water Not more than 0.5% (1 g, volumetric titration,
direct titration).
Assay Weigh accurately about 0.12 g of Aminocaproic
Acid and add water to make exactly 10 mL. Pipet exactly
5 mL of this solution, add exactly 2 mL of the internal
standard solution and dilute with water to make 100 mL
and use this solution as the test solution. Separately,

weigh accurately about 0.12 g of Aminocaproic Acid RS,
o
previously dried 105 C for 30 minutes, dissolve in water to make exactly 10 mL, then pipet exactly 5 mL of
this solution, add exactly 2 mL of internal standard solution and dilute with water to make 100 mL and use this
to the following conditions and calculate the ratios, QT
and QS , of the peak area of Aminocaproic Acid to that
of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of Aminocaproic Acid (C6H13NO2)
= amount (mg) of Aminocaproic Acid RS
QT
QS
Internal standard solutionDissolve 25 mg of methionine in 20 mL of water.

about 30 C.
Mobile phase: Dissolve 0.55 g of sodium 1heptanesulphonate to make 1000 mL and use this solution as solution A. Dissolve 10 g of monobasic potassium
phosphate in 300 mL of solution A, add 250 mL of methanol, then add 300 mL of solution A and mix. Adjust
pH to 2.2 with phosphoric acid, and add solution A to
make 1000 mL.
System suitability
with 20 L of the standard solution under the above operating conditions, Aminocaproic acid and methionine
are eluted in this order with the resolution between their
above operating conditions, the relative standard deviation of the ratio of the peak area is not more than 2.0%.
KP 9 55
Aminocaproic Acid Tablets

Aminocaproic Acid Tablets contain not less than 95.0%
and not more than 105.0% of the labeled amount of aminocaproic acid (C6H13NO2: 131.17).
Method of Preparation Prepare as directed under Tablets, with Aminocaproic Acid.
Identification Powder two Aminocaproic Acid Tablets,
add 10 mL of water, shake well, with 100 mL of acetone
and filter. Mix the filtrates with shaking and allow to
stand for 15 minutes to be crystallized. Filter the crystals
through a glass filter (G4) and wash with 25 mL of acetone and dry at 105 C for 30 minutes and cool. With the
residue, proceed as directed in the Identification under
Aminocaproic Acid.
Dissolution Test Perform the test with 1 tablet of Aminocaproic Acid Tablets at 100 revolutions per minute according to Method 1 under the Dissolution Test, using
900 mL of water as dissolution solution. Take the dissolved solution after 45 minutes from the start of the test
weigh accurately sufficient quantity of Aminocaproic Aco
id RS, previously dried at 105 C for 30 minutes, dissolve in water, so that each mL contains about 500 g of
aminocaproic acid and use this solution as the standard
solution. To 1 mL each of the test solution and the standard solution add 20.0 mL of borate buffer solution, pH
9.5, and 3.0 mL of sodium -naphthoquinone-4-sulfonate
TS, prepared before using, (1 in 500), shake, and allow
to stand in a water-bath at 65 5 C for 45 minutes. After cooling, add water to make exactly 50 mL and mix.
Determine the absorbances of these solutions at 460 nm
as directed under Ultraviolet-visible Spectrophotometry,
using the blank solution as the blank. The dissolution
rate of Aminocaproic Acid Tablets in 45 minutes is not
less than 75%.
Borate buffer solution, pH 9.5Dissolve 6.185 g of
boric acid and 7.930 g of potassium chloride in water,
add 60 mL of 0.1 mol/L of sodium hydroxide VS and add
water to make 2 L. Add 0.1 mol/L Sodium hydroxide, if
necessary, to adjust to a pH of 9.5 0.1.
Aminocaproic Acid Tablets. Weigh accurately a portion
of the powder, equivalent to about 0.5 g of aminocaproic
acid (C6H13NO2), add 100 mL of glacial acetic acid, dissolve by heating, cool and titrate with 0.1 mol/L perchloric acid in dioxane VS until a blue color develops
[indicator: 10 drops of chlorobenzene TS (1 in 500) of
methylrozaniline chloride]. Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid in dioxane VS
= 13.12 mg of C6H13NO2
Aminophylline Hydrate
O
H
N
H3C
N
H2NCH2CH2NH2
O
N
CH3
X H 2O
N
2
C14H16N8O4 C2H8N2xH2O
Aminophylline Hydrate contains not less than 84.0% and
not more than 86.0% of theophylline (C7H8N4O2:
180.16) and not less than 14.0% and not more than
15.0% of ethylenediamine (C2H8N2: 60.10), calculated
on the anhydrous basis.
Description Aminophylline Hydrate is a white to pale
yellow granule or powder, is odorless or has slightly
ammonia-like odor and has a bitter taste.
Aminophylline Hydrate is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol or
in ether.
To 1 g of Amimophylline Hydrate, add 5 mL of water
and shake: it dissolves almost completely. Separation of
crystals begins in 2 to 3 minutes and these crystals dissolve on the addition of a small amount of ethylenediamine
Aminophylline Hydrate is gradually colored by light and
gradually loses ethylenediamine in air.
Identification (1) Dissolve 0.75 g of Aminophylline
Hydrate in 30 mL of water and use this solution as the
test solution. When 1 mL of dilute hydrochloric acid is
added to 20 mL of the test solution, a precipitate is gradually formed. Filter the precipitate, recrystallize from
water and dry at 105 C for 1 hour: the crystals so obtained melt between 271 C and 275 C.
(2) Dissolve 0.1 g of the crystals obtained in (1) in 50
mL of water and to 2 mL of this solution, add tannic acid
TS drop-wise: a white precipitate is produced and this
precipitate dissolves upon drop-wise addition of tannic
acid TS.
(3) To 10 mg of the crystals obtained in (1), add 10
drops of hydrogen peroxide TS and 1 drop of hydrochloric acid and evaporate on a water-bath to dryness: the
residue shows a yellow-red color. Invert the dish containing the residue over a vessel containing 2 to 3 drops of
ammonia TS: the color of the residue changes to red-
purple, which is destroyed on the addition of 2 to 3 drops
of sodium hydroxide TS.
(4) Dissolve 10 mg of the crystals obtained in (1) in 5
mL of water, add 3 mL of ammonia-ammonium chloride
buffer solution, pH 8.0 and 1 mL of cupric sulfatepyridine TS and mix. Add 5 mL of chloroform to the
mixture and shake: the chloroform layer develops a
green color.
(5) To 5 mL of the test solution obtained in (1), add 2
drops of cupric sulfate TS: a purple color develops. Add
1 mL of cupric sulfate TS: the color changes to blue and
green precipitates are formed on staining.
pH Dissolve 1.0 g of Aminophylline Hydrate in 25 mL
of water: the pH of this solution is between 8.0 and 9.5.
Purify (1) Clarity and color of solution Dissolve
1.0 g of Aminophylline Hydrate in 10 mL of hot water:
the solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 1.0 g of Aminophylline Hydrate according to Method 2 and perform the
direct titration).
Assay (1) TheophyllineWeigh accurately about 0.25
g of Aminophylline Hydrate and dissolve in 50 mL of
water and 8 mL of ammonia TS by gentle warming on a
water-bath. Add exactly 20 mL of 0.1 mol/L silver nitrate
VS, warm on a water-bath for 15 minutes, allow to stand
between 5 C and 10 C for 20 minutes, collect the precipitate by suction and wash with three 10 mL portions of
water. Combine the filtrate and washings and add dilute
nitric acid to make neutral. Add 3 mL of dilute nitric acid
and titrate the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium
ferric sulfate). Perform a blank determination and make
= 18.016 mg of C7H8N4O2
(2) EthylenediamineWeigh accurately about 0.5 g
of Aminophylline Hydrate, dissolve in 30 mL of water
and titrate with 0.1 mol/L hydrochloric acid VS (indicator: 3 drops of bromphenol blue TS).
Each mL of 0.1 mol/L hydrochloric acid VS
= 3.0049 mg of C2H8N2
tight containers.
Aminophylline Injection
Aminophylline Injection is an aqueous solution for injection. Aminophylline Injection contains not less than
75.0% and not more than 86.0% of theophylline
more than 20.0% of ethylenediamine (C2H8N2: 60.10) of
the labeled amount of aminophylline. The concentration
of Aminophylline Injection is expressed as the quantity
of aminophylline hydrate (C16H24N10 O42H2O: 456.46).
Method of Preparation Prepare as directed under Injections, with Aminophylline hydrate. Aminophylline Injection may be prepared with Theophylline and its
equivalent Ethylenediamine, instead of Aminophylline
hydrate. Aminophylline Injection may contain not more
than 60 mg of ethylenediamine as a stabilizer for each g
of Aminophylline hydrate.
Description Aminophylline Injection is a clear and colorless liquid. Aminophylline Injection has a slightly bitter taste.
Aminophylline Injection gradually changes in color by
light.
pHBetween 8.0 and 10.0.
Identification To a volume of Aminophylline Injection,
equivalent to 0.75 g of Aminophylline hydrate according
to the labeled amount, add water to make 30 mL. Proceed with this solution as directed in the Identification
under Aminophylline hydrate.
It
Determination of Volume of Injection in Containers

It meets the requirement.
Assay (1) TheophyllineTo an accurately measured
volume of Aminophylline Injection, equivalent to about
0.2 g of theophylline (C7H8N4O2) (about 0.25 g of Aminophylline Hydrate), add 15 mL of water, 8 mL of ammonia TS and 20 mL of silver nitrate TS and warm in a
water-bath for 15 minutes. Cool to between 5 C and 10
C for 20 minutes, filter the precipitate through a glass
filter (G4) and wash with three 10 mL volumes of water.
Dissolve the precipitate in 5 mL of nitric acid and wash
the filter with three 10 mL volumes of water. Combine
the nitric acid solution and washings and titrate with 0.1
mol/L ammonium thiocyanate VS (indicator: 2 mL of
ammonium ferric sulfate TS).
KP 9 57
Each mL of 0.1 mol/L ammonium thiocyanate VS
= 18.016 mg of C7H8N4O2
(2) EthylenediamineTo an accurately measured
volume of Aminophylline Injection equivalent to about
30 mg of ethylenediamine (C2H8N2)(about 0.2 g of Aminophylline hydrate), add water to make 30 mL and titrate
with 0.1 mol/L hydrochloric acid VS (indicator: 2 to 3
drops of bromphenol blue TS)
= 3.0049 mg of C2H8N2
hermetic containers.
tion solution. Take the dissolved solution after 45 minutes from the start of the test, filter, make any necessary
dilution and use this solution as the test solution. Separately, weigh accurately about sufficient quantity of
Aminophylline RS, previously dried at 105 C for 4
hours, make the same concentration as the test solution
and use this solution as the standard solution. Determine
the absorbances of the test solution and the standard solution at 269 nm as directed under Ultraviolet-visible
Spectrophotometry. The dissolution rate of Aminophylline Tablets in 45 minutes is not less than 75%.
Aminophylline Tablets
Aminophylline Tablets contain not less than 75.0% and
not more than 86.0% of the labeled amount of theophylline (C7H8N4O2: 180.16) and not less than 12.0% and not
more than 14.0% of the labeled amount of ethylenediamine (C2H8N2: 60.10). The amount of Aminophylline
Tablets is expressed as the quantity of aminophylline hydrate (C16H24N10O42H2O: 456.46).
Method of Preparation Prepare as directed under Tablets, with Aminophylline Hydrate.
Identification (1) Weigh a portion of powdered Aminophylline Tablets, equivalent to 0.5 g of Aminophylline
Hydrate according to labeled amount, add 25 mL of water, shake well, then filter. This filtrate changes moistened red litmus paper to blue. Mix the filtrate with 1 mL
of 3 mol/L of hydrochloric acid, then obtain the crystals
of Theophylline. Cool, if necessary, and precipitate. Filter the precipitate (the filtrate is used for identification
(2)), wash with small volume of cold water and dry at
105 C for 1 hour. Proceed with this crystal as directed in
the Identification (3) under Aminophylline Hydrate. And
recrystalize this crystal with water, dry at 105 C for 1
hour, and the melting point of this crystal is not less than
270 C and not more than 274 C.
(2) To the filtrate from (1), add 0.5 mL of benzenesulfonyl chloride and 5 mL of 1 mol/L sodium hydroxide
TS to make alkaline, shake for 10 minutes, and then add
5 mL of 3 mol/L hydrochloric acid to make acidic, then
obtain the crystals of ethylenediamine disulfonamide,
wash, recrystalize, dry at for 105 C for 1 hour: the melting point of this crystals is not less than 164 C and not
more than 171 C.
Dissolution Test This test applies to naked tablets. Perform the test with 1 tablet of Aminophylline Tablets at 50
revolutions per minute according to Method 2 under the
Dissolution Test, using 900 mL of water, as the dissolu-
Assay (1) TheophyllineWeigh accurately and powder not less than 20 Aminophylline Tablets. Weigh accurately a portion of the powder, equivalent to about 2 g of
aminophylline hydrate (C16H24N10O42H2O), add 50 mL
of water and 15 mL of ammonia TS, warm at 50 C and
allow to stand for 30 minutes with occasional shaking.
Cool to the room temperature and add water to make exactly 200 mL. Pipet exactly 50 mL of this solution, centrifuge, pipet exact amount of the supernatant, equivalent
to 0.2 g of theophylline, into a conical flask and add water to make about 40 mL. Then add 8 mL of ammonia TS,
add 20 mL of 0.1 mol/L silver nitrate VS, warm in waterbath for 15 minutes, then cool at between 5 C and 10 C
for 20 minutes, filter the precipitate through a glass filter
(G4) and wash with three 10 mL volumes of water. Collect the filtrate and washings, add nitric acid to make
acidic, then add 3 mL of nitric acid. After cooling, titrate
the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium ferric sulfate TS).
= 18.016 mg of C7H8N4O2
(2) EthylenediamineWeigh accurately and powder
not less than 20 Aminophylline Tablets. Transfer a portion, weighed accurately, of the powder, equivalent to
about 0.35 g of aminophylline hydrate (C16H24N10O4
2H2O) into a conical flask, add 200 mL of water, digest
at 50 C with frequent shaking for 30 minutes. After
cooling, filter this solution to another conical flask, wash
with water until the last washing is neutral to litmus and
titrate with 0.1 mol/L hydrochloric acid VS (indicator: 2
to 3 drops of methyl orange TS).
= 3.0049 mg of C2H8N2
Amitriptyline Hydrochloride
HCl
(7 : 3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
CH3
CHCH2CH2N
CH3

tight containers.
C20H23NHCl: 313.86
Amitriptyline Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of amitriptyline hydrochloride C20H23NHCl).
Description Amitriptyline Hydrochloride is a colorless
crystal or a white to pale yellowish crystalline powder.
Amitriptyline Hydrochloride has a bitter taste and a
numbing effect.
Amitriptyline Hydrochloride is freely soluble in water, in
ethanol or in glacial acetic acid, soluble in acetic anhydride, and practically insoluble in ether.
pHDissolve 1.0 g of Amitriptyline Hydrochloride
in 20 mL of water: the pH of this solution is between 4.0
and 5.0.
Identification (1) Dissolve 5 mg of Amitriptyline Hydrochloride in 3 mL of sulfuric acid: a red color is observed. Add 5 drops of potassium bichromate TS to this
solution: it turns dark brown.
(2) Acidify 1 mL of a solution of Amitriptyline Hydrochloride (1 in 500) with 0.5 mL of dilute nitric acid
and add 1 drop of silver nitrate TS: a white precipitate is
produced.
(3) Determine absorption spectra of solutions of Amitriptyline Hydrochloride and amitriptyline hydrochloride
RS, in water (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
Melting Point

g of Amitriptyline Hydrochloride in 20 mL of water: the
(2) Heavy metalsProceed with 2.0 g of Amitriptyline Hydrochloride according to Method 2 and perform
hours).
Assay Weigh accurately about 0.5 g of Amitriptyline
Hydrochloride, previously dried and dissolve in 50 mL
of a mixture of acetic anhydride and glacial acetic acid
Injection
Amitriptyline Hydrochloride Injection is a sterile solution of Amitriptyline Hydrochloride in water for injection.
Amitriptyline Hydrochloride Injection contains not less
amount of amitriptyline hydrochloride (C20H23NHCl:
313.86).
Method of Preparation Prepare as directed under Injections, with Amitriptyline Hydrochloride.
Identification (1) Pipet 1 mL of Amitriptyline Hydrochloride Injection into a separator containing 10 mL
of water and 1 mL of 1 mol/L sodium hydroxide TS, mix
and extract with two 10 mL volumes of dichloromethane.
Evaporate the extracts on a steam-bath just to dryness.
Dissolve the residue in methanol, add 1 mL of 1.2 mol/L
hydrochloric acid, then add methanol to make 100 mL.
Dilute 10 mL of this solution with methanol to make 100
mL and use this solution as the test solution. Separately,
prepare the standard solution with Amitriptyline Hydrochloride RS as directed for the preparation of the test
solution. Determine the absorption spectra of the test solution and the standard solution, respectively, as directed
under Ultraviolet-visible Spectrophotometry: both spectra exhibit maximum at the same wavelength.
(2) The retention time of the major peak in the chromatogram of the test preparation corresponds to that in
the chromatogram of the standard preparation, as obtained in the Assay.
Pyrogen Test Amitriptyline Hydrochloride Injection,
diluted with Isotonic Sodium Chloride Injection to a
concentration of 2.5 mg of Amitriptyline Hydrochloride
per mL according to the labeled amount, meets the requirement, the test dose being 1 mL per kg of rabbit.
KP 9 59

It

Assay Take accurately equivalent to about 50 mg of
Amitriptyline Hydrochloride, add water to make 250 mL
and use this solution as the test solution. Separately, dissolve an accurately weighed portion of Amitriptyline
Hydrochloride RS in water, previously dried at 60 C,
0.67 kPa and dilute quantitatively with water to obtain a
solution having a known concentration of about 0.2 mg
per mL and use this solution as the standard solution.
Perform the test with 20 L each of the test solution and
the standard solution as directed under the Liquid Chromatography according to the following conditions and
calculate the peak area of amitriptyline, AT and AS ,
Amount (mg/mL) of Amitriptyline Hydrochloride
(C20H23NHCl) = 250 C AT
V
AS
C: Concentration of the standard solution (mg/mL),

V: Volume of Amitriptyline Hydrochloride Injection
taken (mL).
to 10 m in particle diameter).
Temperature: A room temperature.
Mobile phase: Dissolve 11.04 g of monobasic sodium
phosphate in 900 mL of water, adjust with phosphoric acid to a pH of 2.5 0.5, dilute with water to make 1000
mL and prepare a mixture of this solution and acetonitrile (58 : 42).
System suitability
with 20 L of the standard solution under the above operating conditions, the symmetry factor is not more than
2.0.
above operating conditions, the relative standard deviation of the peak area is not more than 2.0.
Preserve in light-resistant
Tablets
Amitriptyline Hydrochloride Tablets contain not less
amount of amitriptyline hydrochloride (C20H23NHCl:
313.86).
Method of Preparation Prepare as directed under Tablets, with Amitriptyline Hydrochloride.
Identification (1) Weigh a portion of powdered Amitriptyline Hydrochloride Tablets, equivalent to 0.1 g of
Amitriptyline Hydrochloride according to the labeled
amount. Add 10 mL of chloroform, shake thoroughly and
filter. Evaporate the filtrate on a water-bath to about 2
mL, add ether until turbidity is produced and allow to
stand. Filter the crystals through a glass filter (G4) and
proceed as directed under the Identification (1) and (2)
under Amitriptyline Hydrochloride.
(2) Determine the absorption spectrum of a solution
of the crystals obtained in (1) (1 in 100000) as directed
under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 238 nm and 240 nm and a minimum between 228 nm and 230 nm.
Dissolution Test Perform the test with 1 tablet of Amitriptyline Hydrochloride Tablets at 50 revolutions per
minute according to Method 2 under the Dissolution Test,
using 900 mL of diluted phosphate buffer solution, pH
6.8 (1 in 2) as a dissolution solution. Take 20 mL or more
of the dissolved solution 60 minutes after starting the test
and filter through a membrane filter with pore size of not
more than 0.8 m. Discard the first 10 mL of the filtrate,
pipet the subsequent V mL of the filtrate, add diluted
phosphate buffer solution, pH 6.8 (1 in 2), to make exactly V mL, so that each mL contains about 11 g of amitriptyline hydrochloride (C20H23N.HCl) according to the
labeled amount and use this solution as the test solution.
Separately, weigh accurately about 55 mg of Amitriptyline Hydrochloride RS, previously dried at 105 C for 2
hours and dissolve in diluted phosphate buffer solution,
pH 6.8 (1 in 2) to make exactly 250 mL. Pipet exactly 5
mL of this solution, add diluted phosphate buffer solution,
pH 6.8 (1 in 2) to make exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 239 nm as directed under
the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Amitriptyline Hydrochloride Tablets in 60 minutes is not less than 70%.
Dissolution rate (%) with respect to the labeled amount
of amitriptyline hydrochloride (C20H23NHCl)
=
WS
AT V ' 1
18
AS V C
WS : Amount of Amitriptyline Hydrochloride RS (mg)
Amlodipine Besylate
C: Labeled amount of amitriptyline hydrochloride

(C20H23NHCl) in 1 tablet (mg).
H
N
H3C

Amitriptyline Hydrochloride Tablets. Weigh accurately a
portion of the powder, equivalent to about 50 mg of amitriptyline hydrochloride (C20H23NHCl) and add mobile
phase to make exactly 250 and filter. Discard the first 20
mL volume of the filtrate, and use next filtrate as the test
solution. Separately, weigh accurately about 50 mg of
Amitriptyline Hydrochloride RS, previously dried at 60
C, 0.67 kPa until the constant mass is attained and dissolve in mobile phase to make exactly 250 mL and use
this solution as the standard solution. Perform the test
with 20 L each of the test solution an the standard solution as diretected under the Liquid Chromatography according to the following conditions and calculate peak
areas of amitriptyline, AT and AS , from the test solution and the standard solution, respectively,.
Amount (mg) of amitriptyline hydrochloride
(C20H23NHCl)
= amount (mg) of Amitriptyline Hydrochloride RS
AT
AS
Column: A stainless steel column 4 mm in inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (between 5
and 10 m in particle diameter).
about 25 C.
Mobile phase: A mixture of Liquid A and acetonitrile
(58 : 42)
Liquid A: Dissolve 11.04 g of sodium dihydrogen
phosphate in 900 mL of water, adjust to pH 2.5 0.5
with phosphoric acid, and add water to make 1000 mL.
Flow rate: 2 mL/minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, the symmetry factor of the peak of
amitriptyline is not more than 2.0.
above operating conditions, the relative standard deviation of the peak area of amitriptyline is not more than
2.0%.
NH2
H3C
O
CH3
SO3H
O
Cl
and enantiomer
C20H25N2O5ClC6H6O3S : 567.05
Amlodipine Besylate contains not less than 97.0% and
not more than 102.0% of amlodipine besylate
(C20H25N2O5ClC6H6O3S), calculated on the anhydrous
basis.
Description Amlodipine Besylate is a white powder.
Amlodipine Besylate is freely soluble in methanol, sparingly soluble in ethanol, and slightly soluble in water or
2-propanol.
Identification (1) Dissolve 5.0 mg each of Amlodipine
Besylate and Amlodipine Besylate RS, respectively, in 1
vol% solution of 0.1 mol/L hydrochloric acid TS in methanol to make 100 mL. Determine the absorption spectra of the solutions respectively, as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Determine the infrared spectra of Amlodipine Besylate and Amlodipine Besylate RS, previously dried, as
directed in the paste method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) The principal spot in the chromatogram obtained
with the test solution (2) of i) Related substances is the
same in color and Rf value as the principal spot with the
standard solution (2.
+0.10 (0.25 g, methanol, 25 mL, 100 mm)
Purity Related substances) Dissolve 0.140 g of
the Amlodipine Besylate in methanol to make exactly 2
mL and use this solution as the test solution (1). To 1.0
mL of this solution add methanol to make exactly 10
mL and use this solution as the test solution (2). Separately, dissolve 70.0 mg of Amlodipine Besylate RS in
1.0 mL of methanol and use this solution as the standard
solution (1). To 1.0 mL of the standard solution (1) add
methanol to make 10 mL and use this solution as the
standard solution (2). To 3.0 mL of the standard solution
(2) add methanol to make 100 mL and use this solution
as the standard solution (3). To 1.0 mL of the standard
KP 9 61
solution (2) add methanol to make 100 mL and use this
solution as the standard solution (4). Perform the test
with these solutions as directed under the Thin-layer
Chromatography. Spot 10 L each of the test solutions
and the standard solutions on a plate of silica gel with
fluorescent indicator for thin-layer chromatography. Develop the plate with upper layer of a mixture of methyl
isobutyl ketone, water and glacial acetic acid (50 : 25 :
25) to a distance of about 15 cm and dry the plate at
80 C for 15 minutes. Examine under ultraviolet light
(main wavelength: 254 nm and 366 nm): any spot, other
than the principal spot, in the chromatogram obtained
with the test solution (1) is not more intense than that
with the standard solution (3) (not more than 0.3%) and
more intense spot than the one in the chromatogram from
the standard solution (4) is not more than 2 spots (not
more than 0.1%). This test is not valid unless the chromatogram from the standard solution (1) shows 2 clearly
separated minor spots with Rf values of about 0.18 and
0.22.
) Dissolve 50.0 mg of Amlodipine Besylate in mobile phase to make exactly 50 mL and use this solution as
the test solution (1). To 5.0 mL of the test solution (1)
add mobile phase to make exactly 100 mL and use this
solution as the test solution (2). Separately, dissolve 50.0
mg of Amlodipine Besylate RS in mobile phase to make
exactly 50 mL, pipet 5.0 mL of this solution, add mobile
the standard solution (1). To 3.0 mL of the test solution
(1) add mobile phase to make exactly 100 mL, pipet 5.0
mL of this solution, add mobile phase to make exactly 50
mL and use this solution as the standard solution (2).
Dissolve 5 mg of Amlodipine Besylate in 5 mL of strong
hydrogen peroxide, heat at 70 C for 45 minutes and use
this solution as the standard solution (3). Perform the test
with exactly 10 L each of the test (1) and the standard
solutions (2) and (3) as directed under Liquid Chromatography according to the following conditions: Amlodipine besylate related substance I {3-Ethyl-5-methyl-2[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl
pyridine-3,5-dicarboxylate} obtained with the test solution is not more than the area of the principal peak in the
chromatogram from the standard solution (2) (0.3%). Total area of all the other related substances is not more
than the area of the principal peak in the chromatogram
from the standard solution (2) (0.3%). Disregard any
peak due to benzene sulfonate (relative retention : about
0.2) and 0.1 times the area of the principal peak with the
Mobile phase: Mix 15 volumes of acetonitrile, 35 volumes of methanol and 50 volumes of a solution prepared
as follows: dissolve 7.0 mL of triethylamine in 1000 mL

of water and adjust to pH 3.0 0.1 with phosphoric acid.
Time span of measurement: About 3 times as long as
the retention time of amlodipine beginning after the solvent peak.
System suitability
operating conditions, minimum resolution is not less than
4.5 between the peaks corresponding to amlodipine and
related substance I; relative retention time of related substance I with reference to amlodipine (retention time =
about 7 minutes) is about 0.5. For the calculation of content, multiply the peak area of the related substance I by
2.
direct titration)
Assay Perform the test with the test solution (2) and
the standard solution (1) of Related substances ) as directed above conditions in Related substances ) and
calculate the percentage content of amlodipine besylate
from the areas of the peaks, AT and AS , respectively.
Amounts(mg) of amlodipine besylate
(C20H25N2O5ClC6H6O3S)
= amounts (mg) of Amlodipine Besylate RS
tight containers
AT
AS
Ammonia Water
Ammonia Water contains not less than 9.5 w/v% and not
more than 10.5 w/v% of ammonia (NH3: 17.03)
Description Ammonia Water is a clear, colorless liquid
and has a very pungent, characteristic odor.
Ammonia Water is alkaline.
20
: Between 0.95 and 0.96.
Specific Gravity d 20
Identification (1) Hold a glass rod moistened with hydrochloric acid near the surface of Ammonia Water:
dense white fumes are produced.
(2) Hold moistened red litmus paper near the surface
of Ammonia Water: it turns blue.
Purity (1) Residue on evaporationEvaporate 10.0
mL of Ammonia Water to dryness and dry the residue at
o
105 C for 1 hour: the weight of the residue is not more
than 2.0 mg.
(2) Heavy metalsEvaporate 5.0 mL of Ammonia
Water to dryness on a water-bath, add 1 mL of dilute hydrochloric acid to the residue and evaporate to dryness.
Dissolve the residue in 2 mL of dilute acetic acid, add
water to make 50 mL and perform the test using this solution as the test solution. Prepare the control solution
with 2.5 mL of standard lead solution, 2 mL of dilute
acetic acid and water to make 50 mL (not more than 5
ppm).
(3) Potassium permanganate-reducing substances
To 10.0 mL of Ammonia Water, add 40 mL of dilute
sulfuric acid while cooling and add 0.10 mL of 0.02
mol/L potassium permanganate VS: the red color of the
potassium permanganate does not disappear within 10
minutes.
Assay Measure exactly 5 mL of Ammonia Water, add
25 mL of water and titrate with 0.5 mol/L sulfuric acid
VS (indicator: 2 drops of methyl red TS).
= 17.031 mg of NH3
and store at not exceeding 30 C.
Amobarbital
O
H
N
CH3CH2
NH
(CH 3)2CHCH 2CH2
O
C11H18N2O3: 226.27
Amobarbital, when dried, contains not less than 99.0%
and not more than 101.0% of amobarbital (C11H18N2O3).
Description Amobarbital is a white crystal or crystalline powder, is odorless and has a slightly bitter taste.
Amobarbital is freely soluble in ethanol, in acetone or in
ether, sparingly soluble in chloroform and practically insoluble in water.
Amobarbital dissolves in sodium hydroxide TS or sodium carbonate TS.
pHThe pH of a saturated solution of Amobarbital
is between 5.0 and 5.6.
Identification (1) Boil 0.2 g of Amobarbital with 10
mL of sodium hydroxide TS: the gas evolved changes
moistened red litmus paper to blue.
(2) Dissolve 50 mg of Amobarbital in 2 to 3 drops of
ammonia-ammonium chloride buffer solution, pH 10.7
and 5 mL of diluted pyridine (1 in 10). Add 5 mL of
chloroform and 0.3 mL of cupric sulfate TS to the solu-
tion: a red-purple precipitate is produced in the aqueous

layer. Shake the mixture: a red-purple color is produced
in the chloroform layer.
(3) To 0.4 g of Amobarbital, add 0.1 g of anhydrous
sodium carbonate and 4 mL of water, shake and add a solution of 0.3 g of p-nitrobenzyl chloride in 7 mL of ethanol. Heat the mixture in a water-bath for 30 minutes under a reflux condenser and allow to stand for 1 hour. Filter the crystals produced, wash with 7 mL of sodium hydroxide TS and a small portion of water, recrystalize
from ethanol and dry at 105 C for 30 minutes: the crystals so obtained melt between 168 C and 173 C or between 150 C and 154 C.
Melting Point
Purity (1) Clarity and color of solution Dissolve 0.5

g of Amobarbital in 5 mL of sodium hydroxide TS: the
(2) ChlorideDissolve 0.30 g of Amobarbital in 20
mL of acetone and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as
the test solution. Prepare the control solution as follows:
take 0.30 mL of 0.01 mol/L hydrochloric acid VS, 20 mL
of acetone and 6 mL of dilute nitric acid and add water to
make 50 mL (not more than 0.035%).
(3) SulfateDissolve 0.40 g of Amobarbital in 20
mL of acetone and add 1 mL of dilute hydrochloric acid
and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as
follows: take 0.40 mL of 0.005 mol/L sulfuric acid VS,
20 mL of acetone and 1 mL of dilute hydrochloric acid
and add water to make 50 mL (not more than 0.048%).
(4) Heavy metalsProceed with 1.0 g of Amobarbital according to Method 2 and perform the test. Prepare
the control solution with 2.0 mL of standard lead solution
(5) Readily carbonizable substancesPerform the
test with 0.5 g of Amobarbital. The solution has no more
color than Color Matching Fluid A.
hours).
Residue on Ignition
Not more than 0.1% (1 g).
Assay Weigh accurately about 0.5 g of Amobarbital,

previously dried, and dissolve in 5 mL of ethanol and 50
mL of chloroform. Titrate with 0.1 mol/L potassium hydroxide-ethanol VS until the color of the solution
changes from yellow through pale blue to purple (indicator: 1 mL of alizarin yellow GG-thymolphthalein TS).
correction.
Each mL of 0.1 mol/L potassium hydroxide-ethanol VS
= 22.627 mg of Cl1H18N2O3
KP 9 63
tainers.
Amobarbital Sodium
for Injection
O
H
N
ONa
CH3CH2
N
(CH3)2CHCH2CH2
O
C11H17N2NaO3: 248.25
Amobarbital Sodium for Injection is a preparation for injection which is dissolved before use. When dried, Amobarbital Sodium for Injection contains not less than
98.5% and not more than 101.0% of amobarbital sodium
(C11H17N2NaO3) and not less than 92.5% and not more
than 107.5% of the labeled amount of amobarbital sodium (C11H17N2NaO3).
Method of Preparation Prepare as directed under Injections with Amobarbital Sodium.
Description Amobarbital Sodium for Injection is a
white crystal or a crystalline powder, is odorless and has
a bitter taste.
Amobarbital Sodium for Injection is freely soluble in
water or in ethanol, and practically insoluble in ether or
in chloroform.
pH The pH of a solution of Amobarbital Sodium
for Injection (1 in 10) is between 10.0 and 11.0.
Identification (1) Dissolve 1.5 g of Amobarbital Sodium for Injection in 20 mL of water and add 10 mL of
dilute hydrochloric acid with stirring: a white precipitate
is produced. Collect the precipitate, wash with four
10mL volumes of water and dry at 105 C for 3 hours: it
melts between 157 C and 160 C. With this precipitate,
proceed as directed in the Identification under Amobarbital.
(2) Ignite 0.5 g of Amobarbital Sodium for Injection,
cool and dissolve the residue in 10 mL of water: the solution responds to the Qualitative Tests (1) for sodium salt.
g of Amobarbital Sodium for Injection in 10 mL of freshly boiled and cooled water: the solution is clear and colorless.
(2) ChlorideDissolve 1.0 g of Amobarbital Sodium
for Injection in 49 mL of water, add 1 mL of glacial acetic acid, shake and filter. Discard the first 10 mL of the
filtrate and to the subsequent 30 mL of the filtrate, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.30 mL of 0.01
mol/L hydrochloric acid VS, add 0.5 mL of glacial acetic
acid, 6 mL of dilute nitric acid and water to make 50 mL

(3) SulfateDissolve 2.0 g of Amobarbital Sodium
for Injection in 49 mL of water, add 1 mL of glacial acetic acid, shake and filter. Discard the first 10 mL of the
filtrate and to the subsequent 25 mL of the filtrate, add
2.5 mL of dilute hydrochloric acid and water to make 50
mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.40 mL
of 0.005 mol/L sulfuric acid VS, add 0.5 mL of glacial
acetic acid,1 mL of dilute hydrochloric acid and water to
(4) Heavy metalsDissolve 2.0 g of Amobarbital
Sodium for Injection in 45 mL of water, add 5 mL of dilute hydrochloric acid, shake vigorously and warm in a
water-bath for 2 minutes with occasional shaking. Cool,
add 30 mL of water, shake and filter. Discard the first 10
mL of the filtrate, add 1 drop of phenolphthalein TS to
the subsequent 40 mL of the filtrate, add ammonia TS
until a slight red color develops and add 2.5 mL of dilute
acetic acid and water to make 50 mL. Perform the test
using this solution as the test solution. Prepare the control solution as follows: to 2.5 mL of dilute hydrochloric
acid, add 1 drop of phenolphthalein, add ammonia TS
until a pale red color develops and add 2.5 mL of dilute
acetic acid, 2.0 mL of standard lead solution and water to
make 50 mL (not more than 20 ppm).
(5) Neutral or basic substancesDissolve about 1 g
of Amobarbital Sodium for Injection, accurately weighed,
in 10 mL of water and 5 mL of sodium hydroxide TS,
then add 40 mL of chloroform and shake well. Separate
the chloroform layer, wash with two 5mL volumes of
water and filter. Evaporate the filtrate on a water-bath to
dryness and dry the residue at 105 C for 1 hour: the
weight of the residue is not more than 0.30%.
test with 0.5 g of Amobarbital Sodium for Injection: the
solution has no more color than Color Matching Fluid A.
hours).
Insoluble Particulate Matter Test for Injection
It
Uniformity of Dosage Units It meets the requirement

of the Content Uniformity Test.
Assay Weigh accurately the contents of not less than
10 samples of Amobarbital Sodium for Injection. Weigh
accurately about 0.5 g of the contents, previously dried,
transfer to a separator, dissolve in 20 mL of water, add 5
mL of ethanol and 10 mL of dilute hydrochloric acid and
extract with 50 mL of chloroform, then with three 25 mL
volumes of chloroform. Combine the chloroform extracts,
wash with two 5 mL volumes of water and extract the
washings with two 10 mL volumes of chloroform. Filter
the combined chloroform extracts into a conical flask
and wash the filter paper with three 5 mL volumes of
chloroform. Combine the filtrate and the washings and
add 10 mL of ethanol. Titrate with 0.1 mol/L potassium
hydroxide-ethanol VS until the color of the solution
changes from yellow through pale blue to purple (indicator: 2 mL of alizarin yellow GG-thymolphthalein TS).
Perform a blank determination with a mixture of 160 mL
of chloroform and 30 mL of ethanol and make any necessary correction.
= 24.825 mg of C11H17N2NaO3
Amoxicillin Hydrate
HO
HO
CH3
N
H
NH2
CH3
S
H
3H2O
C16H19N3O5S3H2O: 419.45
Amoxicillin Hydrate contains not less than 900 g (potency) per mg of amoxicillin (C16H19N3O5S: 365.40),
Description Amoxicillin Hydrate is a white to yellowwhite, crystal or crystalline powder.
Amoxicillin Hydrate is slightly soluble in water or methanol, very slightly soluble in ethanol, and practically
insoluble in ether.
Identification (1) Spot 0.1 mL of 1 % ninhydrin solution on filter paper, and dry at 105 C for 5 minutes. To
this spot 0.1 mL of 0.2 % Amoxicillin Hydrate solution,
dry at 105 C for 5 minutes, and cool to a room temperature: the red-purple color develops.
(2) Weigh 20 mg of Amoxicillin Hydrate, dissolve in
10 mL of water, and add 1 mL of Fehlings TS: the redpurple color develops immediately.
(3) To 2 mL of the aqueous solution of Amoxicillin
Hydrate (1 in 5000) add 1 mL of a solution of mercuric
(II) sulfate in 2.5 mol/L sulfuric acid solution (3 in 20),
heat for 2 minutes in boiling water bath, and add 1 mL of
sodium nitrite solution (1 in 1000) and heat for 2 minutes: a red-brown color is developed.
(4) Determine the infrared spectra of Amoxicillin
Hydrate and Amoxicillin RS, as directed in the potassium
bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption
at the same wave numbers.
(5) Weigh about 0.2 g of Amoxicillin Hydrate and
Amoxicillin RS, dissolve each in 0.1 mol/L hydrochloric
acid TS to make exactly 50 mL, and use these solutions
as the test solution and the standard solution. Perform the
test with these solutions as directed under Thin-layer
Chromatography. Spot 10 L of the test solution and the
standard solution on a plate of silica gel for thin-layer
chromatography. Develop the plate with the developing
solvent which is a mixture of methanol, chloroform, water and pyridine (9:8:3:1), air-dry the plate, and spray
evenly a ninhydrin solution in methanol (3 in 1000): the
spots obtained from the test solution and the standard solution are the same in the Rf value.
pH The pH of a solution obtained by dissolving 20 mg
of Amoxicillin Hydrate in 10 mL of water is between
3.5 and 6.0.
Purity Related substancesWeigh accurately about 3
mg of Amoxicillin Hydrate, dissolve in 2 mL of the mobile phase A, and use this solution as the test solution.
Weigh accurately about 3 mg of Amoxicillin Hydrate RS,
dissolve in 5 mL of the mobile phase A, pipet exactly
200 L of this solution, and add the mobile phase A to
make 2 mL. Pipet 500 L of this solution, and add the
mobile phase A to make 2 mL, and use this solution as
the standard solution. Perform the test with exactly 50
L each of the test solution and the standard solution as
directed under Liquid Chromatography according to the
following conditions, and determine each peak area.
Each peak area other than amoxicillin from the test solution is not more than the peak area of amoxicillin from
the standard solution (not more than 1 %). Also, total
peak areas other than amoxicillin from the test solution
are not more than the peak area of amoxicillin from the
standard solution (not more than 3 %).
Detector: An ultraviolet absorption photometer (wavelength: 254 nm)
inside diameter and about 250 mm in length, packed with
(10 m in particle diameter)
Column temperature: A constant temperature of about
25 C.
Mobile phase: Control the gradient by mixing the
mobile phase A and B as directed in the following table.
Mobile phase A: To 990 mL of 0.05 mol/L potassium
dihydrogen phosphate buffer solution, pH 5.0, add 10 mL
of acetonitrile.
Mobile phase B: To 800 mL of 0.05 mol/L potassium
dihydrogen phosphate buffer solution, pH 5.0, add 200
mL of acetonitrile.
KP 9 65
Time (min)
0
8
33
48
49
64
Mobile phase A
(vol %)
92
92
0
0
92
92
Mobile phase B
(vol %)
8
8
100
100
8
8
Amphotericin B
Water Not less than 11.5 and not more than 14.5 %
(0.1 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.1 g (potency) each of
Amoxicillin Hydrate and Amoxicillin RS, dissolve each
in water, add 15.0 mL of the internal standard solution
and water to make exactly 100 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L each of the test
Liquid Chromatography according to the following operating conditions, and determine the ratios, QT and QS ,
of the peak area of amoxicillin to that of the internal
standard.
Amount [g (potency)] of amoxicillin (C16H19N3O5S)
= Amount [g (potency)] of Amoxicillin RS
QT
QS
O
OH
OH
O
HOOC
Flow rate: 1.0 mL per minute.

System suitability
times with 50 L of the standard solution under the operating conditions, the relative standard deviation of the
peak areas of amoxicillin is not more than 1.0 %.
OH
OH
HO
OH
OH
O
H3C
CH3
OH
H
CH3
O
CH3
OH
OH
NH2
C47H73NO17: 924.08
Amphotericin B is a polyene macrolide substance having
antifungal activity produced by the growth of Streptomyces nodosus.
Amphotericin B contains not less than 750 g (potency)
of amphotericin B (C47H73NO17) per mg, calculated on
the dried basis.
Description Amphotericin B is a yellow to orange
powder.
Amphotericin B is soluble in dimethylsulfoxide, and
practically insoluble in water, in ethanol, or in ether.
Identification Weigh about 25 mg of Amphotericin B,
dissolve in 5 mL of dimethylsulfoxide, and add ethanol
anhydrous to make 50 mL. Determine the absorption
spectrum of this solution as directed under Ultravioletvisible Spectrophotometry, it exhibits maxima between
360 nm and 364 nm, and between 379 nm and 383 nm,
and between 403 nm and 407 nm.
Internal standard solutionWeigh accurately 0.7 g

of sodium benzoate, dissolve in water to make exactly
1000 mL.
pH The pH of a suspension obtained by suspending 0.3

g of Amphotericin B in 10 mL of water is between 3.5
and 6.0.
Column: A stainless steel column, about 4 mm in inside diameter and about 300 mm in length, packed with
Mobile phase: To 750 mL of water add 6.3 g of ammonium formate, and adjust the pH to 6.0 with formic
acid or ammonia TS. To this solution add 30 mL of methanol and water to make exactly 1000 mL.
time of the internal standard is about 1.5 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, the internal standard and amoxicillin
are eluted in this order with the resolution between these
Purity Amphotericin AWeigh accurately about 50

mg of Amphotericin B, dissolve in 10 mL of dimethylsulfoxide, add purified methanol to make exactly 50 mL.
Pipet exactly 4 mL of this solution, add purified methanol to make exactly 50 mL, and use this solution as the
test solution. Separately, weigh accurately about 20 mg
of Nystatin RS, dissolve in 40 mL of dimethylsulfoxide,
add purified methanol to make exactly 200 mL. Pipet exactly 4 mL of this solution, add purified methanol to
make exactly 50 mL, and use this solution as the nystatin
standard solution. Weigh accurately about 50 mg of Amphotericin B RS, dissolve in 10 mL of dimethylsulfoxide,
add purified methanol to make exactly 50 mL. Pipet exactly 4 mL of this solution, add purified methanol to
make exactly 50 mL, and use this solution as the amphotericin B standard solution. Separately, pipet exactly 10
mL of dimethylsulfoxide, add purified methanol to make
exactly 50 mL. Pipet exactly 4 mL of this solution, add
purified methanol to make exactly 50 mL, and use this
solution as the blank test solution. Determine the absorbances of these solutions at 282 nm and at 304 nm of this
solution as directed under Ultraviolet-visible Spectrophotometry (Not more than 5.0 %, w/w).
Amount [%] of amphotericin A
=
[( B S 2 ) (b S 1 )] 625
amount (g) of Amphoteric in B [( B a)-(b A)]
1%
A: E1 cm (282 nm) of nystatin
1%
B: E1 cm (282 nm) of amphotericin B
1%
a: E1 cm (304 nm) of nystatin
%
E11cm
b:
(304 nm) of amphotericin B
S1: Absorbance at 282 nn of the test solution
S2: Absorbance at 304 nn of the test solution
amount of these solutions before use, add dimethylsulfoxide to make solutions so that each mL contains 200
g (potency) and 50 g (potency), dilute each solution in
solution so that each mL contains 10.0 g (potency) and
and 2.5 g (potency), use these solutions as the high
concentration test solution and low concentration test solution, and the high concentration standard solution and
the low concentration standard solution, respectively.
Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under Microbial Assay for Antibiotics.
tight containers ( Below 15 C)
Ampicillin Hydrate
Sterility Test It meets the requirement, when Amphotericin B is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Amphotericin B is used in a sterile preparation,. Weigh 50 mg of
Amphotericin B, dissolve in the mixture of 39.2 mg of
desoxycholic aicd and 1.6 mL of sodium hydroxide (1 in
200), adjust the pH between 7.2 and 8.0 with hydrochloric acid, add distilled water for injection to make the solution so that each mL contains 1.0 mg (potency), and use
the solution as the test solution. Use five rabbits in the
test. If a body temperature of each rabbit is not more than
1.11 C, compared to the control body temperature, it
meets the requirement. The amount of injection is 1.0 mL
of the test solution per kg of body weight of rabbit.
Assay The Cylinder-plate method (1) Agar medium
1 under Mifor seed layer- Use the medium I 2 1) (4)
crobial Assay for Antibiotics.
(2) Agar medium for transfer- Use the medium in I 2
1 under Microbial Assay for Antibiotics.
1) (3)
(3) Liquid medium for suspension- Use the medium
in I 2 3) (1) under Microbial Assay for Antibiotics.
(4) Test organism- Saccharomyces cerevisiae ATCC
9763.
(5) Cylinder-agar plate- Use Petri dish plates without
dispensing the agar medium for base layer but with only
dispensing 8.0 mL of the seeded agar medium.
(6) Weigh accurately about 20 mg (potency) each of
Amphotericin B and Amphotericin B RS, dissolve in dimethylsulfoxide to make the solution so that each mL
contains 1 mg (potency), and use these solutions as the
test stock solution and the standard stock solution. Keep
the test stock solution and standard stock solution below
5 C, and use within 24 hours. Take exactly a suitable
HO
O
N
CH3
N
H
H2N
CH3
S
H
3H2O
C16H19N3O4S3H2O: 403.45
Ampicillin Hydrate contains not less than 900 g (potency) per mg of ampicillin (C16H19N3O4S: 349.41), calculated on the anhydrous basis.
Description Ampicillin. Hydrate is a white to light yellow-white, crystal or crystalline powder.
Ampicillin Hydrate is sparingly soluble in water, slightly
soluble in methanol, very slightly soluble in ethanol, and
Identification (1) Spot 0.1 mL of 1 % ninhydrin solution on filter paper, and dry at 105 C for 5 minutes. To
this spot additionally 0.1 mL of 0.1 % Ampicillin Hydrate solution, dry at 105 C for 5 minutes, and cool: the
purple color develops.
(2) Weigh 10 mg of Ampicillin. Hydrate, suspend in
1 mL of water, and add 2 mL of Fehlings TS and 2 mL
of water: the red-purple color develops immediately.
(3) To 2 mL of the solution of Ampicillin. Hydrate
that each mL contains 1 mg, add 0.5 mL of phenol and 5
mL of sodium hypochlorite TS: an odor of benzaldehyde
evolves persistently and orage precipitates occurs within
3 to 5 minutes.
(4) Determine the infrared spectra of Ampicillin Hydrate and Ampicillin Hydrate RS, as directed in the potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
KP 9 67
of Ampicillin Hydrate in 10 mL of water is between 3.5
and 6.0.
low-white crystal or crystalline powder.

Ampicillin Hydrate is very soluble in water, freely
soluble in ethanol, and slightly soluble in ether
Sterility Test It meets the requirement, when Ampicillin Hydrate is used in a sterile preparation.
Identification (1) Perform the tests according to Identification (1), (2) and (3) in Ampicillin Hydrate.
(2) Determine the absorption spectrum of Ampicillin
Sodium as directed in potassium bromide disk method
under Infrared Spectrophotometry, it exhibits absorption
at the wave numbers about 3400 cm 1 , 1760 cm 1 ,
1660 cm 1 , 1600 cm 1 , 1510 cm 1 , 1450 cm 1 ,
1400 cm 1 , 1320 cm 1 , and 1200 cm 1 .
(3) Ampicillin Sodium responds to the Qualitative
Tests 1) for sodium salt.
Water Not less than 12.0 and not more than 15.0 %
Assay Weigh accurately about 50 mg (potency) each of
Ampicillin Hydrate and Ampicillin Hydrate RS, dissolve
each in 80 mL of water, and add water to make exactly
water to make exactly 100 mL, and use these solutions as
the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak area of ampicillin, AT
and AS .
Amount [g (potency)] of ampicillin (C16H19N3O4S)
= Amount [g (potency)] of Ampicillin Hydrate RS
AT
AS
Column: A stainless steel column, about 4 mm in inside diameter and about 150 ~ 300 mm in length, packed
with octadecylsilanized silica gel for liquid chromatography (5 ~ 10 m in particle diameter)
Mobile phase: Dissolve 1.13 g of potassium dihydrogen phosphate in water, add 250 mL of methanol, 1 mL
of acetic acid, and add water to make 1000 mL.
Ampicillin Sodium
NaO
H2N
Sterility Test It meets the requirement, when Ampicillin Sodium is used in a sterile preparation.
ampicillin, when Ampicillin Sodium is used in a sterile
preparation.
direct titration).
Assay Perform the test according to Assay in Ampicillin Hydrate. Corresponding to the potency specified in
the labeling, weigh accurately about 50 mg (potency) of
Ampicillin Sodium, dissolve in 80 mL of water, and add
water to make exactly 100 mL. Pipet exactly 5 mL of this
solution, add water to make exactly 100 mL, and use this
solution as the test solution.
Amyl Nitrite
H
N
CH3
CH3
N
H

of Ampicillin Sodium in 10 mL of water is between 8.0
and 10.0.
O
O
Specific Optical Rotation [ ] 20

D : +246 ~ +272 (1.0 g
mm).
C5H11NO2: 117.15
S
H
C16H18N3NaO4S: 371.39
Ampicillin Sodium contains not less than 845 g (potency) per mg of ampicillin (C16H19N3O4S: 349.41), calculated on the anhydrous basis.
Description Ampicillin Sodium is a white to light yel-
Amyl Nitrite is the nitrous acid ester of 3-methyl-1butanol and contains a small quantity of 2-methyl-1butanol and the nitrous acid esters of other homologies.
Amyl Nitrite contains not less than 90.0% and not more
than 101.0% of amyl nitrite (C5H11NO2).
Description Amyl Nitrite is a clear, pale yellowish liquid and has a characteristic, fruity odor.
Amyl Nitrite is miscible with ethanol or with ether.
Amyl Nitrite is practically insoluble in water.
Amyl Nitrite is affected by light and by heat.
Amyl Nitrite is volatile at room temperature and flammable even at a low temperature.
Boiling pointAbout 97 C.
Identification Determine the infrared spectra of Amyl
Nitrite and Amyl Nitrite RS as directed in the liquid film
same wavenumbers.
Specific Gravity
20
: Between 0.871 and 0.880.
d 20
Purity (1) AcidTo 5 mL of Amyl Nitrite, add a mixture of 1.0 mL of 1 mol/L sodium hydroxide VS, 10 mL
of water and 1 drop of phenolphthalein TS, shake and allow to stand for 1 minute: the light red color of the water
layer does not disappear.
(2) WaterAllow 2.0 mL of Amyl Nitrite to stand in
ice-water: no turbidity is produced.
(3) AldehydeTo 3 mL of a mixture of equal volumes of silver nitrate TS and aldehyde free-ethanol, add
ammonia TS dropwise until the precipitate first formed is
redissolved. Add 1.0 mL of Amyl Nitrite and warm beo
tween 60 C and 70 C for 1 minute: a brown to black

color is not produced.
(4) Residue on evaporationEvaporate 10.0 mL of
Amyl Nitrite in a water-bath in a draft, carefully protecting from flame and dry the residue at 105 C for 1 hour:
the weight of the residue is not more than 1.0 mg.
Anthralin
OH
Dithranol

= 35.144 mg of C5H11NO2
hermetic containers not exceeding 10 mL capacity. Store
in a cold place with avoidance of fire.
OH
C14H10O3: 226.23
Anthralin contains not less than 97.0% and not more than
102.0% of anthralin (C14H10O3), calculated on the dried
basis.
Description Anthralin is a yellow powder. Anthralin is
odorless and tasteless.
Anthralin is freely soluble in chloroform, acetone or benzene, sparingly soluble in ethanol, in ether or in glacial
acetic acid and practically insoluble in water.
Anthralin is dissolves in sodium hydroxide TS
solutions of Anthralin and Anthralin RS in chloroform (1
in 100000) as directed under the Ultraviolet-visible Spectrophotometry, respectively: both spectra exhibit similar
intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Anthralin and
Anthralin RS as directed in the potassium bromide disk
spectra exhibit the same intensities of absorption at the
same wavenumbers.
Melting Point
Assay Weigh accurately a volumetric flask containing

10 mL of ethanol, add about 0.5 g of Amyl Nitrite and
weigh accurately again. Add exactly 25 mL of 0.1 mol/L
silver nitrate VS, then add 15 mL of potassium chlorate
solution (1 in 20) and 10 mL of dilute nitric acid, stopper
the flask immediately and shake vigorously for 5 minutes.
Dilute with water to make exactly 100 mL, shake and filter through dry filter paper. Discard the first 20 mL of the
filtrate, measure exactly 50 mL of the subsequent filtrate
and titrate the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium
ferric sulfate TS). Perform a blank determination and
Between 178 C and 181 C (Method 1).
Purity (1) Acid or baseSuspend Anthralin in water

and filter: the filtrate is neutral using Litmus paper.
(2) ChlorideSuspend approximately 1.0 g of Anthralin in 15 mL of water and filter. Collect 5 mL of the filtrate, make acidic with nitric acid and add 2 to 3 drops of
silver nitrate TS: the turbidity of this solution is not more
than that of 5 mL of the filtrate.
(3) SulfateCollect 5 mL of filtrate from (2), add 3
drops of 3 mol/L hydrochloric acid and 5 drops of barium chloride TS: the turbidity of this solution is not
more than that of 5 mL of the filtrate.
Loss on Drying Not more than 0.5% (1 g, silica gel, 4
hours).
Assay Weigh accurately about 0.25 g of Anthralin, dissolve in dichloromethane to make exactly 100 mL, pipet
exactly 10 mL of this solution and add dichloromethane
to make exactly 100 mL. Pipet exactly 5 mL of this solution, add 5.0 mL of the internal standard solution and the
mobile phase to make exactly 25 mL and use this solution as the test solution. Separately weigh accurately a
portion of Anthralin RS, dissolve in dichloromethane to
KP 9 69
make 250 g/mL. Pipet exactly 5 mL of this solution,
add 5.0 mL of the internal standard solution and the mobile phase to make exactly 25 mL and use this solution as
the standard solution. Perform the test with 10 L of
each of the test solution and the standard solution as directed under the Liquid Chromatography according to
the following conditions and calculate the ratios, QT
and QS , of the peak area of Anthralin to that of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of Anthralin (C14H10O3) = C
QT
QS
C: Concentration of the standard solution (g/mL).

Internal standard solutionWeigh a sufficient
amount of o-nitroanilin, dissolve in a small volume of
dichloromethane and add n-hexane to make 500 g/mL.
inside diameter and 25 cm in length, packed with porous
silica gel for liquid chromatography (5 to 10 m in particle diameter).
Mobile phase: A mixture of n-hexane, dichloromethane and glacial acetic acid (82 : 12 : 6).
System suitability
System performance: Dissolve 10 mg of Anthralin
RS and 20 mg of danthrone in and dilute with dichloromethane to make 100 mL. To 5 mL of this solution add 5
mL of n-hexane and mobile phase to make 25 mL. When
the procedure is run with 10 L of this solution under the
above operating conditions, anthralin and danthrone are
eluted in this order with the resolution between these
above operating conditions, the relative standard deviation of the ratios of the peak area to that of the internal
standard.is not more than 2.0%.
tight containers.
(C14H10O3: 226.23) when labeled amount of Anthralin in

Anthralin Ointment is not less than 0.1%. Anthralin
Ointment contains not less than 90.0% and not more than
130.0% of the labeled amount of anthralin (C14H10O3:
226.23) when the labeled amount of Anthralin in Anthralin Ointment is not more than 0.1%.
Method of Preparation Prepare as directed under the
Ointments with Anthralin.
Identification Retention time of major peak of the test
solution from Assay is the same as that of the standard
solution.
Assay Weigh accurately about 5 g of Anthralin Ointment in 100 mL of beaker and disperse with 20 mL of
dichloromethane and 10 mL of glacial acetic acid. Filter
the content with dichloromethane using Whatman filter
paper No. 4 to 100 mL volumetric flask. Wash the precipitate with dichloromethane to make 100 mL. Weigh accurately about 0.5 mg of anthralin (C14H10O3), add 2.0
mL of the internal standard solution and the mobile
phase to make exactly 25 mL and use this solution as the
Anthralin RS and dissolve in dichloromethane to make
0.25 mg/mL. Pipet exactly 2 mL of this solution, add 2.0
mL of the internal standard solution and the mobile
standard solution. Perform the test with the test solution
and the standard solution as directed under Assay of
Anthralin.
Amount(mg) of Anthralin (C14H10O3)
= 200
C: Concentration of the standard solution (mg/mL).

V: Volume of the test solution collected (mL).
Dithranol Ointment
Anthralin Ointment contains not less than 90.0% and not
more than 115.0% of the labeled amount of anthralin

L-Arginine
Hydrochloride
H
HN
CNHCH2CH2CH2
Anthralin Ointment
C QT
V QS
H2N
L-Arginine
Hydrochloride
COOH
HCl
NH2
C6H14N4O2HCl: 210.66
L-Arginine
Hydrochloride, when dried, contains not less

than 98.5% and not more than 101.0% of L-arginine hydrochloride (C6H14N4O2 HCl).
Description
L-Arginine
Hydrochloride is a white crys-
tal or crystalline powder, is odorless and has a slight,
characteristic taste.
L-Arginine Hydrochloride is freely soluble in water or in
formic acid, very slightly soluble in ethanol, and practically insoluble in ether.
Identification (1) Determine the infrared spectra of LArginine Hydrochloride and L-Arginine Hydrochlorode
RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry:
(2) A solution of L-Arginine Hydrochloride (1 in 50)

hours).
Assay Weigh accurately about 0.1 g of L-Arginine Hydrochloride, previously dried, dissolve in 2 mL of formic
acid, add exactly 15 mL of 0.1 mol/L perchloric acid VS
and heat in a water-bath for 30 minutes. After cooling,
add 45 mL of glacial acetic acid and titrate the excess
perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
pH Dissolve 1.0 g of L-Arginine Hydrochloride in 10

6.2.
D : Between +21.5 and
+23.5 (after drying, 2 g, 6 mol/L hydrochloric acid TS,
25 mL, 100 mm).
g of L-Arginine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.6 g of LArginine Hydrochloride and prepare the control solution
with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more
than 0.028%).
(3) AmmoniumPerform the test with 0.25 g of LArginine Hydrochloride, using the distillation under reduced pressure. Prepare the control solution with 5.0 mL
of standard ammonium solution (not more than 0.02%).
(4) Heavy metalsProceed with 1.0 g of L-Arginine
L-Arginine Hydrochloride according to Method 1 and
(6) Related substancesDissolve 0.20 g of LArginine Hydrochloride in 10 mL of water and use this
solution as the test solution. Pipet exactly 1 mL of the
test solution and add water to make exactly 10 mL. Pipet
exactly 1 mL of this solution and add water to make exactly 25 mL and use this solution as the standard solution.
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dehydrated
ethanol, water, n-butanol and strong ammonia water (2 :
1 : 1 : 1) to a distance of about 10 cm and dry the plate at
100 C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate and heat at 80 C for
5 minutes: any spot other than the principal spot from the
test solution is not more intense than the spot from the
standard solution.

= 10.533 mg of C6H14N4O2HCl
Arginine Hydrochloride
Injection
L-Arginine
Hydrochloride Injection
Arginine Hydrochloride Injection is an aqueous solution

for injection. Arginine Hydrochloride Injection contains
not less than 9.5% and not more than 10.5% of arginine
hydrochloride (C6H14N4O2HCl: 210.66).
Method of Preparation
Arginine Hydrochloride
100 g
Water for injection
sufficient quantity
To make 1000 mL
Prepare as directed under Injections, with the above ingredients. No preservative is added.
Description Arginine Hydrochloride Injection is a
clear, colorless liquid.
Identification (1) To 5 mL of a solution of Arginine
Hydrochloride Injection (1 in 100), add 1 mL of ninhydrin TS and heat for 3 minutes: a blue-purple color is observed.
(2) To 5 mL of a solution of Arginine Hydrochloride
Injection (1 in 10), add 2 mL of sodium hydroxide TS
and 1 to 2 drops of a solution of -naphthol in ethanol (1
in 1000), allow to stand for 5 minutes and add 1 to 2
drops of sodium hypochlorite TS: a red-orange color is
observed.
pH
Between 5.0 and 6.0.
KP 9 71
Pyrogen It meets the requirement when the test is performed with Arginine Hydrochloride Injection stored in a
container in a volume exceeding 10 mL.
It

Assay Pipet exactly 20 mL of Arginine Hydrochloride
Injection, add 7.5 mol/L hydrochloric acid TS to make
exactly 100 mL and determine the optical rotation, D, as
directed under the Optical Rotation Determination at 20
1 C in a 100 mm cell.
Amount (mg) of arginine hydrochloride
(C6H14N4O2HCl) = D 4444
Arotinolol Hydrochloride
OH
N
(CH 3)3CNHCH 2CCH 2S
H
drochloride and Arotinolol Hydrochloride RS, previously

(3) The solution of Arotinolol Hydrochloride (1 in
200) responds to Qualitative Tests (2) for Chloride.
Purity (1) Heavy metalsProceed with 1.0 g of Arotinolol Hydrochloride according to Method 2 and perform
(2) Related substancesDissolve 50 mg of Arotinolol Hydrochloride in 10 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test
solution, add methanol to make exactly 100 mL. Pipet
solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with
a mixture of chloroform, methanol, acetone and strong
ammonia water (30 : 10 : 10 : 1) to a distance of about 12
cm and air-dry the plate. Examine under ultraviolet light
Loss on Drying Not more than 0.2 g (1 g, in vacuum,
105 C, 4 hours).
O
S
C
NH2
HCl
and enantiomer
C15H21N3O2S3HCl: 408.00
Arotinolol Hydrochloride, when dried, contains not less

than 99.0% and not more than 101.0% of arotinolol hydrochloride (C15H21N3O2S3HCl).
Description Arotinolol Hydrochloride is a white to
pale yellow crystalline powder.
Arotinolol Hydrochloride is freely soluble in dimethylsulfoxide, slightly soluble in methanol or in water, very
slightly soluble in dehydrated ethanol, and practically insoluble in ether.
A solution of Arotinolol Hydrochloride in methanol (1 in
125) shows no optical rotation.
Identification (1) Determine absorption spectra of solutions of Arotinolol Hydrochloride and arotinolol hydrochloride RS, in methanol (1 in 75000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavelengths.
(2) Determine the infrared spectra of Arotinolol Hy-
Assay Weigh accurately about 1.5 g of Arotinolol Hydrochloride, previously dried and dissolve in dimethylsulfoxide to make exactly 25 mL. Pipet exactly 5 mL of
this solution, add 100 mL of water and 5 mL of sodium
hydroxide TS and extract with three 50 mL volumes of
dichloromethane. Filter each dichloromethane extract
through a pledget of absorbent cotton with anhydrous
sodium sulfate on it. Evaporate combined filtrate to dryness in vacuum. Dissolve the residue in 70 mL of glacial
(potentiometric titration, Endpoint Detection Method in
Titrimetry). Perform a blank determination and make any
= 20.400 mg of C15H21N3O2S3HCl
tight containers.
Each mL of 0.05 mol/L iodine VS

= 8.806 mg of C6H8O6
Ascorbic Acid
H
HO

tight containers.
CH2OH
O
Ascorbic Acid Injection
H
OH
OH
C6H8O6: 176.12
Vitamin C
Ascorbic Acid, when dried, contains not less than 99.0%

and not more than 101.0% of ascorbic acid (C6H8O6).
Description Ascorbic Acid is a white crystal or a white
crystalline powder, is odorless and has an acid taste.
Ascorbic Acid is freely soluble in water, sparingly soluble in ethanol, and practically insoluble in ether.
o

Identification (1) To 5 mL each of solution of Ascorbic Acid (1 in 50), add 1 drop of potassium permanganate TS or 1 to 2 drops of 2,6-dichlorophenol-indophenol
sodium TS: the color of the solution is discharged immediately in each case .
(2) Dissolve 0.1 g of Ascorbic Acid in 100 mL of a
solution of metaphosphoric acid (1 in 50). To 5 mL of
this solution, add iodine TS until the color of the solution
becomes pale yellow. Then add 1 drop of a solution of
cupric sulfate (1 in 1000) and 1 drop of pyrrole and
o
warm the mixture at 50 C for 5 minutes: a blue color
develops.

+21.5(2.5 g, water, 25 mL, 100 mm).
pH Dissolve 1.0 g of Ascorbic Acid in 20 mL of water:
the pH of this solution is between 2.2 and 2.5.
of Ascorbic Acid in 20 mL of water: the solution is clear
and colorless.
(2) Heavy metalsPerform the test with 1.0 g of Ascorbic Acid according to Method 1. Prepare the control
than 20 ppm).
hours).
Assay Weigh accurately about 0.2 g of Ascorbic Acid,
previously dried, dissolve in 50 mL of a solution of meta-phosphoric acid (1 in 50) and titrate with 0.05 mol/L
iodine VS (indicator: 1 mL of starch TS).
Vitamin C Injection
Ascorbic Acid Injection is an aqueous solution for injection. Ascorbic Acid Injection contains not less than
95.0% and not more than 115.0% of the labeled amount
of ascorbic acid (C6H8O6: 176.12).
Method of Preparation Prepare as directed under Injections, with the sodium salt of ascorbic acid.
Description Ascorbic Acid Injection is a clear, colorless liquid.
Identification (1) Measure a volume of Ascorbic Acid
Injection, equivalent to 0.5 g of Ascorbic Acid according
to the labeled amount, and add water to make 25 mL.
Proceed with 5 mL each of the solution as directed in the
Identification (1) under Ascorbic Acid.
(2) Measure a volume of Ascorbic Acid Injection,
equivalent to 5 mg of Ascorbic Acid according to the labeled amount. Add a solution of metaphosphoric acid (1
in 50) to make 5 mL and proceed with this solution as directed in the Identification (2) under Ascorbic Acid.
(3) Ascorbic Acid Injection responds to the Qualitative Tests (1) for sodium salt.
pH

It

Assay Measure exactly a volume of Ascorbic Acid Injection, equivalent to about 0.1 g of ascorbic acid
(C6H8O6), previously diluted with metaphosphoric acidacetic acid TS, if necessary and add metaphosphoric acid-acetic acid TS to make exactly 200 mL. Pipet exactly
2 mL of this solution and proceed with this solution as
directed in the Assay under Ascorbic Acid Powder.
KP 9 73
Each mL of 2,6-dichlorophenol-indophenol sodium TS
for titration = A mg of C6H8O6
Packaging and Storage Preserve under nitrogen atmosphere, in hermetic containers.
Ascorbic Acid Powder

Vitamin C Powder
Ascorbic Acid Powder contains not less than 95.0% and
not more than 120.0% of the labeled amount of ascorbic
acid (C6H8O6: 176.12).
Powders, with Ascorbic Acid.
dichlorophenol-indophenol sodium TS for titration.

2,6-Dichlorophenol-indophenol sodium TS for titration. PreparationDissolve 42 mg of sodium bicarbonate in 50 mL of water, add 50 mg of 2,6dichlorophenol-indophenol sodium and water to make
200 mL and filter. Prepare before use.
StandardizationWeigh accurately about 50 mg of
Ascorbic Acid RS, previously dried in a desiccator (silica
gel) for 24 hours, and dissolve in metaphosphoric acidacetic acid TS to make exactly 100 mL. Pipet exactly 2
mL of this solution, shake with 8 mL of metaphosphoric
acid-acetic acid TS and 2 mL of hydrogen peroxide TS
and titrate with 2,6-dichlorophenol-indophenol sodium
until a light red color persists for 5 seconds. Perform a
blank determination and make any necessary correction.
Calculate the quantity (A mg) of ascorbic acid (C6H8O6)
equivalent to 1 mL of this test solution.
Identification (1) Weigh a portion of Ascorbic Acid

Powder, equivalent to 0.5 g of Ascorbic Acid according
to the labeled amount, add 30 mL of water, shake for 1
minute and filter. Proceed with 5 mL each of the filtrate
as directed in the Identification (1) under Ascorbic Acid.
(2) Weigh a portion of Ascorbic Acid Powder, equivalent to about 10 mg of Ascorbic Acid according to the
labeled amount, add 10 mL of a solution of metaphosphoric acid (1 in 50), shake for 1 minute and filter. Proceed with 5 mL of the filtrate as directed in the Identification (2) under Ascorbic Acid.
Pakaging and Storage Preserve in tight containers.
Purity RancidityAscorbic Acid Powder is free from

any unpleasant or rancid odor and taste.
Method of Preparation Prepare as directed under Tablets, with Ascorbic Acid.
Particle Size Distribution Test for Preparations It

Identification (1) Weigh a portion of powdered Ascorbic Acid Tablets, equivalent to 0.5 g of Ascorbic Acid according to labeled amount, add 30 mL of water, shake for
1 minute and filter. Proceed with 5 mL of the filtrate as
directed in the Identification (1) under Ascorbic Acid.
(2) Pipet 2 mL of the filtrate, add sodium hydroxide
TS to make neutral, then add 2 drops of uranyl acetate
TS: a red brown color develops. And then add 2 mL of
sodium hydroxide TS: a yellow color develops.
(3) Weigh a portion of powdered Ascorbic Acid Tablets, equivalent to 10 mg of Ascorbic Acid according to
labeled amount, add 10 mL of a solution of metaphosphoric acid (1 in 50), shake for 1 minute and filter. Proceed with 5 mL of the filtrate as directed in the Identification (2) under Ascorbic Acid.
Uniformity of Dosage Units (divided) It meets the requirement.

Assay Weigh accurately a portion of Ascorbic Acid
Powder, equivalent to about 0.1 g of ascorbic acid
(C6H8O6) according to the labeled amount, extract with
several successive portions of metaphosphoric acidacetic acid TS, combine the extracts and filter. Wash the
residue with metaphosphoric acid-acetic acid TS. Combine the filtrate and washings and add metaphosphoric
acid-acetic acid to make exactly 200 mL. Pipet exactly 2
mL of this solution and shake with 8 mL of metaphosphoric acid-acetic acid TS and 2 mL of hydrogen peroxide TS. Titrate with 2,6-dichlorophenol-indophenol sodium TS for titration until a light red color persists for 5
seconds. Perform a blank determination and make any
Each mL of 2,6-dichlorophenol-indophenol sodium TS
for titration = A mg of C6H8O6
A is decided by the following standardization of 2,6-
Ascorbic Acid Tablets

Vitamin C Tablets
Ascorbic Acid Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of ascorbic
acid (C6H8O6: 176.12).
Dissolution Test Perform the test with 1 tablet of Ascorbic Acid Tablets at 50 revolutions per minute according to the Method 2 under the Dissolution Test, using
900 mL of the water as the dissolution solution. After 45
minutes from the start of the test, take not less than 20
mL of the dissolution solution and filter the solution using a membrane filter having the pore size of not more
than 0.8 m. Proceed with the filtrate as directed in the
Assay.
The dissolution rate of Ascorbic Acid Tablets in 45 minutes is not less than 75%.
Ascorbic Acid Tablets, equivalent to about 0.1 g of ascorbic acid (C6H8O6) and proceed with this powder as directed in the Assay under Ascorbic Acid Powder.
tight containers.
Aspirin
CO2H
O
O
Acetylsalicylic Acid
CH3
C9H8O4: 180.16
Aspirin, when dried, contains not less than 99.5% and

not more than 101.0% of aspirin (C9H8O4).
Description Aspirin is a white crystal, granule or
powder, is odorless and has a slight acid taste.
Aspirin is freely soluble in ethanol or in acetone, soluble
in ether, and slightly soluble in water.
Aspirin dissolves in sodium hydroxide TS and in sodium
carbonate TS.
In moist air, aspirin gradually hydrolyzes to salicylic acid
and acetic acid.
Melting pointAbout 136 C (bath fluid is heated at
130 C previously).
Identification (1) Boil 0.1 g of Aspirin in 5 mL of water for 5 to 6 minutes, cool. and add 1 to 2 drops of ferric
chloride TS: a red-purple color is produced.
(2) Boil 0.5 g of Aspirin in 10 mL of sodium carbonate TS for 5 minutes and add 10 mL of dilute sulfuric
acid: the odor of acetic acid is perceptible and a white
precipitate is produced. Filter the precipitate, add 3 mL
of ethanol and 3 mL of sulfuric acid to the filtrate and
heat: the odor of ethyl acetate is perceptible.
Purity (1) Clarity of solutionDissolve 0.5 g of Aspirin in 10 mL of warm sodium carbonate TS: the solution
is clear.
(2) Salicylic acidDissolve 2.5 g of Aspirin in ethanol to make 25 mL and add 1.0 mL of this solution to a
solution prepared by transferring 1 mL of a freshly prepared dilute ammonium ferric sulfate TS to a Nessler
tube and diluting with water to make 50 mL. Allow to
stand for 30 seconds: the color of the solution is not more
intense than that of the following control solution.
Control solutionDissolve 0.1 g of salicylic acid in water and add 1 mL of glacial acetic acid and water to make
1000 mL. Add 1.0 mL of this solution to a solution prepared by transferring 1 mL of freshly prepared dilute
ammonium ferric sulfate TS and 1 mL of ethanol to a
Nessler tube and diluting with water to make 50 mL. Allow to stand for 30 seconds.
(3) ChlorideBoil 1.8 g of Aspirin in 75 mL of water for 5 minutes, cool, add water to make 75 mL and filter. To 25 mL of the filtrate, add 6 mL of dilute nitric acid
and water to make 50 mL and perform the test using this
solution as the test solution. Prepare the control solution
with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not
more than 0.015%).
(5) Heavy metalsDissolve 2.5 g of Aspirin in 30
mL of acetone, add 2 mL of dilute acetic acid and water
to make 50 mL and perform the test using this solution as
mL of standard lead solution, 30 mL of acetone, 2 mL of
dilute acetic acid and water to make 50 mL (not more
than 10 ppm).
(6) Readily carbonizable substancesWeigh 0.5 g
of Aspirin and perform the test. The solution has no more
color than Color Matching Fluid Q.
hours).
Assay Weigh accurately about 1.5 g of Aspirin, previously dried, add exactly 50 mL of 0.5 mol/L sodium
hydroxide VS and boil gently for 10 minutes using a reflux condenser closed with a carbon dioxide-absorbing
tube (soda lime). Cool and titrate excess sodium hydroxide with 0.25 mol/L sulfuric acid VS (indicator: 3 drops
of phenolphthalein TS) immediately. Perform a blank determination and make any necessary correction.
= 45.04 mg of C9H8O4
Aspirin Tablets
Acetylsalicylic Acid Tablets
Aspirin Tablets contain not less than 95.0% and not more
than 105.0% of the labeled amount of aspirin (C9H8O4:
180.16).
KP 9 75
Method of Preparation Prepare as directed under Tablets, with Aspirin.

Identification (1) Weigh a portion of powdered Aspirin Tablets, equivalent to 0.1 g of Aspirin according to
the labeled amount, add 10 mL of water and boil for 5 to
6 minutes. After cooling, filter and add 1 to 2 drops of
ferric chloride TS to the filtrate: a red-purple color develops.
(2) Weigh a portion of powdered Aspirin Tablets,
equivalent to 0.5 g of Aspirin according to the labeled
amount, extract with two 10 mL volumes of warm ethanol and filter the combined extracts. Evaporate the filtrate to dryness and boil the residue with 10 mL of sodium carbonate TS for 5 minutes. Proceed as directed in
the Identification (2) under Aspirin.
Purity Salicylic acidWeigh accurately and powder
not less than 20 Aspirin Tablets. Weigh accurately an
amount equivalent to about 1.0 g of Aspirin, add mobile
phase to make 100 mL and use this solution as the test
Salicylic Acid RS, dissolve in mobile phase to make 100
mL. Pipet exactly 5 mL of this solution, add mobile
standard solution. Perform the test with test solution and
the standard solution as directed under Assay (not more
than 0.15%).
Internal standard solutionDissolve about 10 mg of

Theophylline RS in mobile phase to make 100 mL.
Column: A stainless steel column, about 4 mm in inside diameter and between 15 and 30 cm in length,
packed with octadecylsilanized silica gel for liquid
chromatography (between 5 and 10 m in particle diameter).
about 30 C.
Mobile phase: A mixture of 0.085% phosphoric acid
and methanol (60 : 40).
System suitability
with 10 L of the standard solution under the above operating conditions, the internal standard and aspirin are
above operating conditions, the relative standard deviation of the ratio of the peak area is not more than 2.0%.
Disintegration Test It meets the requirement..

Aspirin Tablets. Weigh accurately an amount equivalent
to about 0.25 g of aspirin (C9H8O4), add mobile phase,
shake well, add mobile phase to make 200 mL, then filter.
Discard the first 10 mL of the filtrate, measure exactly 2
mL of subsequent filtrate, add 4.0 mL of internal standard solution and mobile phase to make 100 mL. Use
this solution as the test solution. Separately, weigh accurately about 25 mg of Aspirin RS, previously dried in desiccator (silica gel) for 5 hours, dissolve in mobile phase
to make exactly 20 mL. Pipet exactly 2 mL of this solution, add 4.0 mL of internal standard solution and mobile
phase to make exactly 100 mL, and use this solution as
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS ,
of the peak area of aspirin to that of internal standard, for
Amount (mg) of aspirin (C9H8O4)
= amount (mg) of Aspirin RS
QT
10
QS
Aspirin Aluminum
-
CO2
O
O
CH3
2+
Al (OH)
Aluminum Acetyl Salicylate
C18H15NA1O9: 416.30
Aspirin Aluminum contains not less than 83.0% and not

more than 90.0% of aspirin (C9H8O4: 180.16) and not
less than 6.0% and not more than 7.0% of aluminum (Al:
Description Aspirin Aluminum is a white, crystalline
powder. Aspirin Aluminum is odorless or has a slightly
acetic odor.
Aspirin Aluminum is practically insoluble in water, in
methanol, in ethanol or in ether.
Aspirin Aluminum dissolves, with decomposition, in sodium hydroxide TS or sodium carbonate TS.
Identification (1) Dissolve 0.1 g of Aspirin Aluminum
in 10 mL of sodium hydroxide TS by heating, if necessary. Neutralize 2 mL of this solution with hydrochloric
acid and add 1 to 2 drops of ferric chloride TS: a redpurple color develops.
(2) Determine the absorption spectrum of the test solution obtained in the Assay (1) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 277 nm and 279 nm.
(3) Place 2 g of Aspirin Aluminum in a platinum
crucible and ignite until charred. To the residue, add 1 g
of anhydrous sodium carbonate and ignite for 20 minutes.
After cooling, to the residue, add 15 mL of dilute hydrochloric acid, shake and filter: the filtrate responds to
the Qualitative Tests for aluminum salt.
Purity (1) SalicylateUsing AT2 and AS2 obtained
in the Assay (1), calculate the amount of salicylate [as salicylic acid (C7H6O3: 138.12)] by the following equation:
salicylate content is not more than 7.5%, calculated on
the anhydrous basis.
Amount (mg) of salicylic acid (C7H6O3)
A
= amount (mg) of Salicylic Acid RS T 2 1
AS 2 4
(2) Heavy metalsPlace 2.0 g of Aspirin Aluminum

in a porcelain crucible, cover the crucible loosely and ignite at a low temperature until charred. After cooling, add
2 mL of nitric acid and 1 mL of sulfuric acid to the content of the crucible, heat gently the crucible until white
fumes are evolved and continue the heating until white
fumes are no longer evolved, then ignite between 500 C
and 600 C until the carbon is incinerated. When the incineration is not completed, add 2 mL of nitric acid and 1
mL of sulfuric acid and heat gently in the same manner,
then ignite between 500 C and 600 C to incinerate
completely. After cooling, add 2 mL of hydrochloric acid
and proceed as directed in Method 2 and perform the test.
Prepare the control solution by using the same quantities
of the same reagents as directed for the preparation of the
test solution and add 2.0 mL of standard lead solution
and water to make 50 mL (not more than 10 ppm).
(3) ArsenicDissolve 1.0 g of Aspirin Aluminum in
15 mL of sodium hydroxide TS. To this solution, add 1
drop of phenolphthalein TS and with stirring, add dropwise hydrochloric acid until the red color of the solution
disappears. Then add 2 mL of hydrochloric acid, cool
with occasional shaking for 10 minutes and filter with a
glass filter (G3). Wash the residue with two 5 mL volumes of 1 mol/L hydrochloric acid TS and combine the
filtrate and the washings. Use this solution as the test solution and perform the test (not more than 2 ppm).
with six 20 mL volumes of chloroform. Combine all

chloroform extracts and add chloroform to make exactly
200 mL. Measure exactly 10 mL of this solution, add
chloroform to make exactly 100 mL and use this solution
as the test solution. Separately, weigh accurately about
90 mg of Salicylic Acid RS, previously dried in a desiccator (silica gel) for 3 hours, and dissolve in chloroform
to make exactly 200 mL. Measure exactly 5 mL of this
use this solution as the standard solution (1). Then weigh
accurately about 90 mg of Aspirin RS, previously dried
in a desiccator (silica gel) for 5 hours and dissolve in
chloroform to make exactly 200 mL. Measure exactly 10
mL of this solution, add chloroform to make exactly 100
solutions (1) and (2) as directed under the Ultravioletvisible Spectrophotometry. Determine the absorbances,
AT1 and AS1 , of the test solution and the standard solution (1) at 278 nm and absorbances, AT2 and AS2 , of
the test solution and the standard solution (2), respectively, at 308 nm. Then determine the absorbance, AS3 of
the standard solution (2) at 278 nm.
Amount (mg) of aspirin (C9H8O4)
AT 2 AS1
AS 2
AS 3
AT 1
= amount (mg) of Aspirin RS
(2) AluminumWeigh accurately about 0.4 g of Aspirin Aluminum and dissolve in 10 mL of sodium hydroxide TS. Add drop-wise 1 mol/L hydrochloric acid TS
until the pH of the solution to about 1, add 20 mL of
acetic acid-ammonium acetate buffer solution, pH 3.0
and 0.5 mL of Cu-PAN TS and heat. While boiling, titrate with 0.05 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution changes from red
to yellow and persists for 1 minute. Perform a blank determination and make any necessary correction.
Each mL of 0.05 mol/L disodium ethylenediaminetetraahetate VS = 1.3491 mg of Al
Atenolol
Water Not more than 4.0% (0.15 g, volumetric titration, direct titration).
OH
O
H
N
CH3
Assay (1) AspirinWeigh accurately about 0.1 g of

Aspirin Aluminum, add 40 mL of sodium fluoride TS
and shake for 5 minutes. Allow the solution to stand for
10 minutes with frequent shaking. Extract the solution
CH3
H2N
and enantiomer
KP 9 77
C14H22N2O3: 266.34
Atenolol, when dried, contains not less than 99.0% and
not more than 101.0% of atenolol (C14H22N2O3).
Description Atenolol is a white to pale yellow crystalline powder.
Atenolol is freely soluble in methanol or in glacial acetic
acid, soluble in dehydrated ethanol, and slightly soluble
in water.
A solution of Atenolol in methanol (1 in 25) shows no
optical rotation.
a solution of Atenolol and Atenolol RS, in methanol (5 in
100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wavelengths..
(2) Determine the infrared spectra of Atenolol and
Atenolol RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Melting Point
tetrabutylammonium hydrogensulfate in 1000 mL of this

solution.
time of atenolol is about 8 minutes.
System suitability
Test for required detectability: To exactly 10 mL of
the standard solution add mobile phase to make exactly
50 mL. Confirm that the peak area of atenolol obtained
with 10 L of this solution is equivalent to 14 to 26% of
that obtained with 10 L of the standard solution.
with 10 L of the standard solution under the above operating conditions, the number of theoretical plates and
the symmetry factor of the peak of atenolol are not less
than 5000 and not more than 1.5, respectively.
above operating conditions, the relative standard deviation of the peak area of atenolol is not more than 1.0%.
Time span of measurement: About 4 times as long as the
retention time of atenolol.
hour).

Purity (1) Heavy metalsProceed with 2.0 g of Atenolol according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard lead
(2) Related substances Dissolve 50 mg of Atenolol
in the mobile phase to make 25 mL, and use this solution
as the test solution. Pipet exactly 1 mL of the test solution, add the mobile phase to make 200 mL, and use this
to the following conditions, and determine each peak
area by the automatic integration method: any area peak
other than atenolol obtained with the test solution is not
larger than 1/2 times the peak area of atenolol from the
standard solution, and the total area of all peaks other
than atenolol from the test solution is not larger than the
peak area of atenolol with the standard solution.
diameter and 15 cm in length, packed with octadecysilanized silica gel for liquid chromatography (5 m in particle diameter).
about 25 C.
Mobile phase: Dissolve 3.4 g of potassium dihydrogen phosphate in 1000 mL of water, and adjust to pH 3.0
with phosphoric acid. To 40 volume of this solution add
9 volume of methanol and 1 volume of tetrahydrofuran.
Dissolve 1.0 g of sodium 1-octanesulfonate and 0.4 g of
Assay Weigh accurately about 0.1 g each of Atenolol

and Atenolol RS, previously dried, dissolve separately in
the mobile phase to make exactly 100 mL, respectively.
Pipet exactly 5 mL each of these solutions, add the mobile phase to make exactly 50 mL, pipet exactly 5 mL
each of these solutions again, add the mobile phase to
make exactly 50 mL, and use these solutions as the test
solution and the standard solution respectively. Perform
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate
each peak area of Atenolol, AT and AS , for the test
solution and the standard solution, respectively.
Amount (mg) of atenolol (C14H22N2O3)
= Amount (mg) of Atenolol RS
AT
AS
Mobile phase: Dissolve 1.1 g of sodium 1heptanesulfonate and 0.71 g of anhydrous sodium dihydrogen phosphate in 700 mL of water, add 2 mL of dibutylamine, and adjust the pH to 3.0 with 0.8 mol/L phosphoric acid TS. Add 300 mL of methanol to this solution
and mix well.
System suitability
with 10 L of the standard solution under the above operating conditions, the theoretical plates are not less than
5000 and the symmetry factor is not more than 2.0.
above operating conditions, the relative standard deviation of the ratios of the peak area is not more than 2.0%.
not less than 80%.

Atenolol Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.25 g of atenolol
(C14H22N2O3), add the mobile phase, and sonicate for 15
minutes. Add the mobile phase to make exactly 1000 mL,
centrifuge, pipet exactly 2 mL of the supernatant, add the
mobile phase to make 50 mL, and use this solution as the
test solution. Separately, weigh exactly about 25 mg of
Atenolol RS, add the mobile phase to make 100 mL, pipet exactly 2 mL of this solution, add the mobile phase to
make 50 mL, and use this solution as the standard solution. Perform the test with 10 L each of the test solution
and the standard solution as directed in the Assay under
Atenolol.
Atenolol Tablets
Atenolol tablets contains not less than 90.0% and not
more than 110.0% of the labeled amount of atenolol
(C14H22N2O3: 266.34).
Method of Preparation Prepare as directed under Tablets, with Atenolol.
Identification (1) To a portion of powdered Atenolol
Tablets, equivalent to 0.1 g of Atenolol according to labeled amount, add 15 mL of methanol, mix well, warm
at 50 C, shake for 5 minutes. Filter, evaporate the filtrate
on a water-bath to dryness, add 0.1 mol/L hydrochloric
acid to this residue, shake on warming, and filter. To this
filtrate, add a sufficient amount of 1 mol/L sodium hydroxide TS to make alkaline, extract with 10 mL of chloroform, remove water from the chloroform layer using
anhydrous sodium sulfate, and filter. Evaporate the filtrate to dryness on a water-bath, dry this residue at 105
C for 1 hour, and use this residue as the test sample. Determine the infrared spectra of the test sample and Atenolol RS, powdered finely according to the same method,
as directed in the potassium bromide disk method under
the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(2) The retention time of main peak of the test solution for Assay and the standard solution is the same.
Dissolution Test Perform the test with 1 tablet of Atenolol Tablets at 50 revolutions per minute according to
water as the dissolution solution. Take 20 mL or more of
the dissolve solution 30 minutes after starting the test,
and filter through a membrane filter with pore size of not
more than 0.8 m. Add phosphoric acid solution (1 in
1000) to this filtrate so that each mL contains 10 g of
Atenolol, and use this solution as the test solution. Determine the absorbances, AT and AS , of the test solution and the standard solution, prepared according to the
Assay, respectively, as directed in the Assay.
The dissolution rate of Atenolol Tablets in 30 minutes is

of Atenolol (C14H22N2O3) = 900 C D AT
AS
C: Concentration of Atenolol in the standard solution

(mg/mL).
D: Dilution times of the test solution.
Amount (mg) of atenolol (C14H22N2O3)

= amount (mg) of Atenolol RS AT 10
AS
Atracurium Besylate
O
O S
O-
. 2
H3CO
OCH3
OCH3
H3CO
N
H3CO
H3CO
CH3
O
O
N
CH3
OCH3
OCH3
C53H72N2O122C6H5O3S2 : 1243.48
Atracurium Besylate contains not less than 96.0% and
not more than 102.0% of atracurium besylate
(C53H72N2O122C6H5O3S2), calculated on the anhydrous
basis.
Description Atracurium Besylate is a white to yellowish-white solid.
Atracurium Besylate is very soluble in dichloromethane,
in acetonitrile, or in ethanol and soluble in water.
Atracurium Besylate is hygroscopic.
Identification
(1) Determine the infrared spectra of
KP 9 79
Atracurium Besylate and Atracurium Besylate RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) The 3 principal isomeric peaks from test solution
are same in retention time as those from standard solution in Assary.
Purity (1) Heavy metalsProceed with 1.0 g of Atracurium Besylate according to Method 2 and perform the
(2) Methyl benzenesulfonateWeigh exactly 0.10 g
of Atracurium Besylate, dissolve mobile phase A to
make exactly 10 mL and use this solution as the test solution. Separately, weigh exactly 20.0 mg of Atracurium
Besylate RS, add acetonitrile to make exactly 100 mL,
pipet 1.0 mL of this solution and add solution A to make
exactly 200 mL and use this solution as the standard solution. Perform the test with 100 L of the test solution
and the standard solution as directed under Liquid
Chromatography according to the following conditions
and measure the responses for the methyl benzenesulfonate peaks: the peak area from the test solution is not
greater than that from the standard solution (0.01%).
base-deactivated octadecylsilanized silica gel for Liquid
Chromatography (5 m in particle diameter).
Mobile phase: The chromatograph is programmed as
follows with mobile phase A and mobile phase B.
Mobile phase A and mobile phase BPrepare as
directed in the Assay.
Time
(minutes)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
80
20
0~5
5 ~ 15
15 ~ 25
25 ~ 30
80
80 75
75
75 55
20
20 25
25
25 45
Isocratic
Linear gradient
Isocratic
Linear gradient
30 ~ 38
55 0
45 100
Linear gradient
38 ~ 45
100
Elution
Equilibration
isocratic

System suitability
System performance: Pipet 1 mL of the test solution and 5 mL of 0.02% methyl benzenesulfonate in acetonitrile and add mobile phase to make 100 mL. When
the procedure is run with this solution under the above
operating condition, the resolution between the transtrans isomer and methyl benzenesulfonate is not less than
12.0.
times with the standard solution under the above operating conditions, the responses for duplicate injections do
not differ from each other by more than 12%.
(3) TolueneWeigh accurately about 0.20 g of Atracurium Besylate, dissolve in acetonitrile to make exactly
10 mL and use this solution as the test solution. Separately, weigh accurately 0.1 g of Atracurium Besylate RS,
dissolve in acetonitrile to make exactly 100 mL, pipet 5.0
mL of this solution, add acetonitrile to make exactly 50
mL and use this solution as the standard solution. Perform the test with 1 L of the test solution and the standard solution as directed under Gas Chromatography according to the following conditions and measure the responses for the major peaks: the area of toluene peak from
the test solution is not greater than that from the standard
solution (not more than 0.5%).
Column: A fused-silica analytical column 0.53 mm in
inside diameter and 30 m in length, coated the inner surface with 5% phenyl-95% methyl polysiloxane for Gas
Chromatography 5 m in thickness. A fused-silica guard
column 0.53 mm in inside diameter and 5 m in length,
coated the inner surface with deactivated with phenylmethyl siloxane.
Column temperature: Program as follows; Initially,
the column temperature is maintained at 35 C for 5 minutes, then increased at a rate of 8 C per minute to 175
C, followed by an increase at a rate of 35 C per minutes
to 260 C, and maintained at 260 C for at least 16 minutes.
about 70 C.
about 260 C.
Carrier gas: Helium
Flow rate: 35 mL/second
System suitability
System performance: Weigh accurately each of
dichloromethane, dioxane, trichloroethylene, and chloroform and dissolve in acetonitrile to make the solution
that contains 12.0, 7.6, 1.6, and 1.2 g per mL, respectively. When the procedure is run with 1 L of this solution under the above operating conditions, the resolution
between two peaks is not less than 1.0.
System repeatability: Weigh accurately each of
dichloromethane, dioxane, trichloroethylene, and chloroform and dissolve in acetonitrile to make the solution
that contains 12.0, 7.6, 1.6, and 1.2 g per mL, respectively. When the procedure is run with 1 L of this solution under the above operating conditions, the relative
standard deviation of each peak area is not more than
15%.
(4) Related substancesUse the test solution of the
Assay as the test solution. To 1.0 mL of the standard solution of the Assay add mobile phase A of the Assay to
make 100 mL and use this solution as the standard solution. Perform the test with 20 L of the test solution and
the standard solution as directed under Liquid Chromatography according to the following conditions and
measure all the peak areas, except the three main isomeric peaks. Calculate the percentage of each related substances in the portion of Atracurium Besylate taken by
the formula: indiridual impurity is not more than 1.0%
and total impurities is mot more than 3.5%.
A
Amount (%) of each impurity = 10000 C i
W
AS
Ai :the peak area for each related substances obtained

from the test solution
AS :the peak area for the cis-cis isomer obtained
from the standard solution
W:the weight of Atracurium Besylate taken to prepare the test solution (mg)
C:the concentration of the cis-cis isomer in the standard solution (mg/mL)
System suitability
When the test is repeated more than 2 times with
20 L of the standard solution under the operating conditions of the Assay, the difference of the peak area of ciscis isomer is not more than 10%.
direct titration)
Assay Weigh accurately about 0.1 g each of Atracurium Besylate and Atracurium Besylate RS, dissolve in
mobile phase A to make exactly 100 mL and use the solutions as the test solution and the standard solution, respectively. Perform the test with exactly 20 L each of
the test solution and the standard solution as directed under Liquid Chromatography according to the following
conditions, and determine total area, AT and AS , of
the three isomeric peaks, respectively.
Mobile phase: Program as follows with the mobile

phase A and the mobile phase B in isocratic or in linear
gradient.
Mobile phase A: The mixture of buffer solution, acetonitrile and methanol (75 : 20 : 5)
Mobile phase B: The mixture of buffer solution, methanol and acetonitrile (50 : 30 : 20)
Time
(minutes)
0
0~5
5 ~ 15
15 ~25
25 ~30
Mobile
phase A
(%)
80
80
80 40
40
40 0
= amount (mg) of Atracurium Besylate RS
Elution
Equilibration
Isocratic
Linear gradient
Isocratic
Linear gradient

System suitability
with the standard solution under the above operating
condition, the relative retention times are about 0.8, 0.9,
and 1.0 for the trans-trans isomer, the cis-trans isomer,
and the cis-cis isomer, respectively. The resolution between the trans-trans isomer and the cis-trans isomer
and between the cis-trans isomer and the cis-cis isomer
is not less than 1.1.
times with the standard solution under the above operating conditions, the relative standard deviation of the peak
area of each isomer is not more than 2.0%.
Buffer solutionWeigh about 10.2 g of monobasic
potassium phosphate, and dissolve in about 950 mL of
water, while stirring, adjust with phosphoric acid to a pH
of 3.1, add water to make 1000 mL.
tight containers. Store at a temperature of 2 C to 8 C.
Atropine Sulfate Hydrate

H
O
O
Amount (mg) of atracurium besylate

(C53H72N2O122C6H5O3S2)
Mobile
phase B
(%)
20
20
20 60
60
60 100
CH
H2SO4
NCH3
H
AT
AS
H2O
CH2OH
2
[(C17H23NO3)2.H2SO4H2O: 694. 83]

base-deactivated octadecylsilanized silica gel for Liquid
Chromatography (5 to 10 m in particle diameter).
Atropine Sulfate Hydrate, when dried, contains not less

than 98.0% and not more than 101.0% of atropine sulfate
[(C17H23NO3)2H2SO4: 676.82]
Description Atropine Sulfate Hydrate is a colorless
crystals or a white, crystalline powder and is odorless.
KP 9 81
Atropine Sulfate Hydrate is very soluble in water or in
glacial acetic acid, freely soluble in ethanol and practically insoluble in ether.
Melting pointBetween 188 C and 194 C (with
decomposition). Introduce a capillary tube charged with
dried sample into a bath previously heated to 180 C and
continue to heat at the rate of rise of about 3 C per
minute.
Atropine Sulfate Hydrate is affected by light.
Identification (1) To 1 mg of Atropine Sulfate Hydrate,
add 3 drops of fuming nitric acid and evaporate the mixture in a water-bath to dryness. Dissolve the residue in 1
mL dimethylformamide and add 5 to 6 drops of tetraethylammonium hydroxide TS: a red-purple color develops.
(2) To 2 mL of a solution of Atropine Sulfate Hydrate
(1 in 50), add 4 to 5 drops of hydrogen tetrachloroaurate
TS: a lusterless, yellowish white precipitate is formed.
(3) To 5 mL of a solution of Atropine Sulfate Hydrate
(1 in 25), add 2 mL of ammonia TS and allow to stand
for 2 to 3 minutes. Collect the precipitate, wash with water and dry in a desiccator (in vacuum, silica gel) for 4
(4) A solution of Atropine Sulfate Hydrate (1 in 20)
responds to the Qualitative Tests for sulfate.
g of Atropine Sulfate Hydrate in 10 mL of water: the solution is clear and colorless.
(2) AcidDissolve 1.0 g of Atropine Sulfate Hydrate
in 20 mL of water and add 0.30 mL of 0.02 mol/L sodium hydroxide VS and 1 drop of methyl red-methylene
blue TS: a green color develops.
(3) Related SubstancesDissolve 0.25 g of Atropine
Sulfate Hydrate in 1 mL of diluted hydrochloric acid (1
in 10), add water to make 15 mL and use this solution as
the test solution. (i) To 5 mL of the test solution, add 2 to
3 drops of chloroplatinic acid TS: no precipitate is
formed. (ii) To 5 mL of the test solution, add 2 mL of
ammonia TS and shake vigorously: the turbidity of the
solution is not greater than that of the following control
solution.
Control solutionTo 0.30 mL of 0.01 mol/L hydrochloric acid VS, add 6 mL of dilute nitric acid and water to
make 50 mL. To this solution, add 1 mL of silver nitrate
TS and allow 7 mL of the mixture to stand for 5 minutes.
(4) HyoscyamineWeigh accurately about 1 g of
Atropine Sulfate Hydrate, previously dried and dissolve
in water to make exactly 10 mL: the specific optical rotation [ ]20
D of this solution in a 100 mm cell is between 0.60 and +0.10.
(5) Readily carbonizable substancesTake 0.20 g of
Atropine Sulfate Hydrate and perform the test: the solution has no more color than Color Matching Fluid A.

P2O5, 110 C, 4 hours).
Assay Dissolve about 0.25 g of Atropine Sulfate Hydrate, previously dried and accurately weighed, in 30 mL
of glacial acetic acid. If necessary, dissolve by warming
and cool. Titrate with 0.05 mol/L perchloric acid VS until
the color of the solution changes from purple through
blue to blue-green (indicator: 3 drops of methylrosaniline
chloride TS). Perform a blank determination and make
= 33.841 mg of (C17H23NO3)2H2SO4
tight containers.
Atropine Sulfate Injection

Atropine Sulfate Injection is an aqueous solution for injection. Atropine Sulfate Injection contains not less than
of atropine sulfate hydrate [(C17H23NO3)2H2SO4H2O:
694.83].
Method of Preparation Prepare as directed under Injections, with Atropine Sulfate Hydrate.
Description Atropine Sulfate Injection is a clear, colorless liquid.
Identification (1) Evaporate a volume of Atropine Sulfate Injection, equivalent to 1 mg of Atropine Sulfate
Hydrate according to the labeled amount, in a water-bath
to dryness. Proceed with the residue as directed in the
Identification (1) under Atropine Sulfate Hydrate.
(2) Evaporate an exactly measured volume of Atropine Sulfate Injection, equivalent to 5 mg of Atropine
Sulfate Hydrate according to the labeled amount, on a
water bath to dryness. After cooling, dissolve the residue
in 1 mL of ethanol, and use this solution as the test solution. If insoluble substance remains, crush it, allow to
stand, and use the supernatant liquid as the test solution.
Separately, dissolve 10 mg of Atropine Sulfate Hydrate
RS in 2 mL of ethanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot 5 L each
plate with a mixture of acetone, water and strong ammonia water (90 : 7 : 3) to a distance of about 10 cm, and
dry the plate at 80 C for 10 minutes. After cooling, spray
evenly Dragendorffs TS for spraying on the plate: the
spots obtained from the test solution and the standard solution show an orange color and the same Rf value.
(3) Atropine Sulfate Injection responds to the Qualitative Tests for sulfate.
Bacterial Endotoxins Less than 75 EU/mg of Atropine
Sulfate Hydrate
It

Assay To an exactly measured volume of Atropine Sulfate Injection, equivalent to about 5 mg of atropine sulfate hydrate [(C17H23NO3)2H2SO4H2O], add exactly 3
mL of the internal standard solution and water to make
50 mL and use this solution as the test solution. Separately, weigh accurately about 25 mg of Atropine Sulfate
Hydrate RS (determine previously its loss on drying in
the same manner as directed under Atropine Sulfate Hydrate), and add water to make exactly 50 mL. Pipet exactly 10 mL of this solution, add 3 mL of internal standard solution and water to make 50 mL, and use this solution as the standard solution. Perform the test with 20
following conditions, and determine the ratios, QT and
QS , of the peak area of atropine to that of the internal

standard for the test solution and the standard solution.
Amount (mg) of atropine sulfate hydrate
[(C17H23NO3)2 H2SO4H2O]
= WS
QT 1
1 .0266
QS 5
WS : Amount of Atropine Sulfate RS, calculated based

on the dried basis (mg)
Internal standard solutionA solution of etilefrine hydrochloride (1 in 1000).
Detector: A ultraviolet absorption photometer (wavelength: 210 nm).
diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
about 40 C.
Mobile phase: To 0.4 g of sodium lauryl sulfate add

500 mL of diluted phosphoric acid (1 in 1000) to dissolve, and adjust the pH to 3.0 with sodium hydroxide
TS. To 240 mL of this solution add 70 mL of tetrahydrofuran, and mix.
time of atropine is about 16 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, the internal standard and atropine are
eluted in this order with the resolutions between these
above operating conditions, the relative standard deviations of the ratio of the peak area of atropine to that of
the internal standard is not more than 1.5%.
Atropine Sulfate Tablets

Atropine Sulfate Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of atropine
sulfate hydrate [(C17H23NO3)2H2SO4 H2O: 694.83].
Method of Preparation Prepare as directed under Tablets, with Atropine Sulfate hydrate.
Identification (1) Weigh a portion of finely powdered
Atropine Sulfate Tablets, equivalent to about 1 mg of
Atropine Sulfate Hydrate according to the labeled
amount, add 1 drop of strong ammonium hydroxide and
2 mL of chloroform, mix, separate the chloroform layer
and evaporate the chloroform on a water-bath. Proceed
with the residue as directed in the Identification (1) under
Atropine Sulfate hydrate.
(2) Weigh a portion of finely powdered Atropine Sulfate Tablets, equivalent to about 5 mg of Atropine Sulfate
Hydrate according to the labeled amount, shake with 5
mL of methanol, filter through glass filter (G4) and use
this filtrate as the test solution. Separately, weigh accurately about 50 mg of Atropine Sulfate Hydrate RS, add
ethanol to make exactly 10 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer Chromatography. Spot 50 L of the test solution
and 10 L of the standard solution on a plate of silica gel
for thin-layer chromatography. Develop the chromatogram with a mixture of chloroform and diethyl amine (9 :
1) to a distance of about 10 cm and air-dry the plate.
Spray evenly chloroplatinic acid-potassium iodide TS on
the plate: the spots obtained from the test solution and
the standard solution show a purple color and the same
KP 9 83
Rf value.
(3) Atropine Sulfate Tablets respond to the Qualitative Tests for sulfate.
Disintegration Test It meets the requirement, provided
that the time limit of the test is 15 minutes.
Atropine Sulfate Tablets. Weigh accurately a portion of
the powder, equivalent to about 1 mg of atropine sulfate
hydrate [(C17H23NO3)2H2SO4H2O], transfer to a separator in 5 mL of a pH 9.0 buffer solution and add 2.0 mL of
the internal standard solution. Adjust with 1 mol/L sodium hydroxide to a pH of 9.0 and extract with two 10
mL volumes of dichloromethane. Filter the dichloromethane layer through 1 g of anhydrous sodium sulfate on a
pledget of absorbent cotton, evaporate the filtrate with
the aid of nitrogen current to dryness, dissolve the residue in 2.0 mL of dichloromethane and use this solution
10 mg of Atropine Sulfate Hydrate RS, previously dried
at 120 C for 4 hours and dissolve in water to make exactly 100 mL. Prepare this solution before use. Transfer
exact 10 mL of this solution to a separator, add 2.0 mL of
the internal standard solution and 5.0 mL of a pH 9.0
buffer solution and adjust to a pH of 9.0 with 1 mol/L
sodium hydroxide. Extract with two 10 mL volumes of
dichloromethane, filter the extracts through 1 g of anhydrous sodium sulfate on a pledget of absorbent cotton,
evaporate the filtrate with the aid of nitrogen current to
dryness, dissolve the residue in 2.0 mL of dichloromethane and use this solution as the standard solution. Perform the test with 1 L each of the test and the standard
solution as directed under the Gas Chromatography according to the following conditions and calculate the ratios, QT and QS , of the peak area of atropine sulfate
to that of the internal standard for the test solution and
the standard solution, respectively.
Amount (mg) of atropine sulfate hydrate
[(C17H23NO3)2 H2SO4H2O]
= Amount (mg) of Atropine Sulfate Hydrate
RS
1 QT
1.0266
10 QS
Internal standard solutionAn aqueous solution of

Homatropine Hydrobromide (5 in 100000). Prepare this
solution before use.
Column: A glass column, about 2 mm in inside diameter and about 1.8 m in length, having 50% phenyland 50% methyl-polysiloxane coated at the ratio of 3%
on siliceous earth.
Column temperature: About 225 C.

System suitability
with 1 L of the standard solution under the above operating conditions with the resolution. being not less than
4.0 and with the symmetry factor being not more than
2.0.
operating conditions,the relative standard deviation of
the ratio of the peak area is not more than 2.0%.
pH 9.0 Phosphate buffer solutionDissolve 34.8 g
of dibasic potassium phosphate in 900 mL of water and
adjust to pH 9.0 with 3 mol/L hydrochloric acid or 1
mol/L sodium hydroxide solution.
tight containers.
Azathioprine
N
NO2
N
S
H3C
H
N
C9H7N7O2S: 277.26
Azathioprine, when dried, contains not less than 98.5%
and not more than 101.0% of azathioprine (C9H7N7O2S).
Description Azathioprine is a pale yellow crystal or
crystalline powder and is odorless.
Azathioprine is sparingly soluble in dimethylformamide
or in pyridine, very slightly soluble in water or in dehydrated ethanol, and practically insoluble in chloroform or
in ether.
Azathioprine dissolves in sodium hydroxide TS or in
ammonia TS.
Azathioprine is gradually colored by light.
Identification (1) Dissolve 10 mg of Azathioprine in
50 mL of water by warming. To 5 mL of this solution,
add 1 mL of dilute hydrochloric acid and 10 mg of zinc
powder and allow to stand for 5 minutes: a yellow color
is produced. Filter this solution: the filtrate responds to
the Qualitative Tests for primary aromatic amines and a
red color is produced.
(2) Dissolve 10 mg of Azathioprine in 50 mL of water by warming. To 1 mL of this solution, add 0.5 mL of
phosphotungstic acid TS and 0.5 mL of dilute hydroch-
loric acid: a white precipitate is formed.
(3) Prepare the test solution by proceeding with 30
mg of Azathioprine according to the Oxygen Flask Combustion Method, using 20 mL of water as the absorbing
liquid: the test solution responds to the Qualitative Tests
(1) for sulfate.
(4) Dissolve 10 mg of Azathioprine in 100 mL of 2
mol/L hydrochloric acid TS. To 5 mL of this solution,
add water to make 50 mL and determine the absorption
spectrum of this solution as directed under the Ultraviolet-visible Spectrophotomtry: it exhibits a maximum between 278 nm and 282 nm.
Purity (1) Clarity and color of solutionDissolve 0.5 g
of Azathioprine in 50 mL of dimethylformamide: the solution is clear and shows a pale yellow color.
(2) Acid or alkaliAdd 100 mL of water to 2.0 g of
Azathioprine, shake well for 15 minutes, centrifuge for 5
minutes at 10000 revolutions per minute and filter. Discard the first 20 mL of the filtrate, add 2 drops of methyl
red TS to 40 mL of the subsequent filtrate and use this
solution as the test solution. (i) Add 0.10 mL of 0.02
mol/L hydrochloric acid VS to 20 mL of the test solution:
a red color develops. (ii) Add 0.10 mL of 0.02 mol/L sodium hydroxide VS to 20 mL of the test solution: a yellow color develops.
solution. Prepare the control solution with 0.40 mL of
(4) Heavy metalsProceed with 2.0 g of Azathioprine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Azathioprine, according to Method 3 and perform the
test (not more than 2 ppm).
(6) Related substancesDissolve 10 mg of Azathioprine in 80 mL of the mobile phase by warming, cool,
add the mobile phase to make 100 mL and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add water to make exactly 100 mL and use this
both solutions by the automatic integration method: the
total area of all peaks other than that of Azathioprine
from the test solution is not larger than 1/2 of the peak
area of Azathioprine from the standard solution.

about 40 C.
Mobile phase: Adjust to a pH of 2.5 by adding diluted phosphoric acid (3 in 2000) to diluted 0.05 mol/L
monobasic potassium phosphate TS (1 in 2). To 800 mL
of this solution, add 200 mL of methanol.
time of Azathioprine is about 8 minutes.
System suitability
System performance: Dissolve 10 mg of Azathioprine in 80 mL of water by warming, cool and add water
to make 100 mL. To 2 mL of this solution add 2 mL of a
solution, separately prepared by dissolving 60 mg of
benzoic acid in 3 mL of methanol and diluting with water
to make 10 mL, and add the mobile phase to make 25
mL. When the procedure is run with 20 L of this solution under the above operating conditions, azathioprine
and benzoic acid are eluted in this order with the resolution between their peaks being not less than 9.
times with 20 L of this solution under the above operating conditions, the relative standard of the peak areas of
azathioprine is not more than 2.0%.
Detection sensitivity: To exactly 5 mL of the standard solution add water to make exactly 50 mL. Adjust
the detection sensitivity so that the peak area of azathioprine obtained from 20 L of this solution is between 8
and 12% of that of azathioprine obtained from 20L of
Time span of measurement: About three times as
long as the retention time of Azathioprine after the solvent peak.
hours).
Assay Weigh accurately about 0.5 g of Azathioprine,
previously dried, add 80 mL of dimethylformamide and
warm to dissolve. After cooling, titrate with 0.1 mol/L tetramethylammonium hydroxide VS until the color of the
solution changes from yellow through yellow-green to
blue-green (indicator: 1 mL of thymol bluedimethylformamide TS). Perform a blank determination
hydroxide VS = 27.726 mg of C9H7N7O2S
KP 9 85
Azathioprine Tablets
Azathioprine Tablets contain not less than 95.0% and not
more than 105.0% of the labeled amount of azathioprine
(C9H7N7O2S: 277.26).
Method of Preparation Prepare as directed under Tablets, with Azathioprine.
Identification (1) Weigh a quantity of powdered Azathioprine Tablets, equivalent to 10 mg of Azathioprine
according to the labeled amount. Add 50 mL of water,
shake well while warming and filter. Proceed with 5 mL
of the filtrate as directed in the Identification (1) under
Azathioprine.
(2) Proceed with 1 mL of the filtrate obtained in (1)
as directed in the Identification (2) under Azathioprine.
(3) Determine the absorption spectrum of the test solution in the Assay as directed under the Ultravioletvisible Spectrophotometry: it exhibits a maximum between 278 nm and 282 nm.
(4) Weigh a portion of powdered Azathioprine Tablets, equivalent to 0.1 g of Azathioprine to the labeled
amount. Add 10 mL of a solution of strong ammonia water in methanol (1 in 10), shake well, filter and use the
filtrate as the test solution. Separately, dissolve 0.1 g of
Azathioprine RS in 10 mL of a solution of strong ammonia water in methanol (1 in 10) and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer Chromatography. Spot 5 L each of the test solution and the standard solution on a plate of silica gel with
fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, a solution
of strong ammonia water in methanol (1 in 10), n-butyl
formate and 1,2-dichloroethane (15 : 10 : 5 : 2) to a distance of about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the
spots from the test solution and the standard solution
show the same Rf value.
Disintegration Test It meets the requirement.
Azathioprine Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of azathioprine
(C9H7N7O2S), add 20 mL of dimethylsulfoxide for Spectrophotometry, shake well, add 0.1 mol/L hydrochloric
acid TS to make exactly 500 mL and filter. Discard the
first 20 mL of the filtrate, measure exactly 3 mL of the
subsequent filtrate, add 0.1 mol/L hydrochloric acid TS
to make exactly 100 mL and use this solution as the test
solution. Separately, weigh accurately about 0.1 g of
Azathioprine RS, previously dried at 105 C for 5 hours,
dissolve in 20 mL of dimethylsulfoxide for spectrophotometry and add 0.1 mol/L hydrochloric acid TS to make
exactly 500 mL. Measure exactly 3 mL of this solution,
add 0.1 mol/L hydrochloric acid TS to make exactly 100
mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution
and the standard solution at 280 nm, respectively as directed under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of azathioprine (C9H7N7O2S)
= amount (mg) of Azathioprine RS
AT
AS

tight containers.
Azelastine Hydrochloride
O
NCH3
H
N
N
HCl
Cl
and enantioner
C22H24ClN3OHCl : 418.36
Azelastine Hydrochloride contains not less than 98.5%
and not more than 101.0% of azelastine hydrochloride
(C22H24ClN3OHCl), calculated on the dried basis.
Description Azelastine Hydrochloride is a white crystalline powder.
Azelastine Hydrochloride is soluble in anhydrous ethanol,
slightly soluble in water, and practically insoluble in ether, in n-hexane, or in toluene.
Azelastine Hydrochloride and Azelastine Hydrochloride
RS, previously dried, as directed under the Infrared
(2) A solution of Azelastine Hydrochloride in water
(1 in 50) responds to the Qualitative Tests for chlorides.
+0.50 (previously dried, 1.0 g, dichloromethane, 20 mL,
100 mm)
Purity (1) Acidity or alkalinityTo 10 ml of solution

of Azelastine Hydrochloride in water (1 in 100) add 0.2
ml of bromthymol blue solution. Not more than 0.1 mL
of 0.1 mol/L hydrochloric acid VS or 0.1 mol/L sodium
hydroxide VS is required to change the color of the solution.
(2)
1-Methyl-4-(2-benzoylhydrazino)azepane
Weigh accurately 0.1 g of Azelastine Hydrochloride and
dissolve in 12 mL of methanol and add water to make
exactly 20 mL and use this solution as the test solution.
Separately, weigh accurately 5.0 mg of 1-Methyl-4-(2benzoylhydrazino)azepane Hydrochloride RS and dissolve in 60% methanol to exactly 100 mL. Pipet 5.0 mL
of this solution and dilute in 60% methanol to make exactly 50 mL and use this solution as the standard solution.
Perform the test with 10 L of the test solution and the
standard solution as directed under Liquid Chromatography according to the following conditions, and determine
each peak area by the automatic integration method: the
area of the peak of 1-methyl-4-(2-benzoylhydrazino)
azepane from the test solution is not larger than that of
principal peak from the standard solution. (not more than
0.1%)
Mobile phase: A 0.02 mol/L solution of sodium octanesulfonate in the mixture of methanol, water and anhydrous acetic acid (60 : 40 : 1).
and dry the plate for 1 hour at 115 C. After cooling examine under ultraviolet light (main wavelength: 254 nm)
and spray potassium bithmus iodide TS and then 5 w/v%
solution of sodium nitrous : Two spots of related substances obtained with the test solution are not darker than
each spot from the standard solutions (2) and (3) (0.1%);
those spots and spots other than principal spot are not
darker than spots from the standard solution (1) (0.1%).
Disregard the spot remaining on the origin of the plate.
Loss on Drying Not more than 1.0% (1g, 105 C, constant mass).
Assay Weigh accurately about 0.3 g of Azelastine Hydrochloride, dissolve in 5 ml of anhydrous formic acid,
add 30 ml of acetic anhydride and titrate quickly with 0.1
= 41.84 mg of C22H24ClN3OHCl

tight containers.
Azithromycin Hydrate
H3C
N
H3C
CH3
OH
HO
OH
H3C
(3) Related substancesWeigh accurately 0.5 g of

Azelastine Hydrochloride and dissolve in the mixture of
methanol and dichloromethane (1 : 1) to make exactly 10
mL and use this solution as the test solution. Pipet exactly 0.1 mL of the test solution and add the mixture of methanol and dichloromethane (1 : 1) to make exactly 100
mL and use this solution as standard solution (1). Separately, weigh accurately 5 mg of 4-chlorobenzylprazi
none, dissolve in the mixture of methanol and dichloromethane (1 : 1) to make exactly 100 mL and use this solution as the standard solution (2). Also weigh accurately
5 mg of 1-Methylazepan-4-one Hydrochloride RS, dissolve in the mixture of methanol and dichloromethane
(1 : 1) to make exactly 100 mL and use this solution as
the standard solution (3). Perform the test with these solutions as directed under Thin Layer Chromatography
according to the following conditions. Spot 10 L each
of the test solution, the standard solutions (1), (2), and
(3) on a plate coated with silica gel with fluorescent indicator for thin layer chromatography. Develop the plate
with the mixture of toluene, ethanol and 10 mol/L ammonia water (60 : 40 : 1) to a distance of about 10 cm
CH3
HO
H3C
CH3
H3C
CH3
CH3
CH3
2H2O
CH3
CH3
OH
O
CH3
C38H72N2O122H2O: 785.02
Azithromycin Hydrate contains not less than 950 g (potency) and not more than 1030 g (potency) per mg of
azithromycin (C38H72N2O12: 748.98), calculated on the
anhydrous basis.
Description Azithromycin Hydrate is a white to
grayish white crystalline powder.
Azithromycin Hydrate is freely soluble in acetonitrile, in
dimethylformamide, in methanol, in ethanol, in acetone,
in isopropanol, in ethylacetate, or in chloroform.
Azithromycin Hydrate and Azithromycin Hydrate RS, as
KP 9 87
Infrared spectrophotometry: both spectra exhibit similar
intensities of absorption at the same wave numbers.
(2) Determine the retention times according to the
procedure of Assay: the retention time of the principal
peak in the chromatogram obtained with test solution is
the same as that of the principal peak in the chromatogram obtained with the standard solution.
D : -45 ~ -49(0.2 g calculated on the anhydrous basis, dehydrated ethanol, 10
mL, 100 mm).
of Azithromycin Hydrate in 10 mL of 50 % methanol solution is between 9.0 and 11.0.
Purity (1) Heavy metalsProceed with 2.0 g of Azithromycin Hydrate to Method 2 and perform the test. Prepare the control solution with 5.0 mL of standard lead solution (not more than 25 ppm).
(2) Total related substancesPerform the test according to the procedure of Assay. Prepare the test solution and as follows. Weigh accurately about 33 mg of
Azithromycin Hydrate, dissolve in 5 mL of acetonitrile,
add the mixture of 0.02 mol/L potassium dihydrogen
phosphate solution and acetonitrile (71:29), pH 8.0 adjusted with 10 mol/L potassium hydroxide to make 100
mL, and use this solution as the test solution. Perform the
test with 50 L of the test solution as directed under the
Liquid Chromatography according to the following operating conditions, and obtain the peak areas of azithromycin and each related substance (not more than 5.0 %).
Amount [%] of total related substances
total peak areas other than the principal peak
=
100
total peak areas
Mobile phase: Adjust the pH of the mixture of 0.02
mol/L of potassium dihydrogen phosphate solution and
acetonitrile (75:25) to 11.0 with 10 mol/L potassium hydroxide TS.
Time span of measurement: About 80 minutes.
(3) Erythromycin A iminoetherWeigh accurately
an appropriate amount of Azithromycin Hydrate, dissolve in the mixture of methanol and chloroform (1:1) to
make the solution so that each mL contains 25 mg, and
use this solution as the test solution. Separately, weigh
accurately 2.5 mg (potency) of Erythromycin A iminoether RS, dissolve in the mixture of methanol and
chloroform (1:1), to make the solution so that each mL
contains 0.125 mg, and use this solution as the standard
solution. Perform the test with these solutions as directed
under Thin-layer Chromatography. Spot 50 L of each
solution on a plate of silica gel with fluorescent indicator
for thin-layer chromatography, develop the plate with the

mixture of ethylacetate, hexane and diethylamine
(15:5:2) as the developing solvent mixture, and heat the
plate at 100 C for 10 minutes. Spray evenly the color
developing solution on the plate and heat the plate at 100
C. The color developing solution mixture is prepared by
dissolving 3 g of vaniline in 100 mL of ethanol and adding 1.5 mL of sulfuric acid. The spots other than the
principal spot obtained from the test solution are not
more intense than the principal spot from the standard
solution.
Water Not less than 4.0 % and not more than 5.0 %
Azithromycin Hydrate and Azithromycin Hydrate RS,
dissolve each in acetonitrile to make exactly 200 mL, pipet exactly 2 mL each of these solutions, add the internal
standard solution to make exactly 100 mL, and use these
respectively. Perform the test with 50 L each of the test
Liquid Chromatography according to the following operating conditions, and determine the ratios, QT and QS, of
the peak area of azithromycin to that of the internal standard.
Amount [g (potency)] of azithromycin (C38H72N2O12)
= Amount [g (potency)] of Azithromycin Hydrate RS
QT
QS
Internal standard solutionWeigh accurately 1.5 mg

of diphenhydramine hydrochloride, dissolve in the mixture of 0.02 mol/L potassium dihydrogen phosphate solution and acetonitrile (71:29), pH 8.0 adjusted with 10
mol/L potassium hydroxide to make 1000mL
Detector: An electrochemical detector
alumina based hydrocarbon for liquid chromatography
Mobile phase: Adjust pH of the mixture of 0.02
mol/L potassium dihydrogen phosphate solution and acetonitrile (71:29) to pH 11.0 with 10 mol/L potassium hydroxide.
Flow rate: 1.5 mL per minute
Bacampicillin Hydrochloride
O
CH3
O
CH3
O
N
CH3
CH3
N
H
H2N
S
H
HCl
C21H27N3O7SHCl: 501.98
Bacampicillin Hydrochloride contains not less than ampicillin (C16H19N3O4S: 349.41) 626 g (potency) per mg
of Bacampicillin Hydrochloride, calculated on the anhydrous basis.
Description Bacampicillin Hydrochloride is white to
pale yellow crystalline powder, and has a characteristic
odor and bitter taste.
Bacampicillin Hydrochloride is freely soluble in methanol or in ehtanol, soluble in water, and practically insoluble in ether.
Bacampicillin Hydrochloride and Bacampicillin Hydrochloride RS, as directed in the potassium bromide
disk method under the Infrared spectrophotometry: both
same wavenumbers.
(2) Weigh an appropriate amount each of Bacampicillin Hydrochloride and Bacampicillin Hydrochloride
RS, dissolve in ethanol and make solutions so that each
mL contains 2 mg, and use these solutions as the test solution and the standard solution. Perform the test with
these solutions as directed under Thin-layer Chromatography. Spot 10 L each of the test solution and the
chromatography. Develop the plate with the mixture of
methylene chloride, chloroform and ethanol (10:1:1) to a
distance of about 10 cm, and air-dry the plate. Spray
evenly 0.3 % ninhydrin-ethanol on the plate: the spots
obtained from the test solution and the standard solution
is same in the Rf value.
of Bacampicillin Hydrochloride in 10 mL of water is
Purity Free ampicillin Weigh accurately about 0.1 g
of Bacampicillin Hydrochloride, transfer into a 100 mL
separator, add exactly 15 mL of ice-cold 0.05 mol/L
phosphate buffer solution, pH 7.0, then add 25 mL of icecold chlorform, shake, and abandon the chloroform layer.
Repeat the procedure twice with two 25 mL portions of
ice-cold chloroform. Centrifuge the water layer, filter the
supernatant, and use the filtrate as the test solution. Sepa-
rately, weigh accurately an amount of Ampicillin RS,

equivalent to 20 mg (potency), and dissolve in water to
make exactly 100 mL. Pipet 5 mL of this solution, add
10 mL of 0.05 mol/L phosphate buffer solution, pH 7.0
and water to make exactly 25 mL, and use this solution
as the standard solution. To exactly 10 mL each of the
test solution and the standard solution add exactly 2 mL
of sodium hydroxide TS, allow to stand for exactly 15
minutes, add exactly 2 mL of 1 mol/L hydrochloric acid
TS, exactly 10 mL of 0.3 mol/L potassium hydrogen
phthalate buffer solution, pH 4.6, and exactly 10 mL of
0.005 mol/L iodine VS, allow to stand for exactly 20 minutes without exposure to light. Titrate each of these solutions with 0.01 mol/L sodium thiosulfate VS until the
color of the solution turns to colorless. Separately, to exactly 10 mL each of the test solution and the standard solution add exactly 10 mL of 0.3 mol/L potassium hydrogen phthalate buffer solution, pH 4.6 and exactly 10 mL
of 0.005 mol/L iodine VS, and perform a blank determination with the same manner. Determine the consumed
amounts (mL) of 0.005 mol/L iodine VS, VT and VS, of
the test solution and the standard solution: the amount of
ampicillin is not more than 1.0 %.
Amount (%) of free ampicillin (C16H19N3O4S) = VT
VS
Amount(mg) of AmpicillinRS taken
100
Amount(mg) of
Bacampicillin Hydrochloride taken 20

direct titration).
Bacampicillin Hydrochloride and Bacampicillin Hydrochloride RS, dissolve each in water to make exactly
100 mL, and use these solutions as the test solution and
the standard solution. Perform the test with exactly 20
directed under the Liquid Chromatography according to
the following operating conditions, and determine the
peak areas, AT and AS , of bacampicillin of these solutions.
Amount [g (potency)] of ampicillin (C16H19N3O4S)
= Amount [g (potency) of ampicillin] of Bacampicillin
Hydrochloride RS
AT
AS
Column: A stainless steel column, about 4.6 mm in inside diameter and about 150 mm in length, packed with
KP 9 89
about 25 o C
Mobile phase: To 500 mL of diluted 2 mol/L sodium
dihydrogen phosphate TS (1 in 100), add diluted 0.05
mol/L disodium hydrogen phosphate TS (2 in 5) to adjust
the pH to 6.8. To 500 mL of this solution add 500 mL of
acetonitrile.
time of bacampicillin is about 6.5 minutes.
System suitability
the symmetry factor of the peak of bacampicillin are not
less than 10000 and not more than 2, respectively.
peak areas of bacampicillin is not more than 2.0 %.
Bacitracin
H
CH3
H2N
luble in acetone, in chloroform or in ether.

Identification To 5 mg of Bacitracin add 5 mL of pdimethylaminobenzaldehyde TS, shake and mix for one
or two minutes, then add one drop of a solution of sodium nitrite (1 in 100): a green to dark green color deveolps.
pH The pH of a solution obtained by dissolving 1 g of
Bacitracin in 10 mL of water is between 5.5 and 7.5.
Purity Heavy metalsProceed with 1.0 g of Bacitracin according to Method 1 and perform the test. Prepare
Sterility Test It meets the requirement, when Bacitracin is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Bacitracin is used in a sterile preparation. Weigh appropriate
amount of Bacitracin, dissolve in water, make the solution so that each mL contains 300 Units (potency), and
use the solution as the test solution. The amount of injection is 1.0 mL of the test solution per kg of body weight
of rabbit.
Loss on Drying Not more than 5.0 % (0.1 g, in vacuum, 60 o C , 3 hours).
H
O
L-Leu
D-Glu
Bacitracin A
Bacitracin B1
Bacitracin B2
Bacitracin B3
D-Orn
D-Phe
L-His
D-Asp
X
L-Lle
L-Lle
L-Val
L-Lle
Asp: aspartic acid

Asn: asparagines
Glu: glutamic acid
His: histidine
Ile: isoleucine
L-Lys
L-Asn
Y
L-Lle
L-Lle
L-Lle
L-Val
R
CH3
H
CH3
CH3
Leu: leucine
Lys: lysine
Orn: ornithine
Phe: phenyalanine
Bacitracin is a mixture of peptide substances having antibacterial activity including bacitracin A as the main
component produced by the growth of Bacillus subtilis
or Bacillus licheniformis.
Bacitracin contains not less than 40 Units (potency) per
mg of bacitracin A (C66H103N17O16S: 1422.69), calculated
on the dried basis.
Description Bacitracin is white to light brown powder.
Bacitracin is freely soluble in water, soluble in ethanol,
in methanol or in glacial acetic acid, and practically inso-
Assay The Cylinder-plate method (1) Culture medium Agar media for seed and base layer- Use the me1 under Microbial Assay for Antibiodium in I 2 1) (6)
tics.
(2) Test organism- Micrococcus luteus ATCC 10240.
(3) Weigh accurately about 5 mg (potency) of Bacitracin, and dissolve and dilute in 1 % phosphate buffer
solution, pH 6.0 to make the solution so that each mL
contains 2.0 and 0.5 units (potency) and use these solutions as the high concentration test solution and low concentration test solution. Separately, weigh accurately
about 5 mg (potency) of Bacitracin RS, and dissolve in
1 % phosphate buffer solution, pH 6.0 to make the solution so that each mL contains 20 units (potency), and use
this solution as the standard stock solution. Keep the
stock standard solution at not exceeding 10 C and use
stock standard solution before use, add 1 % phosphate
contains 2.0 and 0.5 units (potency), and use these solutions as the high concentration standard solution and the
low concentration standard solution, respectively. Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under Microbial Assay for Antibiotics.
dine in butanol and add butanol to make 100 mL.
(2) The diluted hydrochloric acid solution of Bacitracin Zinc (1 in 10) responds to the Qualitative Test for
zinc salt.
Bacitracin Zinc
H
CH3
H2N
pH The pH of a saturated solution of Bacitracin Zinc is

H
O
L-Leu
Bacitracin A
Bacitracin B1
Bacitracin B2
Bacitracin B3
D-Orn
D-Phe
L-His
D-Asp
X
L-Lle
L-Lle
L-Val
L-Lle
Asp: aspartic acid

Asn: asparagine
Glu: glutamic acid
His: histidine
Ile: isoleucine
D-Glu
Y
L-Lys
L-Asn
Y
L-Lle
L-Lle
L-Lle
L-Val
R
CH3
H
CH3
CH3
Leu: leucine
Lys: lysine
Orn: ornithine
Phe: phenyalanine
Bacitracin Zinc contains not less than 40 Units (potency)

per mg of bacitracin A (C66H103N17O16S: 1422.69), calculated on the dried basis. Bacitracin Zinc also contains not
less than 2.0 % and not more than 10 % of zinc (Zn:
65.41), calculated on the dried basis
Description Bacitracin Zinc is white to light yellow
powder, is odorless or a tint of odor, and has a bitter taste.
Bacitracin Zinc is slightly soluble in water or in ethanol,
very slightly soluble in ether, and practically insoluble in
chloroform.
Bacitracin Zinc is hygroscopic.
Identification (1) Weigh appropriate amount of Bacitracin Zinc, dissolve in 1 % ethylenediamine tetraaceticacid dihydrogendisodium, make the solution so that
each mL contains 6 mg, and use this solution as the test
solution. Separately, weigh appropriate amount of Bacitracin RS, dissolve in 1 % ethylenediamine tetraaceticacid dihydrogendisodium, make the solution so that each
mL contains 6 mg, and use this solution as the standard
under Thin-layer Chromatography. Spot each of the test
for thin-layer chromatography. Develop the plate with
the developing solvent which is a mixture of n-butanol,
glacial acetic acid, water, pyridine, and ethanol
(60:15:10:6:5), and air-dry the plate. Then spray evenly
ninhydrin-acetic acid TS on the plate: the spots obtained
from the test solution and the standard solution exhibit
the same Rf value. The nihydrin acetic acid TS is pepared by dissolving 1 g of ninhydrin and 1 mL of pyri-
Assay 1) bacitracin The Standard curve method

(1) Culture medium Agar media for seed and base
1 under Microbial
layer- Use the medium in I 2 1) (6)
Assay for Antibiotics. .
(2) Test organism- Use Micrococcus luteus ATCC 10240
as test organism.
(3) Weigh accurately an appropriate amount of Bacitracin Zinc, and dissolve in 0.01 mol/L hydrochloric acid
TS to make the solution so that each mL contains 100
units (potency), pipet exactly an appropriate amount of
this solution and dilute in 1 % phosphate buffer solution,
pH 6.0 to make the solution so that each mL conains 1.00
units (potency), and use this solution as the test solution.
Separately, weigh accurately an appropriate amount of
Bacitracin RS, dissolve in 0.01 mol/L hydrochloric acid
TS to make the solution so that each mL contains 100
units (potency), and use this solution as the standard
stock solution. Pipet exactly an appropriate amount of
this standard stock solution and dilute in 1 % phosphate
buffer solution, pH 6.0 to make the solutions so that each
mL contains 0.64, 0.80, 1.00, 1.25, and 1.56 units (potency) and use these solutions as the standard solutions.
Also use 1.0 unit (potency) per mL as the mid-diluted solution. Perform the test with these solutions according to
the Standard curve method (II 4) as directed under Microbial Assay for Antibiotics.
2) Zinc Weigh accurately about 0.2 g (potency) of
Bacitracin Zinc, dissolve in 0.01 mol/L hydrochloric acid
TS, and make the solution 100 mL. Pipet exactly 2 mL of
this solution and add 0.001 mol/L hydrochloric acid TS
to make 200 mL and use this solution as the test solution.
Separately, weigh accurately about 3.11 g of zinc oxide,
add 80 mL of 1 mol/L hydrochloric acid TS, heat to dissolve, allow to cool down to room temperature, and add
water to make exactly 250 mL. Pipet exactly an appropriate amount of this solution, dilute 0.001 mol/L hydrochloric acid TS to make the solutions contain 0.5, 1.5
and 2.5 g of zinc per mL, and use these solutions as the
standard solutions. Perform the test with the test solution
and the standard solutions as directed under the Atomic
Absorption Spectrophotometry. The operating wavelength is 213.8 nm. Determine absorbances and calculate
the amount of zinc according to the calibration curve method. The blank test solution is 0.001 mol/L hydrochloric
acid TS.
Amount [%] of zinc = C 100000
W (100 m )
KP 9 91
C: Amount [g /mL] of zinc in the test solution

W: Amount [mg] of Bacitracin Zinc taken
m: loss on drying (%)
Baclofen
H
HOH2CHC
Cl
NH2
and enantiomer
C10H12ClNO2: 213.66
Baclofen contains not less than 98.5% and not more than
101.0% of baclofen (C10H12ClNO2), calculated on the
anhydrous basis.
Description Baclofen is a white to pale yellowish
white, crystalline powder.
Baclofen is freely soluble in glacial acetic acid, slightly
soluble in water, very slightly soluble in methanol or in
ethanol and practically insoluble in ether.
Baclofen dissolves in dilute hydrochloric acid.
Identification (1) To 5 mL of a solution of Baclofen (1
in 1000), add 1 mL of ninhydrin TS and heat in a waterbath for 3 minutes: a blue-purple color develops.
Baclofen and Baclofen RS in 0.1 mol/L hydrochloric acid TS (1 in 2000) as directed under the Ultraviolet-visible
(3) Perform the test with Baclofen as directed under
the Flame Coloration Test (2): a green color appears.
Purity (1) ChlorideDissolve 0.5 g of Baclofen in 50
mL of glacial acetic acid and add water to make 100 mL.
To 100 mL of this solution, add 6 mL of dilute nitric acid
and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as
follows: to 0.30 mL of 0.01 mol/L hydrochloric acid VS,
add 5 mL of glacial acetic acid, 6 mL of dilute nitric acid
and water to make 50 mL (not more than 0.21%).
(2) Heavy metalsProceed with 2.0 g of Baclofen
Baclofen according to Method 3 and perform the test
(4) Related substancesDissolve 50 mg of Baclofen

in 50 mL of the mobile phase and use this solution as the
test solution. Pipet 1.0 mL and 1.5 mL of the test solution,
to each add the mobile phase to make exactly 100 mL
and use these solutions as the standard solutions (1) and
(2), respectively. Perform the test with 25 L each of the
test solution and the standard solutions (1) and (2) as directed under the Liquid Chromatography according to
the following conditions. Determine each peak height of
these solutions: each height of the peaks other than the
peak of baclofen from the test solution is not larger than
the peak height of baclofen from the standard solution
(1) and the total height of these peaks is not larger than
the peak height of baclofen from the standard solution
(2).
Mobile phase: A mixture of methanol and diluted
glacial acetic acid (1 in 900) (3 : 2).
time of baclofen is about 4 minutes.
the retention time of baclofen after the solvent peak.
System suitability
Test for required detection: Adjust the sensitivity
so that the peak height of baclofen obtained from 25 L
of the standard solution (1) is between 5 mm and 10 mm.
System performance: Dissolve 0.40 g of Baclofen
and 5 mg of methyl parahydroxybenzoate in 200 mL of
the mobile phase. To 10 mL of this solution, add the mobile phase to make 100 mL. When the procedure is run
with 25 L of this solution under the above operating
conditions, baclofen and methyl parahydroxybenzoate
above operating conditions, the relative standard deviation of the peak heights of baclofen is not more than
3.0%.
direct titration).
Assay Weigh accurately about 0.5 g of Baclofen, dissolve in 80 mL of glacial acetic acid and titrate with 0.1
mol/L perchloric acid VS until the color of the solution
changes from purple through blue to greenish blue (indicator: 2 drops of methylrosaniline chloride TS). Perform

= 21.366 mg of Cl0Hl2ClNO2
Baclofen Tablets
Baclofen Tablets contain not less than 93.0% and not
more than 107.0% of the labeled amount of baclofen
(Cl0Hl2ClNO2: 213.66).
Method of Preparation Prepare as directed under Tablets, with Baclofen.
Identification (1) To a portion of powdered Baclofen
Tablets, equivalent to 10 mg of Baclofen according to the
labeled amount, add 10 mL of water, shake well and filter.
To 5 mL of the filtrate, add 1 mL of ninhydrin TS and
proceed as directed in the Identification (1) under Baclofen.
(2) To a portion of powdered Baclofen Tablets,
equivalent to 25 mg of Baclofen according to the labeled
amount, add 50 mL of 0.1 mol/L hydrochloric acid TS,
shake for 15 minutes and filter. Determine the absorption
spectrum of the filtrate as directed under the Ultravioletvisible Spectrophotometry: it exhibits maxima between
257 nm and 261 nm, between 264 nm and 268 nm and
between 272 nm and 276 nm.
(3) To a portion of powdered Baclofen Tablets,
equivalent to 10 mg of Baclofen according to the labeled
amount, add 2 mL of a mixture of methanol and glacial
acetic acid (4 : 1), shake well, centrifuge and use the supernatant liquid as the test solution. Separately, dissolve
10 mg of Baclofen RS in 2 mL of a mixture of methanol
and glacial acetic acid (4 : 1) and use this solution as the
and the standard solution as directed under the Thin-layer
Chromatography. Spot 20 L each of the test solution
and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of n-butanol, water and glacial acetic acid (4 : 1 : 1) to a distance of about 10 cm
(main wavelength: 254 nm): the spot from the test solution and that from the standard solution show the same
Rf value.
Dissolution Test Perform the test with 1 tablet of Baclofen Tablets at 50 revolutions per minute according to
water as the dissolution solution. Take 20 mL or more of
the dissolve solution 45 minutes after starting the test and
filter. Discard the first 10 mL of the filtrate, pipet V mL
of the subsequent, filtrate, add water to make exactly V'
mL so that each mL contains about 10 g of baclofen

(Cl0Hl2ClNO2) according to the labeled amount and use
this solution as the test solution. Separately, weigh accurately about 10 mg of Baclofen RS (separately determined the water content), dissolve in water to make exactly 100 mL, then pipet 10 mL of this solution, add water to make exactly 100 mL and use this solution as the
standard solution. Determine the absorbances, AT and
AS , of the test solution and the standard solution at 220

nm, respectively, as directed under the Ultraviolet-visible
Spectrophotometry.
The dissolution rate (%) of Baclofen Tablets in 45 minutes is not less than 70%.
of baclofen (Cl0Hl2ClNO2) = W S
AT V ' 1
50
AS V C
WS : Amount (mg) of Baclofen RS.

C: Labeled amount (mg) of baclofen (Cl0Hl2ClNO2)
in 1 tablet.
Baclofen Tablets. Weigh accurately a portion of the
powder, equivalent to about 50 mg of baclofen
(Cl0Hl2ClNO2), add 130 mL of 0.1 mol/L hydrochloric
acid TS, shake for 10 minutes, add 0.1 mol/L hydrochloric acid TS to make exactly 200 mL and centrifuge. Pipet
10 mL of the supernatant liquid, add 2 drops of phenolphthalein TS, neutralize with dilute sodium hydroxide
TS, add water to make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately
about 0.25 g of Baclofen RS (separately determined the
water content) and dissolve in 0.1 mol/L hydrochloric acid TS to make exactly 100 mL. Pipet 10 mL of this solution and add 0.1 mol/L hydrochloric acid TS to make exactly 100 mL. Pipet 10 mL of this solution, add 2 drops
of phenolphthalein TS, neutralize with dilute sodium hydroxide TS, add water to make exactly 50 mL and use
this solution as the standard solution. Pipet 2 mL each of
the test solution and the standard solution, to each add 4
mL of ninhydrin-stannous chloride TS, shake, heat in a
water-bath for 20 minutes and shake at once vigorously
for 2 minutes. After cooling, to each solution, add a mixture of water and n-propanol (1 : 1) to make exactly 25
mL. Determine the absorbances, AT and AS , of the
570 nm as directed under the Ultraviolet-visible Spectrophotometry, using a blank prepared with 2 mL of water
in the same manner.
Amount (mg) of baclofen (Cl0Hl2ClNO2)
= amount (mg) of Baclofen RS,
KP 9 93
(2) Related substancesDissolve 5.0 mg of Bambuterol Hydrochloride in the mobile phase, dilute to 10.0
mL with the mobile phase, and use this solution as the
test solution. Separately, dissolve 1.0 mg of Formoterol
Packaging and Storage Preserve in well-closed conFumarate Dihydrate RS in the mobile phase, dilute to 10
tainers.
mL with the mobile phase. Mix 0.8 mL of this solution
with 0.4 mL of the test solution, dilute to 100 mL with
the mobile phase, and use this solution as the standard
Bambuterol Hydrochloride
solution (1). Dilute 1.0 mL of the test solution with the
mobile phase to 50 mL. Dilute 2.0 ml of the solution to
CH3
20 mL with the mobile phase, and use this solution as the
H
OH
H
standard solution (2). Use the mobile phase as the blank
N
CH3
N
O
H 3C
solution. Perform the test with 20 L each of the blank
H 3C
CH3
solution, the test solution, and the standard solutions as
O
HCl
CH3
the following conditions. The area of any peak, other
N
O
than from the principal peak, from the test solution is not
H 3C
greater than the area of the principal peak from the stanO
dard solution (2) (not more than 0.2%); the sum of the
and enantiomer
areas of all the peaks, other than from the principal peak,
is not greater than 3 times the area of the principal peak
C18H29N3O5,HCl : 403.90 from the standard solution (2) (not more than 0.6%). Disregard any peak obtained with the blank solution and any
Bambuterol Hydrochloride contains not less than 98.5%
peak with an area less than 0.25 times the area of the
and not more than 101.5% of bambuterol hydrochloride
principal peak obtained with the standard solution (2).
(C18H29N3O5,HCl), calculated on the anhydrous basis.
Description Bambuterol Hydrochloride is a white,
Detector: An ultraviolet absorption photometer (wacrystalline powder.
velength: 214 nm)
Bambuterol Hydrochloride is freely soluble in water, and
Column: A stainless steel column about 4.6 mm insoluble in ethanol.
side diameter and 15 cm in length, packed with baseBambuterol Hydrochloride shows polymorphism.
deactivated octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Identification (1) Determine the infrared absorption
Mobile phase: Dissolve 1.3 g of sodium octanesulspectra of Bambuterol Hydrochloride and Bambuterol
phonate in 430 mL of a mixture of methanol and acetoniHydrochloride RS as directed in the potassium bromide
trile (75:25). Mix this solution with 570 mL of phosphate
disk method under the Infrared Spectrophotometry: both
buffer solution.
Flow rate: 1.5 mL/min.
same wavenumbers. If any difference appears between
System suitability
the spectra, dissolve Bambuterol Hydrochloride and
System performance: Adjust the sensitivity of the
Bambuterol Hydrochloride RS in a mixture of acetone
system so that the height of the principal peak from the
and water (6 : 1), cool in ice to precipitate, then dry both
standard solution (2) is about 50% of the full scale of the
precipitates in vacuum at 50 C to constant weight, and
recorder. When the procedure is run with 20 L of the
repeat the test with precipitates.
standard solution (1), the retention times for formoterol
(2) The solution of Bambuterol Hydrochloride in waand bambuterol are about 7 and 9 minutes, respectively,
ter (1 in 50) responds to the Qualitative Tests for chlowith the resolution between the peaks of bambuterol and
ride (2nd method).
formoterol being not less than 5.0.
Time span of measurement: 1.5 times the retention
time of bambuterol.
D : Between 0.10 and
+0.01 (0.4 g calculated on the anhydrous basis, water,
Phosphate buffer solutionDissolve 6.90 g of so20 mL, 100 mm).
dium dihydrogen phosphate monohydrate in water to
make 1000 mL, and adjust the pH to 3.0 with 5% phosPurity (1) Acidity or alkalinity Dissolve 4.0 g of
phoric acid.
Bambuterol Hydrochloride in water to make exactly 20
mL. To 10 mL of the solution, add 0.2 mL of methyl red
TS and 0.2 mL of 0.01 mol/L hydrochloric acid. The sodirect titration).
lution is red. When 0.4 mL of 0.01 mol/L sodium hydroxide is added, the solution becomes yellow.
calculated on the anhydrous basis
AT
AS
Assay Dissolve 0.320 g of Bambuterol Hydrochloride,

accurately weighed, in 50 mL of ethanol, add 5 mL of
0.01 mol/L hydrochloric acid, and titrate with 0.1 mol/L
sodium hydroxide VS (potentiometric titration, Endpoint
Detection Method in Titrimetry). Read the volume added
between the two points of inflexion. Perform a blank determination and make any necessary correction.
= 40.39 mg of C18H30ClN3O5
Bamethan Sulfate
OH
HO
H2SO 4
CCH 2NHCH 2CH2CH 2CH3

2
and enantiomer
(C12H19NO2)2H2SO4: 516.65
Bamethan Sulfate, when dried, contains not less than
99.0% and not more than 101.0% of bamethan sulfate[(C12H19NO2)2 H2SO4].
Description Bamethan Sulfate is a white crystal or
Bamethan Sulfate is freely soluble in water or in glacial
acetic acid, soluble in methanol, slightly soluble in ethanol and practically insoluble in ether..
Melting point About 169 C (with decomposition)
Identification (1) To 1 mL of a solution of Bamethan
Sulfate (1 in 1000), add 5 mL of a solution of pnitrobenzene-diazonium ftuoroborate (1 in 2000) and 10
mL of boric acid-potassium chloride-sodium hydroxide
buffer solution, pH 9.2: an orange-red color is observed.
(2) Determine the absorption spectra of the solutions
of Bamethan Sulfate and Bamethan Sulfate RS in 0.01
mol/L hydrochloric acid TS (1 in 10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavelengths.
(3) Determine the infrared spectra of Bamethan Sulfate and Bamethan Sulfate RS, previously dried, as directed in the potassium bromide disk method under the
(4) A solution of Bamethan Sulfate (1 in 100) responds to the Qualitative Tests for sulfate
pH Dissolve 1.0 g of Bamethan Sulfate in 10 mL of
water: The pH of this solution is between 4.0 and 5.5.

1.0 g of Bamethan Sulfate in 20 mL of water: the solution is clear and has no more color than the following
control solution.
Control solutionTo 1.5 mL of Color Matching Fluid O, add diluted hydrochloric acid (1 in 40) to make 200
mL.
(2) ChloridePerform the test with 3.5 g of Bamethan Sulfate. Prepare the control solution with 0.25 mL
of 0.01 mol/L hydrochloric acid VS (not more than
0.002%).
(3) Heavy metalsProceed with 2.0 g of Bamethan
Sulfate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Bamethan Sulfate according to Method 3 and perform
(5) Related substancesDissolve 0.10 g of Bamethan Sulfate in 2 mL of methanol and use this solution as
the test solution. Pipet 1 mL of the test solution, add methanol to make exactly 100 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer Chromatography. Spot 2 L each of the test solution and the standard solution on a plate of silica gel for
thin-layer chromatography. Develop the plate with a
mixture of chloroform and methanol (7 : 2) in a developing vessel saturated with ammonia vapor to a distance of
about 12 cm and air-dry the plate. Spray evenly Dragendorffs TS for spraying on the plate, air-dry for 15 minutes, spray Dragendorffs TS for spraying again, then,
after 1 minute, spray evenly a solution of sodium nitrite
(1 in 20) and immediately put a glass plate on the plate.
Examine the plate after 30 minutes: the spots other than
the principal spot from the test solution are not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately about 0.75 g of Bamethan Sulfate, previously dried, dissolve in 80 mL of glacial acetic
acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 51.67 mg of (C12H19NO2)2H2SO4
KP 9 95
Barbital
O
H
N
CH3CH2
NH
CH3CH2
O
C8H12N2O3: 184.19
Barbital, when dried, contains not less than 99.0% and
not more than 101.0% of barbital (C8H12N2O3).
Description Barbital is a colorless or white crystal or
crystalline powder, is odorless and has a slightly bitter
taste.
Barbital is freely soluble in acetone or in pyridine, soluble in ethanol, sparingly soluble in ether and slightly
soluble in water or in chloroform.
Barbital dissolve in sodium hydroxide TS and in ammonia TS.
pHIts saturated solution is between 5.0 and 6.0.
Identification (1) Boil 0.2 g of Barbital with 10 mL of
sodium hydroxide TS: the gas evolved changes moistened red litmus paper to blue.
(2) Dissolve 50 mg of Barbital in 5 mL of diluted pyridine (1 in 10), add 0.3 mL of cupric sulfate TS, shake
and allow to stand for 5 minutes: a red-purple precipitate
is formed. Shake the mixture with 5 mL of chloroform: a
red-purple color develops in the chloroform layer. Separately, dissolve 50 mg of Barbital in 2 to 3 drops of ammonia-ammonium chloride buffer solution, pH 10.7 and
5 mL of diluted pyridine (1 in 10). Add 5 mL of chloroform and 0.3 mL of cupric sulfate TS to the solution: a
red-purple precipitate is produced in the aqueous layer.
The red-purple precipitate is not dissolve in the chloroform by shaking.
(3) To 0.4 g of Barbital, add 0.1 g of anhydrous sodium carbonate and 4 mL of water, shake and add a solution of 0.3 g of p-nitrobenzyl chloride in 7 mL of ethanol.
Heat the mixture in a water-bath under a reflux condenser for 30 minutes and allow to stand for 1 hour. Collect
the separated crystals, wash with 7 mL of sodium hydroxide TS and a small amount of water, recrystalize
from a mixture of ethanol and chloroform (1 : 1) and dry
at 105 C for 30 minutes: the crystals melt between 192
C and 196 C.
Melting Point
Between 189 C and 192 C

0.5 g of Barbital in 5 mL of sodium hydroxide TS: the
(2) ChlorideDissolve 0.30 g of Barbital in 20 mL
of acetone and add 6 mL of dilute nitric acid and water to
make 50 mL. Perform the test using this solution as the
test solution. Prepare the control solution as follows: take

0.30 mL of 0.01 mol/L hydrochloric acid VS, 20 mL of
acetone and 6 mL of dilute nitric acid and add water to
(3) SulfateDissolve 0.40 g of Barbital in 20 mL of
acetone and add 1 mL of dilute hydrochloric acid and
water to make 50 mL. Perform the test using this solution
as the test solution. Prepare the control solution as follows: take 0.40 mL of 0.005 mol/L sulfuric acid VS, 20
mL of acetone and 1 mL of dilute hydrochloric acid and
add water to make 50 mL (not more than 0.048%).
(4) Heavy metalsProceed with 1.0 g of Barbital
test with 0.5 g of Barbital. The solution has not more
hours).
Assay Weigh accurately 0.4 g of Barbital, previously
dried and dissolve in 5 mL of ethanol and 50 mL of chloroform. Titrate with 0.1 mol/L potassium hydroxideethanol VS until the color of the solution changes from
yellow through pale blue to purple (indicator: 1 mL of
alizarin yellow GG-thymolphthalein TS). Perform a
= 18.419 mg of C8H12N2O3
Barium Sulfate
BaSO4: 233.39
Description Barium Sulfate is a white powder, is odorless and tasteless.
Barium Sulfate is practically insoluble in water, in ethanol or in ether.
Barium Sulfate does not dissolve in hydrochloric acid, in
nitric acid or in sodium hydroxide TS.
Identification (1) Mix 0.5 g of Barium Sulfate with 2
g each of anhydrous sodium carbonate and anhydrous
potassium carbonate in a crucible, heat the mixture until
fusion is complete, treat the cooled mass with hot water
and filter. The filtrate, acidified with hydrochloric acid,
(2) Wash the hot water-insoluble residue obtained in
(1) with water, dissolve in 2 mL of acetic acid and filter,
if necessary: the solution responds to the Qualitative
Tests for barium salt.
Purity (1) Acidity or alkalinityAgitate 1.0 g of Barium Sulfate with 20 mL of water for 5 minutes: the solution is neutral.
(2) PhosphateBoil 1.0 g of Barium Sulfate with 3
mL of nitric acid and 5 mL of water for 5 minutes, cool
and add water to restore the original volume. Filter
through a filter paper, previously washed with dilute nitric acid, to the filtrate, add an equal volume of ammonium molybdate TS and allow to stand between 50 C
and 60 C for 1 hour: no yellow precipitate is produced.
(3) SulfidePlace 10 g of Barium Sulfate in a 250
mL Erlenmeyer flask, add 10 mL of dilute hydrochloric
acid and water to make 100 mL and boil for 10 minutes:
the gas evolved does not darken moistened lead acetate
paper.
(4) Heavy metalsBoil 5.0 g of Barium Sulfate
with 2.5 mL of glacial acetic acid and 50 mL of water for
10 minutes, cool, add 0.5 mL of ammonia TS and water
to make 100 mL and filter. Perform the test with 50 mL
of this filtrate. Prepare the control solution with 2.5 mL
of standard lead solution, 1.25 mL of glacial acetic acid,
0.25 mL of ammonia TS and water to make 50 mL (not
more than 10 ppm).
Barium Sulfate according to Method 1 and perform the
(6) Hydrochloric acid-soluble substances and soluble barium saltsCool the solution obtained in (3),
add water to make 100 mL and filter. Evaporate 50 mL of
the filtrate on a water-bath to dryness, add 2 drops of hydrochloric acid and 10 mL of warm water, filter through
filter paper for assay and wash with 10 mL of warm water. Evaporate the combined filtrate and washings on a
water-bath to dryness and dry the residue at 105 C for 1
hour: the residue weighs not more than 15 mg. Shake the
residue, if any, with 10 mL of water and filter. To the filtrate, add 0.5 mL of dilute sulfuric acid and allow to
stand for 30 minutes: no turbidity is produced.
Beclomethasone Dipropionate
O
O
C
H
H3C
HO
CH2O
O
O
CH2CH3
CH2CH3
H3C
CH3
Cl
C28H37ClO7 : 521.04
Beclomethasone Dipropionate, when dried, contains not

less than 97.0% and not more than 103.0% of beclomethasone dipropionate (C28H37ClO7).
Description Beclomethasone Dipropionate is a white
to pale yellow powder and is odorless.
Beclomethasone Dipropionate is freely soluble in chloroform, soluble in methanol, sparingly soluble in ethanol or
in dioxane, slightly soluble in ether and practically insoluble in water.
Melting point About 208 C (with decomposition).
Identification (1) Dissolve 2 mg of Beclomethasone
Dipropionate in 2 mL of sulfuric acid: initially a yellowish color develops and gradually changes through
orange to dark red-brown. To this solution, add carefully
10 mL of water: the color changes to bluish green and a
flocculent precipitate is formed.
(2) Dissolve 10 mg of Beclomethasone Dipropionate
in 1 mL of methanol, add 1 mL of Fehlings TS and heat:
a red to red-brown precipitate is formed.
(3) Prepare the test solution with 20 mg of Beclomethasone Dipropionate as directed under the Oxygen Flask
Combustion Method, using a mixture of 1 mL of sodium
hydroxide TS and 20 mL of water as an absorbing liquid:
the test solution responds to the Qualitative Tests for
chloride.
(4) Determine the infrared spectra of Beclomethasone Dipropionate and Beclomethasone Dipropionate RS,
disk method under the Infrared Spectro-photometry: both
same wavenumbers. If any difference appears between
the spectra, dissolve Beclomethasone Dipropionate and
Beclomethasone Dipropionate RS in ethanol, then evaporate the ethanol to dryness and repeat the test with the residues.
D : Between +88 and
+94 (after drying, 0.1 g, dioxane, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 0.5 g of Beclomethasone Dipropionate according to Method 2 and
mL of standard lead solution (not more than 30 ppm)
(2) Related substancesDissolve 20 mg of Beclomethasone Dipropionate in 5 mL of a mixture of chloroform and methanol (9 : 1) and use this solution as the test
solution. Pipet 1 mL of the test solution, add a mixture of
chloroform and methanol (9 : 1) to make exactly 50 mL
the test with the test solution and the standard solutions
as directed under the Thin-layer Chromatography. Spot 5
L each of the test solution and the standard solution on
a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1,2-dichloroethane, methanol and water (475 : 25 : 1) to a distance of about 15
KP 9 97
cm and air-dry the plate. Spray evenly alkaline blue tetrazolium TS on the plate: the spots other than the principal spot from the test solution are not more intense than
hours).
Benserazide Hydrochloride
HO
H
HOCH2C
NHNHCH2
OH
OH
HCl
NH2

Asssy Weigh accurately, about 20 mg each of Beclomethasone Dipropionate and Beclomethasone Dipropionate RS, previously dried and dissolve each in methanol
to make exactly 50 mL. Pipet 10 mL each of the test solution and the standard solution, add exactly 10 mL of
the internal standard solution and methanol to make 50
mL and use these solutions as the test solution and the
standard solution, respectively. Perform the test with 20
and QS , of the peak area of Beclomethasone Dipropionate to that of the internal standard, for the test solution
and the standard solution, respectively.
Amount (mg) of C28H37ClO7 = amount (mg) of Beclomethasone Dipropionate RS
QT
QS
Internal standard solutionA solution of testosterone propionate in methanol (1 in 4000).

Mobile phase: A mixture of acetonitrile and water (3 :
2).
time of Beclomethasone Dipropionate is about 6 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, beclomethasone dipropionate and the
internal standard are eluted in this order with the resolution between their peaks being not less than 8.
above operating conditions, the relative standard deviation of the ratios of the peak area of beclomethasone dipropionate to that of the internal standard is not more
than 1.0 %.
and enantiomer
C10H15N3O5HCl: 293.70
Benserazide Hydrochloride contains not less than 98.0%
and not more than 101.0% of benserazide hydrochloride
Description Benserazide Hydrochloride is a white to
grayish white, crystalline powder.
Benserazide Hydrochloride is freely soluble in water or
in formic acid, soluble in methanol, very slightly soluble
in ethanol and practically insoluble in ether.
Benserazide Hydrochloride is hygroscopic.
Benserazide Hydrochloride is gradually affected by light.
A solution of Benserazide Hydrochloride (1 in 100)
shows no optical rotation.
pHDissolve 1.0 g of a solution of Benserazide Hydrochloride in 100 mL of water: the pH of this solution is
the solutions of Benserazide Hydrochloride and Benserazide Hydrochloride RS in 0.1 mol/L hydrochloric acid
TS (1 in 10000) as directed under the Ultraviolet-visible
(2) Determine the infrared spectra of Benserazide
Hydrochloride and Benserazide Hydrochloride RS as directed in the potassium bromide disk method under the
Infrared Spectrophotometry,: both spectra exhibit similar
(3) To 10 mL of a solution of Benserazide Hydrochloride (1 in 30), add silver nitrate TS: a white precipitate
is produced. To a portion of this precipitate, add dilute
nitric acid: the precipitate does not dissolve.
g of Benserazide Hydrochloride in 10 mL of water and
perform the test with this solution as directed under the
Ultraviolet-visible Spectrophotometry: the absorbance of
this solution at 430 nm is not more than 0.10.
(2) Heavy metalsProceed with 1.0 g of Benserazide Hydrochloride in according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
(3) Related substancesPerform the test without
exposure to daylight, using light-resistant vessels. Dissolve 0.25 g of Benserazide Hydrochloride in 10 mL of
methanol and use this solution as the test solution. Pipet
1 mL and 3 mL of the test solution, add methanol to
make exactly 200 mL and use these solutions as the standard solutions (1) and (2), respectively. Perform the test
with the test solution and the standard solutions (1) and
(2) as directed under the Thin-layer Chromatography.
Spot 2 L each of the test solution and the standard solutions (1) and (2) on a plate of cellulose for thin-layer
chromato-graphy. Develop the plate with a solution of
formic acid in sodium chloride TS (1 in 1000) to a distance of about 10 cm and air-dry the plate. Spray evenly
sodium carbonate TS, air-dry and then spray evenly Folins TS on the plate: the spots other than the principal
spot from the test solution are not more intense than the
spot from the standard solution (2) and the numbers of
the spots which are more intense than the spot from the
standard solution (1) are not more than 2.
direct titration). Use a solution of salicylic acid in methanol for Karl Fischer Method (3 in 20) instead of methanol for Karl Fischer Method.
Assay Weigh accurately 0.3 g of Benserazide Hydrochloride, dissolve in 5 mL of formic acid, add 50 mL of
glacial acetic acid and titrate immediately with 0.1 mol/L
perchloric acid VS (potentiometric titration, Endpoint
Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 29.370 mg of C10H15N3O5HCl
tight containers.
Benzalkonium Chloride
Benzalkonium Chloride is represented by the formula
[C6H5CH2N(CH3)2R]Cl, in which R extends from C8H17
to C18H37, with C12H25 and C14H29 comprising the major
portion.
Benzalkonium Chloride contains not less than 95.0% and
not more than 105.0% of benzalkonium chloride
(C22H40ClN: 354.01) calculated on the anhydrous basis.
Description Benzalkonium Chloride is a white to yellowish white powder, colorless to pale yellow, gelatinous
pieces or jelly-like fluid or mass. Benzalkonium Chloride
has a characteristic odor.
Benzalkonium Chloride is very soluble in water or in
A solution of Benzalkonium Chloride foams strongly
when shaken.
Identification (1) Dissolve 0.2 g of Benzalkonium
Chloride in 1 mL of sulfuric acid, add 0.1 g of sodium ni-
trate and heat for 5 minutes in a water-bath. After cooling,

add 10 mL of water and 0.5 g of zinc powder, heat for 5
minutes, cool and filter: the filtrate responds to the Qualitative Tests for primary aromatic amines. The color of
the solution is red.
(2) To 2 mL of a solution of Benzalkonium Chloride
(1 in 1000), add a mixture of 0.2 mL of a solution of
bromophenol blue (1 in 2000) and 0.5 mL of sodium hydroxide TS: a blue color is observed. Add 4 mL of chloroform to this solution and shake vigorously: the blue
color shifts to the chloroform layer. Collect the chloroform layer and add dropwise, with stirring, a solution of
sodium lauryl sulfate (1 in 1000): the chloroform layer
turns colorless.
of Benzalkonium Chloride and Benzalkonium Chloride
RS in 0.1 mol/L hydrochloric acid VS (1 in 2000) as directed under the Ultraviolet-visible Spectrophotometry:
both spectra exhibit similar intensitiesof absorption at the
same wavenumbers.
(1 in 100), add 2 mL of ethanol, 0.5 mL of dilute nitric
acid and 1 mL of silver nitrate TS: a white precipitate is
produced. This precipitate does not dissolve on the addition of dilute nitric acid, but dissolves on the addition of
ammonia TS.
g of Benzalkonium Chloride in 10 mL of water: the solution is clear and colorless, or pale yellow.
(2) Petroleum ether-soluble substancesTo 3.0 g
of Benzalkonium Chloride, add water to make 50 mL,
then add 50 mL of dehydrated ethanol and 5 mL of 0.5
mol/L sodium hydroxide TS and extract with three 50
mL volumes of petroleum ether. Combine the petroleum
ether extracts and wash with three 50 mL volumes of dilute ethanol. After shaking well with 10 g of anhydrous
sodium sulfate, filter through a dry filter paper and wash
the filter paper with two 10 mL volumes of petroleum
ether. Evaporate the petroleum ether on a water-bath by
heating and dry the residue at 105 C for 1 hour: the residue is not more than 1.0%.
Assay Weigh accurately 0.15 g of Benzalkonium Chloride and dissolve in 75 mL of water. Adjust the pH between 2.6 and 3.4 by adding drop-wise diluted dilute hydrochloric acid (1 in 2), add 1 drop of methylorange TS
and titrate with 0.02 mol/L sodium tetraphenylboron VS
until the color of the solution becomes red.
Each mL of 0.02 mol/L sodium tetraphenylboron VS
= 7.080 mg of C22H40ClN
KP 9 99
Benzalkonium Chloride Concentrated Solution 50

Benzalkonium Chloride Concentrated Solution 50 is an
aqueous solution, presented as [C6H5CH2N(CH3)2R] Cl,
where R ranges from C8H17 to C18H37 and mainly consisting of C12H25 and C14H29.
Benzalkonium Chloride Concentrated Solution 50 contains not less than 50.0% and not more than 55.0% of
benzalkonium chloride (C22H40ClN: 354.01).
Description Benzalkonium Chloride Concentrated Solution 50 is a clear, colorless to pale yellow liquid or jelly-like fluid and has a characteristic odor.
Benzalkonium Chloride Concentrated Solution 50 is very
soluble in water or in ethanol and practically insoluble in
ether.
A solution prepared by adding water to Benzalkonium
Chloride Concentrated Solution 50 vigorously foams
when shaken.
Identification (1) Dissolve 0.4 g of Benzalkonium
Chloride Concentrated Solution 50 in 1 mL of sulfuric
acid, add 0.1 g of sodium nitrate, and heat for 5 minutes
on a water bath. After cooling, add 10 mL of water and
0.5 g of zinc powder, heat for 5 minutes, cool, and filter:
the filtrate responds to the Qualitative Tests for primary
aromatic amines. The color of the solution is red.
Concentrated Solution 50 (1 in 500), add a mixture of 0.2
mL of a solution of bromophenol blue (1 in 2000) and
0.5 mL of sodium hydroxide TS: a blue color develops.
Add 4 mL of chloroform to this solution, and shake vigorously: the blue cool shifts to the chloroform layer. Collect the chloroform layer, and add dropwise, with stirring,
a solution of sodium lauryl sulfate (1 in 1000): the chloroform layer turns colorless.
of Benzalkonium Chloride Concentrated Solution 50 and
Benzalkonium Chloride Concentrated Solution 50 RS in
0.1 mol/L hydrochloric acid VS (1 in 1000) as directed
under the Ultraviolet-visible Spectrophotometry: both
same wavelengths.
Concentrated Solution 50 (1 in 50), add 2 mL of ethanol,
0.5 mL of dilute nitric acid and 1 mL of silver nitrate TS;
a white precipitate is produced. This precipitate does not
dissolve on the addition of dilute nitric acid, but dissolves on the addition of ammonia TS.
2.0 g of Benzalkonium Chloride Concentrated Solution
50 in 10 mL of water: the solution is clear and colorless
to pale yellow.
(2) Petroleum ether-soluble substancesTo 6.0 g of
Benzalkonium Chloride Concentrated Solution 50, add

water to make 50 mL, then add 50 mL of dehydrated
ethanol and 5 mL of 0.5 mol/L sodium hydroxide TS and
extract with three 50 mL volumes of petroleum ether.
Combine the petroleum ether extracts and wash with
three 50 mL volumes of dilute ethanol. After shaking
well with 10 g of anhydrous sodium sulfate, filter
through a dry filter paper and wash the filter paper with
two 10 mL volumes of petroleum ether. Evaporate the
petroleum ether on a water-bath by heating and dry the
residue at 105 C for 1 hour: the residue is not more than
1.0%.
Assay Weigh accurately 0.30 g of Benzalkonium Chloride Concentrated Solution 50 and dissolve in 75 mL of
water. Adjust the pH between 2.6 and 3.4 by adding
drop-wise diluted dilute hydrochloric acid (1 in 2), add 1
drop of methylorange TS and titrate with 0.02 mol/L sodium tetraphenylboron VS until the color of the solution
becomes red.
= 7.080 mg of C22H40ClN
Benzalkonium Chloride Solution

Benzalkonium Chloride Solution is an aqueous solution
containing not more than 50.0 w/v% of Benzalkonium
Chloride.
Benzalkonium Chloride Solution contains not less than
of benzalkonium chloride (C22H40ClN: 354.01).
Method of Preparation Dissolve Benzalkonium Chloride in Water or Purified Water. Benzalkonium Chloride
Solution is also prepared by diluting Benzalkonium
Chloride Concentrated Solution 50 with Water or Purified Water.
Description Benzalkonium Chloride Solution is a clear,
colorless to pale yellow liquid, and has a characteristic
odor.
Benzalkonium Chloride Solution foams strongly on
shaking.
Identification (1) Evaporate a volume of Benzalkonium Chloride Solution, equivalent to 0.2 g of Benzalkonium Chloride according to the labeled amount, on a water-bath to dryness and proceed with the residue as directed in the Identification (1) under Benzalkonium
Chloride.
(2) To a volume of Benzalkonium Chloride Solution,
equivalent to 10 mg of Benozalkonium Chloride accord-

ing to the labeled amount, add water to make 10 mL.
Proceed with 2 mL of this solution as directed in the
Identification (2) under Benzalkonium Chloride.
equivalent to 1 g of Benozalkonium Chloride according
to the labeled amount, add water or concentrate on a water-bath, if necessary, to make 10 mL. To 1 mL of this solution, add 0.1 mol/L hydrochloric acid VS to make 200
mL and proceed as directed in the Identification (3) under Benzalkonium Chloride.
equivalent to 0.1 g of Benozalkonium Chloride according to the labeled amount, add water or concentrate on a
water-bath, if necessary, to make 10 mL. Proceed with 1
mL of this solution as directed in the Identification (4)
under Benzalkonium Chloride.
Assay Pipet a volume of Benzalkonium Chloride Solution, equivalent to about 0.15 g of benzalkonium chloride
(C22H40ClN), dilute with water to make 75 mL, if necessary and proceed as directed in the Assay under Benzalkonium Chloride.
= 7.080 mg of C22H40ClN
Benzathine Penicillin G
Hydrate
O
HO
H
Benzathine Penicillin G Weigh accurately about 50

mg of Benzathine Penicillin G Hydrate, dissolve in methanol and make exactly 100 mL. Determine absorbance
of this solution at 263 nm with methanol as control solu-
S
H
.
N
H
Identification (1) Dissolve 0.1 g of Benzathine Penicillin G Hydrate in 1 mL of 1 mol/L sodium hydroxide,
shake for 2 minutes, add 2 mL of ether, shake for one
minute, stand, take ether layer and dry. To resulting residues add 2 mL of glacial acetic acid and dissolve. To this
solution add 1mL of potassium dichromate TS: a yellow
precipitate develops.
(2) Dissolve 0.1 g of Benzathine Penicillin G Hydrate
in 2 mL of 1 mol/L sodium hydroxide, shake for 2 minutes, extract with 3 mL of ether twice, and take ether
layers and dry. To resulting residues add 1 mL of 50 %
ethanol and 5 mL of picric acid TS, heat for 5 minutes at
90 C and cool slowly. To the produced precipitate add
50 % ethanol containing small amount of picric acid, recrystallize, and determine melting point: metlting point is
about 214 C.
of Benzathine Penicillin G Hydrate and Benzathine Penicillin G Hydrate RS in methanol (1 in 200), as directed
under Ultraviolet-visible Spectrophotometry, both spectra exhibit similar intensities of absorption at the same
wavelengths.
(4) Determine the infrared spectra of Benzathine Penicillin G Hydrate and Benzathine Penicillin G Hydrate
RS, as directed in the potassium bromide disk method
under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
1%
tion, and obtain E1 cm .
CH3
CH3
N
H
water.
H
N
Amount [%] of Benzathine Penicillin G

4H2O
(C16H18N2O4S)2 C16H20N24H2O: 981.19

Benzathine Penicillin G Hydrate is the N, Ndibenzylethylenediamine salt of a penicillin compound
having antibacterial activity produced by the growth of
Penicillium species.
Benzathine Penicillin G Hydrate contains not less than
1050 Units (potency) per mg of penicillin G sodium
(C16H17N2NaO4S: 356.37), and benzathine penicillin G is
not less than 85.0 %, calculated on the dried basis.
Description Benzathine Penicillin G Hydrate is a
white crystalline powder.
Benzathine Penicillin G Hydrate is sparingly soluble
in dimethylformamide or in formamide, slightly soluble
in methanol or in ethanol, and very slightly soluble in
%
= E11cm
100
7
pH The pH of a saturated solution of Benzathine Penicillin G Hydrate is between 5.0 and 7.5.
Sterility Test It meets the requirement, when Benzathine Penicillin G Hydrate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Benzathine Penicillin G Hydrate is used in a sterile preparation.
Weigh appropriate amount of Benzathine Penicillin G
Hydrate, dissolve in saline injection solution, make a
suspension so that each mL contains 2000 Units (potency), and use the suspension as the test solution. The
amount of injection is 1.0 mL of the test solution per kg
of body weight of rabbit.
direct titration).
KP 9 101
Assay Weigh accurately an appropriate amount of

Benzathine Penicillin G Hydrate, and dissolve in 1 mol/L
sodium hydroxide TS to make the solution containing
2000 units (potency) per mL, and use this solution as the
test solution. Pipet exactly 2 mL of the test solution,
transfer into a separator, allow to stand for 15 minutes,
add exactly 2.0 mL of diluted hydrochloric acid (1 in 10)
and 10 mL of 0.01 mol/L iodine VS and allow to stand
for 15 minutes, if necessary, add about 5 mL of carbon
tetrachloride and shake. Titrate this solution with 0.01
mol/L sodium thiosulfate VS until the color of the solution changes to colorless. When carbon tetrachloride is
added, titrate until the color of the layer of carbon tetrachloride changes to colorless. If necessary, use 0.2 mL
to 0.5 mL of starch solution TS as indicator solution.
Separately, weigh accurately an appropriate amount of
Penicillin G Sodium RS, dissolve in 1 % phosphate buffer, pH 6.0 and make the solution contain 2000 units (potency) per mL, and use this solution as the standard solution. Pipet exactly 2 mL of the standard solution, transfer
into a separator, add 2.0 mL of 1 mol/L sodium hydroxide TS, allow to stand for 15 minutes, and titrate as the
above. Separately, weigh accurately an appropriate
amount of Benzathine Penicillin G Hydrate, suspend in
1 % phosphate buffer, pH 6.0 and make the suspension
contain 2000 units (potency) per mL. Pipet exactly 2 mL
each of this suspension and the standard solution, transfer each into separators, add exactly 10 mL of 0.01 mol/L
iodine VS, if necessary, add about 5 mL of carbon tetrachloride and shake. Titrate this solution with 0.01
mol/L sodium thiosulfate VS, perform a blank determination and make any necessary correction. Determine the
consumed amounts (mL) of 0.01 mol/L iodine VS, VT
and VS , of the test solution and the standard solution.
Amount (g) of penicillin G sodium (C16H17N2NaO4S)
= amount (g) of Penicillin G Sodium RS
VT
VS
Benzbromarone
CH2CH3
Br
OH
O
Br
C17H12Br2O3: 424.08
Benzbromarone, when dried, contains not less than
98.5% and not more than 101.0% of benzbromarone
(C17H12Br2O3).
Description Benzbromarone is a white to pale yellow

Benzbromarone is very soluble in dimethylformamide,
freely soluble in acetone or in chloroform, soluble in ether, sparingly soluble in ethanol and practically insoluble
in water.
the solutions of Benzbromarone and Benzbromarone RS
in 0.01 mol/L sodium hydroxide TS (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Benzbromarone
and Benzbromarone RS, previously dried, as directed in
Melting Point
Purity (1) SulfateDissolve 1.0 g of Benzbromarone

in 40 mL of acetone and add 1 mL of dilute hydrochloric
acid and water to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control solution as follows: to 0.40 mL of 0.005 mol/L sulfuric acid
VS add 40 mL of acetone, 1 mL of dilute hydrochloric
acid and water to make 50 mL (not more than 0.019%).
(2) Soluble halidesDissolve 0.5 g of Benzbromarone in 40 mL of acetone and add 6 mL of dilute nitric
acid and water to make 50 mL. Proceed with this solution as directed under the Chloride Limit Test. Prepare
the control solution as follows: to 0.25 mL of 0.01 mol/L
hydrochloric acid VS, add 40 mL of acetone, 6 mL of dilute nitric acid and water to make 50 mL.
(3) Heavy metalsProceed with 2.0 g of Benzbromarone according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(4) IronPrepare the test solution with 1.0 g of
Benzbromarone according to Method 3 and perform the
test according to Method A. Prepare the control solution
with 2.0 mL of standard iron solution (not more than 20
ppm).
(5) Related substancesDissolve 0.10 g of
Benzbromarone in 10 mL of chloroform and use this solution as the test solution. Pipet 1 mL of the test solution,
add chloroform to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
test solution and standard solution as directed under the
Develop the plate with a mixture of chloroform, acetone
and glacial acetic acid (100 : 2 : 1) to a distance of about
light (main wavelength: 254 nm): the spots other than the

at a pressure not exceeding 0.67 kPa, P2O5, 50 C, 4
hours).
Assay Weigh accurately about 0.6 g of Benzbromarone,
previously dried, dissolve in 30 mL of dimethylformamide and titrate with 0.1 mol/L tetramethylammonium
hydroxide VS (indicator: 5 drops of thymol bluedimethylformamide TS). Perform a blank determination
Each mL of 0.1 mol/L tetramethylammonium hydroxide
VS = 42.41 mg of Cl7Hl2Br2O3
tight containers.
CH3
C
CH3
CH3
CH2
C
CH3
Purity AmmoniumDissolve 0.1 g of Benzethonium

Chloride in 5 mL of water, add 3 mL of sodium hydroxide and boil this solution. The wet red litmus paper does
not change to blue in color by gas produced from the solution.
CH3
O(CH2)2O(CH2)2NCH2
Melting Point Between 158 C and 164 C (after drying).

hours).
Benzethonium Chloride
H3C
of Benzethonium Chloride and Benzethonium Chloride

RS in 0.1 mol/L hydrochloric acid VS (1 in 5000) as directed under the Ultraviolet-visible Spectrophotometry:
(4) To 1 mL of a solution of Benzethonium Chloride
(1 in 100), add 2 mL of ethanol, 0.5 mL of dilute nitric
acid and 1 mL of silver nitrate TS: a white precipitate is
produced. This precipitate does not dissolve on addition
of dilute nitric acid, but dissolves on addition of ammonia TS.
Cl
CH3
C27H42ClNO2: 448.08
Benzethonium Chloride, when dried, contains not less
than 97.0% and not more than 101.0% of benzethonium
chloride(C27H42ClNO2).
Description Benzethonium Chloride is a colorless or
white crystal and is odorless.
Benzethonium Chloride is very soluble in ethanol, freely
soluble in water and practically insoluble in ether.
A solution of Benzethonium Chloride foams strongly
when shaken.
Identification (1) Dissolve 0.2 g of Benzethonium
Chloride in 1 mL of sulfuric acid, add 0.1 g sodium nitrate and heat for 5 minutes in a water-bath. After cooling,
add 10 mL of water and 0.5 g of zinc powder, heat for 5
minutes, cool and filter: the filtrate responds to the Qualitative Tests for primary aromatic amines, with a red
color observed.
(2) To 2 mL of a solution of Benzethonium Chloride
(1 in 1000), add a mixture of 0.2 mL of a solution of
bromophenol blue (1 in 2000) and 0.5 mL of sodium hydroxide TS: a blue color is observed. Add 4 mL of chloroform to this solution and shake vigorously: the blue
color shifts to the chloroform layer. Collect the chloroform layer and add dropwise a solution of sodium lauryl
sulfate (1 in 1000) with stirring: the chloroform layer
turns colorless.
Assay Weigh accurately 0.2 g of Benzethonium Chloride, previously dried, dissolve in 75 mL of diluted dilute
hydrochloric acid (1 in 2) dropwise to adjust the pH 2.6
to 3.4, then add 1 drop of methyl orange TS and titrate
with 0.02 mol/L sodium tetraphenylboron VS until the
solution becomes red.
tight containers.
Benzethonium Chloride Solution

Benzethonium Chloride Solution contains not less than
of benzethonium chloride (C27H42ClNO2: 448.08).
Method of Preparation Dissolve Benzethonium Chloride in Water or Purified Water.
Description Benzethonium Chloride Solution is a clear,
colorless liquid and is odorless.
Benzethonium Chloride Solution foams strongly when
shaken.
Identification (1) Evaporate a volume of Benzethonium Chloride Solution, equivalent to 0.2 g of Benzethonium Chloride according to the labeled amount, on a water-bath to dryness and proceed with the residue as di-
KP 9 103
rected in the Identification (1) under Benzethonium
Chloride.
(2) To a volume of Benzethonium Chloride Solution,
equivalent to 10 mg of Benzethonium Chloride according to the labeled amount, add water to make 10 mL and
proceed with 2 mL of this solution as directed in the
Identification (2) under Benzethonium Chloride.
equivalent to 1 g of Benzethonium Chloride according to
the labeled amount, add water or concentrate on a waterbath, if necessary, to make 10 mL. To 1 mL of this solution, add 0.1 mol/L hydrochloric acid VS to make 500
mL, and determine the absorption spectrum as directed
under the Ultraviolet-visible Spectrophotometry : it exhibits maxima abetween 262 nm and 264 nm, between
268 nm and 270 nm, and between 274 nm and 276 nm.
equivalent to 0.1 g of Benzethonium Chloride according
to the labeled amount, add water or concentrate on a water-bath, if necessary, to make 10 mL and proceed with 1
under Benzethonium Chloride.
Purity (1) NitriteAdd 1.0 mL of Benzethonium
Chloride Solution to a mixture of 1 mL of a solution of
glycine (1 in 10) and 0.5 mL of dilute acetic acid: no gas
is evolved.
(2) Oxidizing substancesTo 5 mL of Benzethonium Chloride Solution, add 0.5 mL of potassium iodide
TS and 2 to 3 drops of dilute hydrochloric acid: no yellow color is observed.
Assay Pipet a volume of Benzethonium Chloride Solution, equivalent to about 0.2 g of benzethonium chloride
(C27H42ClNO2), dilute with water to make 75 mL, if necessary, and proceed as directed in the Assay under Benzethonium Chloride.
tight containers.
Benzoic Acid is freely soluble in ethanol, in acetone, or

in ether, soluble in hot water and slightly soluble in water.
Identification Dissolve 1 g of Benzoic Acid in 8 mL of
sodium hydroxide TS and add water to make 100 mL:
this solution responds to the Qualitative Tests (2) for
benzoate.
Melting Point
Purity (1) Heavy metalsDissolve 1.0 g of Benzoic

Acid in 25 mL of acetone, add 2 mL of dilute acetic acid
and water to make 50 mL and perform the test using this
as follows: to 2.0 mL of standard lead solution, add 2 mL
of dilute acetic acid, 25 mL of acetone and water to make
50 mL (not more than 20 ppm).
(2) Chlorinated compoundsTake 0.5 g of Benzoic
Acid and 0.7 g of calcium carbonate in a crucible, mix
with a small amount of water and dry. Ignite it at about
600 C, dissolve in 20 mL of dilute nitric acid and filter.
Wash the residue with 15 mL of water, combine the filtrate and the washing, add water to make 50 mL and add
0.5 mL of silver nitrate TS: this solution has no more
turbidity than the following control solution.
Control solutionDissolve 0.7 g of calcium carbonate in 20 mL of dilute nitric acid and filter. Wash the residue with 15 mL of water, combine the filtrate and the
washings, add 1.2 mL of 0.01 mol/L hydrochloric acid
VS and water to make 50 mL and add 0.5 mL of silver
nitrate TS.
(3) Potassium permanganate-reducing substancesAdd 0.02 mol/L potassium permanganate VS
drop-wise to a boiling mixture of 100 mL of water and
1.5 mL of sulfuric acid, until a red color persists for 30
seconds. Dissolve 1.0 g of Benzoic Acid in this boiling
solution and add 0.50 mL of 0.02 mol/L potassium permanganate VS: a red color persists for at least 15
seconds.
(4) Phthalic acidTo 0.10 g of Benzoic Acid, add 1
mL of water and 1 mL of resorcinsulfuric acid TS and
heat the mixture in an oil-bath heated at a temperature
o
Benzoic Acid
CO 2H
C7H6O2: 122.12
Benzoic Acid, when dried, contains not less than 99.5%
and not more than 101.0% of benzoic acid (C7H6O2).
Description Benzoic Acid is a white crystal or crystalline powder, is odorless, or has a faint, benzaldehyde-like
odor.
between 120 C and 125 C . After evaporating the water, heat the residue for 90 minutes, cool and dissolve in
5 mL of water. To 1 mL of the solution, add 10 mL of a
solution of sodium hydroxide (43 in 500), shake, then
examine under light at a wavelength between 470 nm
and 490 nm: the green fluorescence of the solution is not
more intense than of the following control solution.
Control solutionDissolve 61 mg of potassium
biphthalate in water to make exactly 1000 mL. Measure
exactly 1 mL of the solution, add 1 mL of resorcinsulfuric acid TS and proceed as directed above.
(5) Readily carbonizable substances Perform the

test using 0.5 g of Benzoic Acid. The solution has no
more color than Color Matching Fluid Q.
hours).
Residue on Ignition
Assay Weigh accurately about 0.5 g of Benzoic Acid,

previously dried, dissolve in 25 mL of neutralized ethanol and 25 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS).
= 12.212 mg of C7H6O2
Benzydamine Hydrochloride
HCl
N
N
N(CH3)2
C19H23N3OHCl : 345.87
Benzydamine Hydrochloride contains not less than
99.0% and not more than 101.0% of benzydamine hydrochloride (C19H23N3OHCl), calculated on the dried
basis.
Description Benzydamine Hydrochloride is a white
crystalline powder.
Benzydamine Hydrochloride is very soluble in water,
freely soluble in ethanol or in chloroform, and practically
insoluble in ether.
spectra of Benzydamine Hydrochloride and Benzydamine Hydrochloride RS as directed in the potassium
(2) The solution of Benzydamine Hydrochloride in
water (1 in 50) responds to the Qualitative Tests for chloride.
Benzydamine Hydrochloride in 10 mL of water is be-
tween 4.0 and 5.5.

Purity (1) Clarity and color of solutionWhen 1 g of
Benzydamine Hydrochloride is dissolved in 10 mL of
water, the resultant solution is clear.
(2) Heavy metals Proceed with 1.0 g of Benzydamine Hydrochloride according to Method 1 and perform
the thest. Prepare the control solution with 2.0 mL of
(3) Primary aminesDissolve 50 mg of Benzydamine Hydrochloride in 10 mL of ethanol, and add 0.1
mL of hydrochloric acid and 2 mL of the solution of 4dimethylaminobenzaldehyde in ethanol (1 in 20). The
yellow color obtained is not more intense than that obtained by treating 10 mL of the solution of 2aminobenzoic acid in ethanol (0.5 g/mL) in the same
manner.
(4) Related substancesDissolve 25 mg of Benzydamine Hydrochloride in a mixture of methanol and water (1 : 1) to make exactly 10 mL, and use this solution as
the test solution. Dissolve 5 mg of Benzydamine Hydrochloride
Related
Substance
I
RS
(3dimethylaminopropyl 2-benzylaminobenzoate hydrochloride) and 12.5 mg of Benzydamine Hydrochloride Related Substance II RS (3-(1,5-dibenzyl-1H-indazol-3yl)oxypropyldimethylamine hydrochloride) in a mixture
of methanol and water (1 : 1) to make exactly 100 mL.
Dilute 1.0 mL of this solution with a mixture of methanol
and water (1 : 1) to 10 mL, and use this solution as the
standard solution (1). Dissolve 2.5 mg of Benzydamine
Hydrochloride Related Substance III RS (1-benzyl-1Hindazol-3-ol) in a mixture of methanol and water (1 : 1)
to make exactly 100 mL. Pipet 1 mL of this solution, dilute with a mixture of methanol and water (1 : 1) to 10
mL, and use this solution as the standard solution (2). Dilute 0.1 mL of the test solution with a mixture of methanol and water (1 : 1) to 100 mL, and use the solution as
the standard solution (3). The standard solution (4) contains equal volumes of the test solution, the standard solution (1) and the standard solution (2). Perform the test
with 20 L each of the test solution and the standard solutions as directed under the Liquid Chromatography according to the following conditions. Determine the area
of each peak by the automatic integration method. The
areas of any peak corresponding to the related substance
I or the related substance II are not greater than the area
of the corresponding peak from the standard solution (1)
(not more than 0.2% of the related substance I; not more
than 0.5% of the related substance II); the area of any
peak corresponding to the related substance III is not
greater than the area of the peak from the standard solution (2) (0.1%); the area of any other secondary peak is
not greater than the area of the peak from the standard
solution (3) (0.1%); and the sum of the areas of any such
peaks is not greater than 1%.
KP 9 105
Column: A stainless steel column about 4.6 mm inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m
in particle diameter).
Column temperature: A a constant temperature of
about 25 o C .
Mobile phase: Variable mixtures of mobile A and
mobile phase B, and program the chromatograph as follows.
Mobile phase AAn aqueous solution containing
0.01 mol/L potassium dihydrogen phosphate and 0.005
mol/L sodium octyl sulphate, adjusted to pH 3.0 0.1
with phosphoric acid.
Mobile phase BMethanol.
Time (min)
0
0 ~ 20
20 ~ 22
22 ~ 30
Mobile
Mobile
phase A (%) phase B (%)
50
50
50 30
50 70
30 50
70 50
50
50
Elution
equilibrium
linear gradient
linear gradient
isocratic

System suitability
operating conditions, the retention time of benzydamine
is about 10 minutes, with the resolution between the peak
of benzydamine and any adjacent peak being not less
than 2.5.
Loss on Drying Not more than 0.5% (1 g, 0.67 kPa,
105 C, 3 hours).
Assay Dissolve 0.3 g of Benzydamine Hydrochloride,
accurately weighed, in 100 mL of glacial acetic acid, and
titrate with 0.1 mol/L perchloric acid VS (potentiometric
= 34.59 mg of C19H23N3OHCl
Berberine Chloride Hydrate

O
O
Cl-
XH2O
N
CH3O
CH3O
Berberine Hydrochloride
Berberine Chloride
C20H18ClNO4xH2O
Berberine Chloride Hydrate contains not less than 95.0%

and not more than 102.0% of berberine chloride
(C20H18ClNO4: 371.81) calculated on the anhydrous basis.
Description Berberine Chloride Hydrate is a yellow
crystal or crystalline powder, is odorless or has a faint,
characteristic odor and has a very bitter taste.
Berberine Chloride Hydrate is sparingly soluble in methanol, slightly soluble in ethanol, and very slightly soluble in water.
the solutions of Berberine Chloride Hydrate and Berberine Chloride Hydrate RS ( 1 in 100000 ) as directed under the Ultraviolet-visible Spetrophotometry: both spectra exhibit similar intensities at the same wavelengths.
(2) Determine the infrared spectra of Berberine Chloride Hydrate and Berberine Chloride Hydrate RS as directed in the potassium bromide disk method under the
(3) Dissolve 0.1 g of Berberine Chloride Hydrate in
20 mL of water by warming, add 0.5 mL of nitric acid,
cool and filter after allowing to stand for 10 minutes. To
3 mL of the filtrate, add 1 mL of silver nitrate TS and
collect the produced precipitate: the precipitate does not
dissolve in dilute nitric acid, but it dissolves in an excess
amount of ammonia TS.
Purity (1) AcidShake thoroughly 0.10 g of Berberine Chloride Hydrate with 30 mL of water and filter. To
the filtrate, add 2 drops of phenolphthalein TS and 0.10
mL of 0.1 mol/L sodium hydroxide VS: the yellow color
changes to an orange to red color.
(2) SulfateShake 1.0 g of Berberine Chloride Hydrate with 48 mL of water and 2 mL of dilute hydrochloric acid for 1 minute and filter. Discard the first 5 mL
of the filtrate, take the subsequent 25 mL of the filtrate,
add water to make 50 mL and perform the test with this

with 0.50 mL of 0.005 mol/L sulfuric acid VS, 1 mL of
dilute hydrochloric acid, 5 to 10 drops of bromophenol
blue TS and water to make 50 mL (not more than
0.048%).
(3) Heavy metalsProceed with 1.0 g of Berberine
Chloride Hydrate according to Method 2 and perform the
(4) Related substancesDissolve 10 mg of Berberine Chloride Hydrate in 100 mL of mobile phase and
use this solution as the test solution. Pipet 4 mL of the
test solution, add the mobile phase to make exactly 100
mL, use this solution as the standard solution. Perform
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine
each peak area of both solutions by the automatic integration method: total of the peak areas of peaks other
than berberine of the test solution is not larger than the
peak area of berberine of the standard solution.
flow rate and selection of column: Proceed as directed in
the operating conditions in the Assay.
the retention time of berberine, after the solvent peak.
Detection sensitivity: Adjust the detection sensitivity
so that the peak height of berberine obtained from 10 L
of the standard solution is about 10 % of the full scale.
Water 8.0% to 12.0% (0.1 g, volumetric titration, direct titration).
Assay Weigh accurately 10 mg of Berberine Chloride
Hydrate and dissolve in mobile phase to make exactly
100 mL and use this solution as the test solution. Separately, weigh accurately about 10 mg of Berberine Chloride Hydrate RS (separately determined water content)
and dissolve in the mobile phase to make exactly 100 mL
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the
peak areas, AT and AS of berberine in each solution.
Amount (mg) of berberine chloride (C20H18ClNO4)
= amount (mg) of Berberine Chloride Hydrate RS,
AT
AS
Detector: An ultraviolet absorption photometer (wavelength: 345nm).
Column: A stainless steel column about 4 mm in inside diameter and about 25 cm in length, packed with oc-
tadecylsilanized silica gel for liquid chromatography (5

o
about 40 C .
Mobile phase: Dissolve 3.4 g of monobasic potassium phosphate and 1.7 g of sodium lauryl sufate in 1000
mL of a mixture of water and acetonitrile (1 : 1).
time of berberine is about 10 minutes.
Selection of column: Dissolve each 1 mg of berberine chloride and palmatin chloride in the mobile phase
to make 10 mL. Proceed with 10 L of this solution under the above operating conditions and calculate the
resolution. Use a column giving elution of palmatin and
berberine in this order with the resolution between these
peaks being not less than 1.5 %.
tight containers.
Berberine Tannate
Berberine Tannate is a compound of berberine and tannic
acid. Berberine Tannate contains not less than 27.0% and
not more than 33.0% of berberine (C20H19NO5: 353.37),
Description Berberine Tannate is a yellow to pale yellow-brown powder, is odorless or has a faint, characteristic odor and is tasteless.
Berberine Tannate is practically insoluble in water, in
methanol, in ethanol or in ether.
Identification (1) To 0.1 g of Berberine Tannate, add
10 mL of ethanol and heat in a water-bath for 3 minutes
with shaking. Cool, filter and to 5 mL of the filtrate, add
1 drop of ferric chloride TS: a blue-green color is produced and on allowing to stand, a bluish black precipitate
is formed.
(2) Dissolve 10 mg of Berberine Tannate and Berberine Tannate RS in 10 mL of methanol and 0.4 mL of 1
mol/L hydrochloric acid TS and add water to make 200
mL. To each 8 mL of these solutions add water to make
25 mL. Determine the absorption spectra of the solutions
as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption
at the same wavelengths.
(3) Determine the infrared spectra of Berberine Tannate and Berberine Tannate RS, previously dried, as directly in the potassium bromide disk method under the
Purity (1) Acid To 0.10 g of Berberine Tannate add
30 mL of water and filter after shaking well. To the filtrate add 2 drops of phenolphthalein TS and 0.10 mL of
KP 9 107
0.1 mol/L sodium hydroxide VS: the color of the solution changes from yellow to orange to red.
(2) Chloride Shake 1.0 g of Berberine Tannate
with 38 mL of water and 12 mL of dilute nitric acid for 5
minutes and filter. Discard the first 5 mL of the filtrate,
to 25 mL of the subsequent filtrate, add water to make 50
mL and perform the test using this solution as the test solution. Prepare the control solution with 0.50 mL of 0.01
mol/L hydrochloric acid VS by adding 6 mL of dilute nitric acid, 10 to 15 drops of bromophenol blue TS and water to make 50 mL (not more than 0.035%).
(3) SulfateShake 1.0 g of Berberine Tannate with
48 mL of water and 2 mL of dilute hydrochloric acid for
1 minute and filter. Discard the first 5 mL of the filtrate,
take the subsequent 25 mL of the filtrate, add water to
mL of 0.005 mol/L sulfuric acid VS, 1 mL of dilute hydrochloric acid, 5 to 10 drops of bromphenol blue TS and
water to make 50 mL (not more than 0.048%).
(4) Heavy metalsProceed with 1.0 g of Berberine
Tannate according to Method 2 and perform the test.
(5) Related substancesDissolve 10 mg of Berberine Tannate in 100 mL of the mobile phase and use this
solution as the test solution. Pipet 4 mL of the test solution, add the mobile phase to make exactly 100 mL and
solution as directed under the Liquid Chromatography
according to the following conditions. Determine each
peak area of both solutions by the automatic integration
method: the total of the peak areas other than berberine
of the test solution is not larger than the peak area of
berberine of the standard solution.
Operating conditions.
the operating conditions in the Assay.
Test for required detectability: To exactly 2 mL of the
standard solution, add the mobile phase to make exactly
20 mL. Confirm that the peak area of berberine obtained
that with 10 L of the standard solution
so that the peak height of berberine obtained from 10 L
of the standard solution is about 10 % of the full scale.
the retention time of berberine, after the solvent peak.
direct titration).
Assay Weigh accurately 30 mg of Berberine Tannate
and dissolve in mobile phase to make exactly 100 mL

weigh accurately about 10 mg of Berberine Chloride RS
(separately determined water content) and dissolve in the
mobile phase to make exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L
the following conditions. Determine the peak areas, AT
and AS of berberine in each solution.
Amount (mg) of berberine (C20H19NO5)
= amount (mg) of Berberine Chloride RS,
AT
0.9504
AS
Column: A stainless steel column about 4 mm in inside diameter and about 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
about 40 C.
Mobile phase: Dissolve 3.4 g of monobasic potassium phosphate and 1.7 g of sodium lauryl sufate in 1000
mL of a mixture of water and acetonitrile (1 : 1).
time of berberine is about 10 minutes.
Selection of column: Dissolve each 1 mg of Berberine Chloride and palmatin chloride in the mobile phase
to make 10 mL. Proceed with 10 L of this solution under the above operating conditions and calculate the
resolution. Use a column giving elution of palmatin and
berberine in this order with the resolution between these
peaks being not less than 1.5%.
tight containers.
Betahistine Mesilate
N
CH2CH2NHCH3
2 CH3SO3H
C8H12N22CH4O3S: 328.41
Betahistine Mesilate, when dried, contains not less than
98.0% and not more than 101.0% of betahistine mesilate(C8H12N22CH4O3S).
Description Betahistine Mesilate is a white crystal or
crystalline powder.
Betahistine Mesilate is very soluble in water, freely soluble in methanol or in glacial acetic acid, sparingly so-

luble in dehydrated ethanol, very slightly soluble in acetic anhydride and practically insoluble in ether.
Betahistine Mesilate dissolves in dilute hydrochloric acid.
Betahistine Mesilate is hygroscopic.
the solutions of Betahistine Mesilate and Betahistine Mesilate RS in 0.1 mol/L hydrochloric acid (1 in 50000) as
(2) Determine the infrared spectra of Betahistine Mesilate and Betahistine Mesilate RS, previously dried, as
(3) To 30 mg of Betahistine Mesilate, add 0.1 g of
sodium nitrate and 0.1 g of anhydrous sodium carbonate,
mix well and ignite gradually. After cooling, dissolve the
residue in 2 mL of dilute hydrochloric acid and 10 mL of
water, filter, if necessary and to the filtrate, add 1 mL of
barium chloride TS: a white precipitate is produced.
Melting Point Between 110 C and 114 C (after drying).
Purity (1) Heavy metalsProceed with 1.0 g of Betahistine Mesilate according to Method 4 and perform the
(2) Related substancesDissolve 50 mg of Betahistine Mesilate in 10 mL of a mixture of water and acetonitrile (63:37), and use this solution as the test solution. Pipet 1 mL of the test solution, add the mixture of water
and acetonitrile (63:37) to make exactly 100 mL, and use
this solutions as the standard solution. Perform the test
with the test solution and the standard solution as directed under the Liquid Chromatography according to
the following conditions, and determine each peak area
by the automatic integration method: the area of the peak
other than betahistine with the test solution is not larger
than 1/10 times the peak area of betahistine with the
standard solution, and the total area of the peaks other
than the peak area betahistine with the test solution is not
larger than 1/2 times the peak area of betahistine with the
standard solution.
about 35 C.
Mobile phase: To 5 mL of diethyl amine and 20 mL
of acetic anhydride, add water to make 1000 mL. Dissolve 2.3 g of sodium lauryl sulfate in 630 mL of this so-
lution, and add 370 mL of acetonitrile.

time of betahistine is about 5 minutes.
System suitability
the standard solution, add the mixture of water and acetonitrile (63:37) to make exactly 50 mL. Confirm that the
peak area of betahistine obtained with 20 L of this solution is equivalent to 7 to 13% of that with 20 L of the
standard solution.
System performance: Dissolve 10 mg of betahistine mesilate and 10 mg of 2-vinylpyridine in 50 mL of
the mixture of water and acetonitrile (63:37). To 2 mL of
this solution, add the mixture of water and acetonitrile
(63:37) to make 50 mL. When the procedure is run with
20 L of this solution under the above operating conditions, 2-vinylpyridine and betahistine are eluted in this
order with the resolution between these peaks being not
less than 5.
above operating conditions, the relative standard deviation of the peak area of betahistine is not more than 1.0%.
Time span of measurement: About twice as long as
the retention time of betohistine after the solvent peak.
Loss on Drying Not more than 1.0% (1 g, in vacuum,
P2O5, 70 C, 24 hours).
Residue on Ignition
Assay Weigh accurately 0.2 g of Betahistine Mesilate,

previously dried, dissolve in 1 mL of glacial acetic acid,
add 50 mL of acetic anhydride and titrate with 0.1 mol/L
= 16.420 mg of C8H12N22CH4O3S
Betamethasone
O
H
H3C
CH2OH
OH
HO
H
H3C
H
CH3
C22H29FO5: 392.46
Betamethasone, when dried, contains not less than 96.0%
and not more than 103.0% of betamethasone
(C22H29FO5).
KP 9 109
Description Betamethasone is a white to pale yellowish white, crystalline powder and is odorless.
Betamethasone is sparingly soluble in methanol, in ethanol, in acetone or in dioxane, very slightly soluble in ether or in chloroform and practically insoluble in water.
Identification (1) Proceed 10 mg of Betamethasone as
directed under the Oxygen Flask Combustion Method,
using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as an absorbing liquid and
prepare the test solution: the test solution so obtained responds to the Qualitative Tests for fluoride.
(2) Dissolve 1.0 mg each of Betamethasone and Betamethasone RS in 10 mL each of ethanol. To 2.0 mL
each of these solutions, add 10 mL each of phenylhydrazine hydrochloride TS, mix by shaking, heat in a waterbath at 60 C for 20 minutes. After cooling, determine the
absorption spectra of these solutions as directed under
the Ultraviolet-visible Spectrophotometry using a solution, prepared with 2.0 mL of ethanol in the same manner,
as the blank: both spectra exhibit similar intensities of
(3) Determine the infrared spectra of Betamethasone
and Betamethasone RS, previously dried, according to
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve each of Betamethasone and Betamethasone RS in acetone, evaporate to dryness and repeat the test on the residues.
D : Between +118 and
+126 (after drying, 0.1 g, methanol, 20 mL, 100 mm).
Purity (1) Heavy metalsProceed with 0.5 g of Betamethasone according to Method 2 and perform the test.
Prepare the control solution with 1.5 mL of standard
(2) Related substancesDissolve 10 mg of Betamethasone in 5 mL of a mixture of chloroform and methanol (9 : 1) and use this solution as the test solution. Pipet
1 mL of the test solution, add a mixture of chloroform
and methanol (9 : 1) to make exactly 100 mL and use this
the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 5 L each of
silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, ether, methanol and water (385 : 75 : 40 : 6)
to a distance of about 12 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm):
the spots other than the principal spot from the test solution are not more intense than the spot from the standard
solution.

P2O5, 4 hours).
Residue on Ignition Not more than 0.5% (0.1 g, platinum crucible).
Assay Dissolve about 20 mg each of Betamethasone
and Betamethasone RS, previously dried and accurately
weighed, in methanol to make exactly 50 mL. Pipet 5 mL
each of these solutions, add exactly 5 mL each of the internal standard solution, then add methanol to make 50
and QS , of the peak area of betamethasone to that of the
internal standard, for the test solution and the standard
solution, respectively.
Amount (mg) of betamethasone (C22H29FO5)
= amount (mg) of Betamethasone RS QT
QS
Internal standard solutionA solution of butyl parahydroxybenzoate in methanol (1 in 1750).

Column: A stainless steel column, about 4 mm in inside diameter and 15 to 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
Mobile phase: A mixture of water and acetonitrile (3 :
2).
time of betamethasone is about 4 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, betamethasone and the internal standard are eluted in this order with the resolution between
these peaks being not less than 10.
times with 10 L each of the standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak area of betamethasone to
that of the internal standard is not more than 1.0%.
tight containers.
Betamethasone Tablets
=WS
AT V ' 1 9

AS V C 5
WS : Amount (mg) of Betamethasone RS

Betamethasone Tablets contain not less than 90.0% and
not more than 107.0% of the labeled amount of betamethasone (C22H29FO5: 392.46).
Method of Preparation Prepare as directed under Tablets, with Betamethasone.
Identification Pulverize Betamethasone Tablets. To a
portion of the powder, equivalent to 2 mg of Betamethasone according to the labeled amount, add 20 mL of methanol, shake for 5 minutes, and filter. Evaporate the filtrate on a water bath to dryness, dissolve the residue after
cooling in 2 mL of methanol, filter if necessary, and use
the solution as the test solution. Separately, dissolve 2
mg of Betamethasone RS in 2 mL of methanol, and use
and the standard solution on the plate of silica gel with a
fluorescent indicator for thin-layer chromatography, develop with a mixture of 1-butanol, water and acetic anhydride (3:1:1) to a distance of about 10 cm, and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal spots from the test solution
and the standard solution show the same Rf value.
Dissolution Test Perform the test with 1 tablet of Betamethasone Tablets at 50 revolutions per minute according to the paddle method under the Dissolution Test, using the mixture of 900 mL of water as the dissolution
medium. Withdraw 20 mL or more of the dissolution
medium 30 minutes after starting the test, and filter
through a membrane filter with a pore size not exceeding
0.45 m. Discard the first 10 mL of the filtrate, pipet the
subsequent V mL of the filtrate, add water to make exactly V mL so that each mL contains about 0.56 g of betamethasone (C22H29FO5) according to the labeled
amount, and use this solution as the test solution. Separately, weigh accurately about 28 mg of Betamethasone
RS, previously dried in a desiccator (in vacuum, P2O5)
for 4 hours, dissolve in methanol to make exactly 100
mL. Pipet 5 mL of this solution, and use this solution as
under the Liquid Chromatography according to the following conditions, and determine the peak areas, AT
and AS , of betamethasone for the test solution and the
standard solution. The dissolution rate in 30 minutes is
not less than 85%.
of betamethasone (C22H29FO5)
C: Labeled amount
(C22H29FO5) in 1 tablet
(mg)
of
betamethasone
about 25 C.
Mobile phase: A mixture of methanol and water (3:2).
System suitability
the symmetry factor of the peak of betamethasone are not
above operating conditions, the relative standard deviation of the peak area of betamethasone is not more than
1.0%.
Uniformity of Dosage Units It meets the requirement,
when the content uniformity test is performed according
to the following method.
To 1 tablet of Betamethasone Tablets, add V mL of water
so that each mL contains about 50 g of betamethasone
(C22H29FO5) according to the labeled amount, add exactly an amount of the internal standard solution equivalent
to 2 mL per 50 g of betamethasone, shake vigorously
for 10 minutes, centrifuge, and use the supernatant liquid
20 mg of Betamethasone RS, previously dried in a desiccator (in vacuum, P2O5) for 4 hours, and dissolve in acetonitrile to make exactly 200 mL. Pipet 5 mL of this solution, add exactly 20 mL of the internal standard solution, and use this solution as the standard solution. Perform the test with 50 g each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS , of the peak area of betamethasone to that of the internal standard for the test
solution and the standard solution.
= Amount (mg) of Betamethasone RS
QT
V
Q S 400
KP 9 111
Internal standard solutionA solution of butyl parahydroxybenzoate in acetonitrile (1 in 40000)

Operating conditionsProceed as directed in the assay.
System suitability
with 50 L of the standard solution under the above operating conditions, betamethasone and the internal standard are eluted in this order with the resolution between
System repeatability: When the test is run 6 times
with 50 L of the standard solution under the above operating conditions, the relative standard deviation of the
ratio of the peak area of betamethasone to that of the internal standard is not more than 1.0%.
Assay Weigh accurately not less than 20 Betamethasone Tablets and powder. Weigh accurately a portion of
powder, equivalent to about 5 mg of betamethasone(C22H29FO5), add 25 mL of water, then add exactly
50 mL of the internal standard solution, and shake vigorously for 10 minutes. Filter through a membrane filter
with pore size of not more than 0.5 m, discard the first
5 mL of the filtrate, and use the subsequent filtrate as the
of Betamethasone, previously dried in a desiccator (in
vacuum, P2O5) for 4 hours, and dissolve in acetonitrile to
make exactly 20 mL of the internal standard solution.
the standard solution as directed under the Liquid Chromatography according to the following conditions, and
determine the ratios, QT and QS , of the peak area of
betamethasone to that of the internal standard for the test
solution and the standard solution.
= Amount (mg) of Betamethasone RS
QT 1
QS 4
Internal standard solutionA solution of butyl parahydroxybenzoate in acetonitrile (1 in 10000).

Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
about 25 C.
Mobile phase: A mixture of water and acetonitrile
(3:2).
System suitability
with 20 L of the standard solution under the above operating conditions, Betamethasone and internal standard
is eluted in this order with the resolution between these
times with the standard solution under the above operating conditions, the relative standard deviation of the ratios of the peak area of betamethasone to that of the internal standard is not more than 2.0%.
Betamethasone Dipropionate
O
O
H
H3C
HO
CH2O
O
O
H3C
CH2CH3
CH2CH3
CH3
H
C28H37FO7: 504.59
Betamethasone Dipropionate, when dried, contains not
less than 97.0% and not more than 103.0% of betamethasone dipropionate (C28H37FO7) and not less than 3.4%
and not more than 4.1% of fluorine (F: 19.00)..
Description Betamethasone Dipropionate is a white to
pale yellowish white, crystalline powder and is odorless.
Betamethasone Dipropionate is freely soluble in acetone,
in dioxane or in chloroform, soluble in methanol, sparingly soluble in ethanol, slightly soluble in ether and
practically insoluble in water or in hexane.
Betamethasone Dipropionate is gradually affected by
light.
Identification (1) To 1 mL of a solution of Betamethasone Dipropionate in methanol (1 in 10000), add 4 mL of
isoniazid TS and heat in a water-bath for 2 minutes: a
yellow color is observed.
(2) Proceed with 10 mg of Betamethasone Dipropionate as directed under the Oxygen Flask Combustion
Method, using a mixture of 0.5 mL of 0.01 mol/L sodium
hydroxide TS and 20 mL of water as the absorbing liquid: the test solution so obtained responds to the Qualitative Tests for fluoride.
of Betamethasone Dipropionate and Betamethasone Dipropionate RS in methanol (3 in 200000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavelengths.
Dipropionate and Betamethasone Dipropionate RS, pre-

viously dried, as directed in the potassium bromide disk
same wavenumbers.
D : Between +63 and
+70 (after drying, 50 mg, dioxane, 10 mL, 100 mm).
Purity (1) FluorideTo 0.10 g of Betamethasone Dipropionate, add 10.0 mL of diluted 0.01 mol/L sodium
hydroxide TS (1 in 20), shake for 10 minutes and filter
through a membrane filter (0.4 m pore size). Place 5.0
mL of the filtrate in a volumetric flask and add 10 mL of
a mixture of alizalin complexone TS, acetic acidpotassium acetate buffer solution, pH 4.3 and cerous nitrate TS (1 : 1 : 1), add water to make 20 mL, allow to
stand for 1 hour and use this solution as the test solution.
Separately, place 1.0 mL of standard fluorine solution in
a volumetric flask, add 5.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20), then 10 mL of a mixture of
alizarin complexone TS, acetic acid-potassium acetate
buffer solution, pH 4.3 and cerous nitrate TS (1 : 1 : 1),
proceed in the same manner as the preparation of the test
solution and use this solution as the standard solution.
Place 5.0 mL of diluted 0.01 mol/L sodium hydroxide TS
(1 in 20) in a volumetric flask, proceed in the same manner as the preparation of the test solution and use this solution as the blank. Determine the absorbances of the test
solution and the standard solution at 600 nm as directed
under the Ultraviolet-visible Spectrophotometry: the absorbance of the test solution is not greater than that of the
standard solution (not more than 0.012%).
(2) Heavy metalsProceed with 1.0 g of Betamethasone Dipropionate according to Method 2 and perform
(3) Related substancesPerform the test without
exposure to daylight using light-resistant vessels. Dissolve 10 mg of Betamethasone Dipropionate in 10 mL of
chloroform and use this solution as the test solution. Pipet 3 mL of the test solution, add chloroform to make exactly 100 mL and use this solution as the standard solution. Perform the test as directed under the Thin-layer
Chromatography with the test solution and the standard
solution. Spot 20 L each of the test solution and the
standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop
the plate with a mixture of chloroform and acetone (7 : 1)
to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm):
solution.
hours).

Assay (1) Betamethasone DipropionateWeigh accurately 15 mg of Betamethasone Dipropionate, previously
dried and dissolve in methanol to make exactly 100 mL.
Pipet 5 mL of this solution and dilute with methanol to
make exactly 50 mL. Determine the absorbance A of this
solution at the wavelength of a maximum absorption at
about 239 nm as directed under the Ultraviolet-visible
Spectrophotometry.
Amount (mg) of betamethasone dipropionate
A
(C28H37FO7) = 312 10000
(2) FluorineWeigh accurately 10 mg of Betamethasone Dipropionate, previously dried and proceed as
directed in the determination for fluorine under the Oxygen Flask Combustion Method, using a mixture of 0.5
mL of 0.01 mol/L sodium hydroxide TS and 20 mL of
water as the absorbing liquid.

tight containers.
Betamethasone Sodium
Phosphate
O
H3C
H
HO
CH2OPO3Na2
OH
H
H3C
CH3
F
C22H28FNa2O8P: 516.41
Betamethasone Sodium Phosphate contains not less than
97.0% and not more than 103.0% of betamethasone sodium phosphate (C22H28FNa2O8P), calculated on the anhydrous basis.
Description Betamethasone Sodium Phosphate is a
white to pale yellowish white, crystalline powder or mass
and is odorless.
Betamethasone Sodium Phosphate is freely soluble in
water, sparingly soluble in methanol, slightly soluble in
Betamethasone Sodium Phosphate is hygroscopic.
Identification (1) Dissolve 2 mg of Betamethasone
Sodium Phosphate in 2 mL of sulfuric acid: a brown col-
KP 9 113
or develops and gradually changes to blackish brown.
(2) Prepare the test solution with 10 mg of Betamethasone Sodium Phosphate as directed under the Oxygen
Flask Combustion Method, using a mixture of 0.5 mL of
0.01 mol/L sodium hydroxide TS and 20 mL of water as
an absorbing liquid: the test solution responds to the Qualitative Tests (2) for fluoride.
(3) Take 40 mg of Betamethasone Sodium Phosphate
in a platinum crucible and carbonize by heating. After
cooling, add 5 drops of nitric acid and incinerate by heating. To the residue, add 10 mL of diluted nitric acid (1 in
50) and boil for several minutes. After cooling, neutralize
the solution with ammonia TS, filter, if necessary and use
this solution as the test solution. The test solution responds to the Qualitative Tests for sodium salt and for
phosphate.
Sodium Phosphate and Betamethasone Sodium Phosphate RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
D : Between +99 and
+105 (0.1 g, calculated on the anhydrous basis, water,
10 mL, 100 mm).
pH Dissolve 0.10 g of Betamethasone Sodium Phosphate in 20 mL of water: the pH of this solution is between 7.5 and 9.0.
Purify (1) Clarity and color of solutionDissolve
0.25 g of Betamethasone Sodium Phosphate in 10 mL of
(2) Free phosphoric acidWeigh accurately about
20 mg of Betamethasone Sodium Phosphate, dissolve in
20 mL of water and use this solution as the test solution.
Separately, pipet 4 mL of phosphoric acid standard solution, add 20 mL of water and use this solution as the
standard solution,. To each of the test solution and the
standard solution, add exactly 7 mL of dilute sulfuric acid, exactly 2 mL of ammonium molybdate-sulfuric acid
TS and exactly 2 mL of p-methylaminophenol sulfate TS,
shake well and allow to stand at 20 1 oC for 15 minutes.
To each, add water to make exactly 50 mL and allow to
stand at 20 1 oC for 15 minutes. Perform the test with
the test solution and the standard solutions as directed
under the Ultraviolet-visible Spectrophotometry, using a
solution prepared with 20 mL of water in the same manner as the blank. Determine the absorbances, AT and
AS , of the test solution and the standard solution, respectively, at 730 nm: the amount of free phosphoric acid
is not more than 0.5%.
Amount (%) of free phosphoric acid (H3PO4)
=
AT
1
10 . 32
AS W
W: Amount (mg) of Betamethasone Sodium Phosphate, calculated on the anhydrous basis.

(3) BetamethasoneDissolve 20 mg of Betamethasone Sodium Phosphate in exactly 2 mL of methanol and
use this solution as the test solution. Separately, dissolve
20 mg of Betamethasone RS in exactly 10 mL of methanol. Pipet 1 mL of this solution, add methanol to make
exactly 20 mL and use this solution as the standard solution. Perform the test with the test solution and the standard solutions as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the
standard solution on a plate of silica gel with fluorescent
indicator for thin-layer chromatography. Develop the
plate with a freshly prepared mixture of n-butanol, water
and acetic anhydride (3 : 1 : 1) to a distance of about 10
(main wavelength: 254 nm): the spot from the test solution corresponding to the spot from the standard solution
is not more intense than the spot from the standard solution.
Water Not more than 10.0% (0.2 g, volumetric titration, back titration).
Assay Weigh accurately about 20 mg each of Betamethasone Sodium Phosphate and Betamethasone Sodium
Phosphate RS (determined its water content before using
in the same manner as Betamethasone Sodium Phosphate) and dissolve each in methanol to make exactly 20
mL. Pipet 5 mL each of these solutions, add exactly 5
mL of the internal standard solution, then add methanol
to make 50 mL and use these solutions as the test solution and the standard solution, respectively. Perform the
according to the following conditions and calculate the
ratios, QT and QS , of the peak area of betamethasone
phosphate to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of betamethasone sodium phosphate
(C22H28FNa2O8P) = amount (mg) of dried Betamethasone
Sodium Phosphate RS QT
QS
Internal Standard solutionA solution of butyl parahydroxybenzoate in methanol (1 in 5000).


about 25 C .
Mobile phase: Dissolve 1.6 g of tetra-nbutylammonium bromide, 3.2 g of dibasic sodium phosphate and 6.9 g of monobasic potassium phosphate in
1000 mL of water and add 1500 mL of methanol.
time of betamethasone phosphate is about 5 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, betamethasone phosphate and the internal standard are eluted in this order with the resolution
between these peaks being not less than 10.
System repeatability: When the procedure is run 6
above operating conditions, the relative standard deivation o the ratios of the peak area of betamethasone phosphate to that of the internal standard is not more than
1.0%.
Betamethasone Valerate
O
H
H3C
HO
CH3
CH2OH
O

hours).
CH2CH2CH2CH3
H
CH3
Purity Related substancesPerform this procedure

without exposure to light. Dissolve 20 mg of Betamethasone Valerate in 5 mL of a mixture of chloroform and
methanol (9 : 1) and use this solution as the test solution.
Pipet 1 mL of the test solution, add a mixture of chloroform and methanol (9 : 1) to make exactly 50 mL and use
with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 5 L
each of the test solution and the standard solution on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform and methanol
(9 : 1) to a distance of about 12 cm and air-dry the plate.
Spray evenly alkaline blue tetrazolium TS on the plate:
solution.
O
C

D : Between +77 and
+83 (after drying, 0.10 g, methanol, 20 mL, 100 mm)
C27H37FO6: 476.58
Betamethasone Valerate, when dried, contains not less
than 97.0% and not more than 103.0% of betamethasone
valerate (C27H37FO6).
Description Betamethasone Valerate is a white crystalline powder and is odorless.
Betamethasone Valerate is freely soluble in chloroform,
soluble in ethanol, sparingly soluble in methanol, slightly
soluble in ether and practically insoluble in water.
Identification (1) Proceed with 10 mg of Betamethasone Valerate as directed under the Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L
sodium hydroxide TS and 20 mL of water as the absorbing liquid and prepare the test solution: the test solution
responds to the Qualitative Tests for fluoride.
Valerate and Betamethasone Valerate RS, previously
Assay Dissolve about 10 mg each of Betamethasone

Valerate and Betamethasone Valerate RS, previously
dried and accurately weighed, in methanol to make exactly 100 mL. Pipet 10 mL each of these solutions, add
10 mL each of the internal standard solution and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the
operation conditions and calculate the ratios, QT and
QS , of the peak area of Betamethasone Valerate to that

of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of Betamethasone Valerate (C27H37FO6)
= amount (mg) of Betamethasone Valerate RS
QT
QS
Internal standard solutionA solution of isoamyl

benzoate in methanol (1 in 1000).
KP 9 115
about 25 C.
Mobile phase: A mixture of methanol and water (7 :
3).
time of Betamethasone Valerate is about 10 minutes.
Selection of column: Proceed with 10 L of the standard solution under the above operating conditions and
calculate the resolution. Use a column giving elution of
Betamethasone Valerate and the internal standard in this
order with the resolution between their peaks being not
less than 5.
Betaxolol Hydrochloride
O
CH3
N
H
CH3
H
Cl
OH
C18H29NO3HCl : 343.89)
Betaxolol Hydrochloride contains not less than 98.5%
and not more than 101.5% of betaxolol hydrochloride
(C18H29 NO3HCl), calculated on the dried basis.
Description Betaxolol Hydrochloride is a white, crystalline powder.
Betaxolol Hydrochloride is freely soluble in water, in
methanol, or in chloroform.
spectra of Betaxolol Hydrochloride and Betaxolol Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) When the solution of Betaxolol Hydrochloride (1
in 100) is mixed with 1 drop of dilute nitric acid, it responds to the Qualitative Tests for chloride.
Melting Point
Amount (%) of each related substance = 100
Ai
AS
Ai is the peak area of each individual peak, other

than the main betaxolol peak
AS is the sum of all peak areas
10 mL, and use this solution as the test solution. Perform

the test with 20 L of the test solution as directed under
conditions, and determine the area for the peaks. Calculate the percentage of each impurity according to the
peak area percentage method. The sum of all impurities
found is not more than 1.0%.

Betaxolol Hydrochloride in 50 mL of water is between
4.5 and 6.5.
Purity (1) Heavy metalsProceed with 1.0 g of Betaxolol Hydrochloride, according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
(2) Related substancesDissolve 20.0 mg of Betaxolol Hydrochloride in the mobile phase to make exactly
Column: A stainless steel column 4.6 mm inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase: a mixture of buffer solution and acetonitrile (85:15)
Flow rate: 1.5 mL/min
System suitability
System performance: Dissolve 20 mg of Betaxolol
Hydrochloride RS and 10 mg of alprenolol hydrochloride
in 10 mL, and use this solution as the resolution solution.
When the procedure is run with 20 L of the resolution
solution according to the above operating conditions, the
relative retention times are about 0.9 for alprenolol and
1.0 for betaxolol, the resolution between the two peaks is
not less than 1.0, and the symmetry factors for the two
peaks is not more than 2.0.
times with 20 L of the resolution solution according to
the above conditions, the relative standard deviation of
the peak area of betaxolol is not more than 2.0%.
Buffer solution Prepare a solution of 0.025 mol/L
monobasic potassium phosphate containing 0.1 % of tetrabutylammonium bromide. Adjust with 0.025 mol/L
phosphoric acid to a pH of 3.0.
hours)
Residue on Ignition Not more than 0.1% (1 g)
Assay Dissolve about 300 mg of Betaxolol Hydrochloride, accurately weighed, in 50 mL of glacial acetic acid,
add 7 mL of mercuric acetate TS, and titrate with 0.1 N
Detection Method in Titrimetry). Perform a blank determination, and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid VS = 34.39 mg of

C18H29NO3HCl.
Bethanechol Chloride
H
CH3CCH2N(CH3)3
Cl
OCONH2
and enantiomer
C7H17ClN2O2: 196.68
Bethanechol Chloride, when dried, contains not less than

98.0% and not more than 101.0% of bethanechol chloride (C7H17ClN2O2).
Description Bethanechol Chloride is a colorless or
white crystal or a white, crystalline powder. Bethanechol
Chloride has a slight amine-like odor, and has a slight,
saline taste.
Bethanechol Chloride is very soluble in water, freely soluble in glacial acetic acid, and sparingly soluble in dehydrated ethanol.
Bethanechol Chloride is hygroscopic.
A solution of Bethanechol Chloride (1 in 10) shows no
optical rotation.
Identification (1) To 2 mL of a solution of Bethanechol Chloride (1 in 40), add 0.1 mL of a solution of cobaltous chloride (1 in 100), then add 0.1 mL of potassium
ferrocyanide TS: a green color is observed, and almost
entirely fades within 10 minutes.
(2) To 1 mL of a solution of Bethanechol Chloride (1
in 100), add 0.1 mL of iodine TS: a brown precipitate is
produced, and the solution shows a greenish brown color.
(3) Determine the infrared spectra of Bethanechol
Chloride and Bethanechol Chloride RS as directed in the
paste method under the Infrared Spectrophotometry: both
same wavenumbers.
(4) A solution of Bethanechol Chloride (1 in 100) responds to the Qualitative Tests for chloride.
Melting Point About 217 C or about 221 C (after
drying)
Purity (1) Heavy metalsProceed with 1.0 g of Bethanechol Chloride according to Method 1 and perform
(2) Related substancesDissolve 1.0 g of Bethanechol Chloride in 2.5 mL of water, and use this solution as
the test solution. Pipet 1 mL of the test solution, add water to make exactly 100 mL, and use this solution as the
standard solution. Perform the test with these solutions as
directed under the Thin-layer Chromatography. Spot 1

a plate of cellulose for thin-layer chromatography. Develop the plate with a mixture of a solution of ammonium chloride acetate (1 in 100), acetone, 1-butanol and
formic acid (20:20:20:1) to a distance of about 10 cm,
o
and dry the plate at 105 C for 15 minutes. Spray evenly hydrogen hexachloroplatinate (IV)-potassium iodide
TS on the plate, and allow to stand for 30 minutes: the
spot other than the principal spot from the test solution is
not more than intense than the spot from the standard solution.
hours).
Assay Weigh accurately 0.4 g of Bethanechol Chloride,
add 40 mL of acetic anhydride, and titrate with 0.1 mol/L
Detection Method in Titrimetry). Perform a blank determination, and make any necessary correction.
= 19.668 mg of C7H17ClN2O2
Bezafibrate
O
O
H3C
CO2H
CH3
N
H
Cl
C19H20ClNO4 : 361.82
Bezafibrate contains not less than 98.5% and not more
than 101.0% of bezafibrate (C19H20ClNO4), calculated on
the dried basis.
Description Bezafibrate is a white, crystalline powder.
Bezafibrate is freely soluble in dimethylformamide, soluble in methanol, slightly soluble in dehydrated ethanol,
and practically insoluble in water.
the solutions of Bezafibrate and Bezafibrate RS in methanol (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared absorption spectra of Bezafibrate and Bezafibrate RS as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorp-
KP 9 117
tion at the same wavenumbers.
(3) Perform the test with Bezafibrate as directed under the Flame Coloration Test (2): it shows a green color.
Melting Point
Purity (1) ChloridesDissolve 3.0 g of Bezafibrate in

15 mL of dimethylformamide, dilute with water to 60
mL, shake well, allow to stand for at least 12 hours, and
filter. To 40 mL of the filtrate, add 6 mL of dilute nitric
acid and water to make 50 mL, and use this solution as
the test solution. Separately, mix 0.70 mL of 0.01 mol/L
hydrochloric acid, 10 mL of dimethylformamide, and 6
mL of dilute nitric acid. Dilute this solution with water to
50 mL, and use this solution as the control solution (not
more than 0.012%).
(2) Heavy metalsProceed with 2.0 g of Bezafibrate,
(3) Related substancesDissolve 0.1 g of Bezafibrate in 35 mL of methanol, add diluted 0.5 mol/L ammonium acetate TS (1 in 50) to make 50 mL, and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add 70 mL of methanol and diluted 0.5 mol/L ammonium acetate TS (1 in 50) to make exactly 100 mL,
the test with 5 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and determine
areas of the peaks having the relative retention times of
about 0.65 and 1.86 with respect to bezafibrate obtained
from the test solution are not larger than 0.5 times the
peak area of bezafibrate from the standard solution; the
area of the peak other than those and other than bezafibrate from the test solution is not larger than 0.2 times
the peak area of bezafibrate from the standard solution;
and the sum of the total area of the peaks other than the
peak of bezafibrate from the test solution is not larger
than 0.75 times the peak area of bezafibrate from the
standard solution.
about 25 C.
Mobile phase: A mixture of methanol and diluted dehydrated acetic acid (1 in 100) (9:4).
time of bezafibrate is about 6 minutes.
System suitability
Test for required detectability: Measure exactly 5
mL of the standard solution, and add a mixture of metha-
nol and diluted 0.5 mol/L ammonium acetate TS (1 in

50) (7 : 3) to make exactly 50 mL. Confirm that the peak
area of bezafibrate obtained with 5 L of this solution is
equivalent to 7 to 13% of that with 5 L of the standard
solution.
System performance: Dissolve 20 mg of Bezafibrate and 10 mg of 4-chlorobenzoate in 70 mL of methanol, and add diluted 0.5 mol/L ammonium acetate TS (1
in 50) to make exactly 100 mL. When the procedure is
run with 5 L of this solution under the above operating
conditions, 4-chlorobenzoate and bezafibrate are eluted
in this order with the resolution between these peaks being not less than 3.
the peak area of bezafibrate is not more than 2.0%.
Time span of measurement: About 2.5 times as
long as the retention time of bezafibrate beginning after
the solvent peak.
hours).
Assay Accurately weigh about 0.7 g of Bezafibrate,
previously dried, dissolve in 50 mL of dehydrated ethanol, and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Perform a blank
determination in the same manner and make any necessary correction.
Bifonazole
H
C
N
and enantiomer
C22H18N2: 310.39
Bifonazole, when dried, contains not less than 98.5% and
not more than 101.0% of bifonazole (C22Hl8N2).
Description Bifonazole is a white to pale yellow
Bifonazole is freely soluble in dichloromethane, soluble
in methanol, sparingly soluble in ethanol, slightly soluble
in ether and practically insoluble in water.

A solution of Bifonazole in methanol (1 in 100) does not
show optical rotation.
the solutions of Bifonazole and Bifonazole RS in methanol (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Bifonazole and
Bifonazole RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Melting Point Between 147 C and 151 C
Purity (1) ChlorideTo 2.0 g of Bifonazole add 40
mL of water, warm for 5 minutes, cool and filter. To 10
mL of the filtrate, add 6 mL of dilute nitric acid and water to make 50 mL, Perform the test using this solution as
0.021%).
0.005 mol/L sulfuric acid VS (0.048%).
(3) Heavy metalsProceed with 2.0 g of Bifonazole
(4) Related substancesPerform this test without
exposure to daylight, using light-resistant vessels. Dissolve 0.10 g of Bifonazole in 10 mL of methanol and use
this solution as the test solution. Pipet 3 mL of the test
solution and add methanol to make exactly 100 mL. Pipet 25 mL and 5 mL of this solution, add methanol to
make exactly 50 mL each and use these solutions as the
standard solutions (1) and (2), respectively. Perform the
test with the test solution and the standard solutions (1)
and (2) as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution and the standard solutions (1) and (2) on a plate of silica gel with fluorescent
plate with a mixture of ethyl acetate and strong ammonia
water (49 : 1) to a distance of about 10 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot with Rf value of about 0.20
from the test solution is not more intense than the spot
from the standard solution (1). And the spots other than
the spot mentioned above and the principal spot from the
test solution are not more intense than the spot from the
P2O5, 2 hours).

Assay Weigh accurately 0.15 g of Bifonazole, previously dried and dissolve in dichloromethane to make
exactly 50 mL. Pipet 5 mL of this solution in a glassstoppered Erlenmeyer flask, add 10 mL of water, 5 mL of
dilute sulfuric acid and 25 mL of dichloromethane and
add 2 to 3 drops of a solution of methyl yellow in dichloromethane (1 in 500) as indicator and titrate, while shaking vigorously, with 0.01 mol/L sodium lauryl sulfate VS
by a buret with 0.02-mL minimum graduation. The end
point is reached when the color of the dichloromethane
layer changes from yellow to orange-red after dropwise
addition of 0.01 mol/L sodium lauryl sulfate VS, strong
shaking and standing for a while.
Each mL of 0.01 mol/L sodium lauryl sulfate VS
= 3.1039 mg of C22Hl8N2
tight containers.
Biperidene Hydrochloride
CH2CH2C
OH
HCl
and enantiomer
C21H29NOHCl: 347.92
Biperiden Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of biperiden hydrochloride (C21H29NOHCl).
Description Biperiden Hydrochloride is a white to
brownish and yellowish white, crystalline powder.
Biperiden Hydrochloride is freely soluble in formic acid,
slightly soluble in methanol or in ethanol and practically
insoluble in ether..
o
Identification (1) Dissolve 20 mg of Biperiden Hydrochloride in 5 mL of phosphoric acid: a green color is

observed.
(2) Dissolve 10 mg of Biperiden Hydro-chloride in 5
mL of water by heating, cool and add 5 to 6 drops of
bromine TS: a yellow precipitate is produced.
of Biperiden Hydrochloride and Biperiden Hydrochloride RS (1 in 2000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
KP 9 119
(4) Determine the infrared spectra of Biperiden Hydrochloride and Biperiden Hydrochloride RS, previously
(5) Dissolve 20 mg of Biperiden Hydrochloride in 10
mL of water by heating and cool: the solution responds
to the Qualitative Tests for chloride.
Purity (1) Acid or alkaliTo 1.0 g of Biperiden Hydrochloride, add 50 mL of water, shake vigorously, filter
and to 20 mL of the filtrate, add 1 drop of methyl red TS:
no red to yellow color is observed.
(2) Heavy metalsProceed with 1.0 g of Biperiden
Biperiden Hydrochloride according to Method 3 and perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.10 g of Biperiden Hydrochloride in 20 mL of methanol and use this solution as the test solution. Pipet 1 mL of the test solution,
add methanol to make exactly 200 mL and use this solution as the standard solution. Perform the test with the
the Thin-layer Chromatography. Spot 50 L each of the
test solution and the standard solution on a plate of silica
gel for thin-layer chromatography. Develop the plate
with a mixture of chloroform, methanol and strong ammonia water (80 : 15 : 2) to a distance of about 15 cm
and air-dry the plate. Spray evenly Dragendorffs TS on
the plate: the spots other than the principal spot from the
standard solution.
hours).
Assay Weigh accurately 0.4 g of Biperiden Hydrochloride, previously dried and dissolve in 5 mL of formic acid, add 60 mL of acetic anhydride and titrate with 0.1
mol/L perchloric acid VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform a blank
= 34.792 mg of C21H29NOHCl
Bisacodyl
N
O
H3C
O
O
CH
CH3
C22H19NO4: 361.39
Bisacodyl, when dried, contains not less than 98.5% and
not more than 101.0% of bisacodyl (C22H19NO4).
Description Bisacodyl is a white, crystalline powder.
Bisacodyl is freely soluble in glacial acetic acid, soluble
in acetone, slightly soluble in ethanol or in ether and
practically insoluble in water.
Bisacodyl dissolves in dilute hydrochloric acid.
the solutions of Bisacodyl and Bisacodyl RS in ethanol
(3 in 100000) as directed under the Ultraviolet-visible
(2) Determine the infrared spectra of Bisacodyl and
Bisacodyl RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Melting Point
Purity (1) ChlorideDissolve 1.0 g of Bisacodyl in

30 mL of acetone and add 6 mL of dilute nitric acid and
as the test solution. Prepare the control solution as follows: to 0.35 mL of 0.01 mol/L hydrochloric acid VS,
add 30 mL of acetone, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.012%).
(2) SulfateDissolve 1.0 g of Bisacodyl in 2 mL of
dilute hydrochloric acid and add water to make 50 mL.
0.005 mol/L sulfuric acid VS, add 2 mL of dilute hydrochloric acid and water to make 50 mL (not more than
0.017%).
(3) Heavy metalsProceed with 2.0 g of Bisacodyl
(4) Related substancesDissolve 0.20 g of Bisacodyl in 10 mL of acetone and use this solution as the
test solution. Pipet 1 mL of the test solution, add acetone
and the standard solution on a plate of silica gel with flu-

orescent indicator for thin-layer chromatography, Develop the plate with a mixture of methyl ethyl ketone, chloroform and xylene (1 : 1 : 1) to a distance of about 10 cm
(main wavelength: 254 nm): the spots other than the
hours).
Assay Weigh accurately 0.5 g of Bisacodyl, previously
dried, dissolve in 50 mL of glacial acetic acid and titrate
with 0.1 mol/L perchloric acid VS until the color of the
solution changes from orange-yellow to green (indicator:
0.5 mL of -naphtholbenzeine TS). Perform a blank determination and make any necessary correction.
= 36.139 mg of C22H19NO4.
Bisacodyl Suppositories
Bisacodyl Suppositories contain not less than 90.0% and
not more than 110.0% of the labeled amount of bisacodyl
(C22H19NO4: 361.39).
Suppositories, with Bisacodyl.
Identification (1) To a portion of Bisacodyl Suppositories, equivalent to 6 mg of Bisacodyl according to the labeled amount, add 20 mL of ethanol, warm in a waterbath for 10 minutes, shake vigorously for 10 minutes and
allow to stand in ice-water for 1 hour. Collect the supernatant after centrifugation, filter the supernatant and to 2
mL of the filtrate, add ethanol to make 20 mL. Determine
the absorption spectrum of the solution as directed under
the Ultraviolet-visible Spectrophotometry: it exhibits a
maximum between 261 nm and 265 nm.
(2) Use the filtrate obtained in (1) as the test solution,
Separately, dissolve 6 mg of Bisacodyl RS in 20 mL of
ethanol and use this solution as the standard solution.
for thin-layer chromatography. Develop the plate with a
mixture of methyl ethyl ketone, chloroform and xylene
(1 : 1 : 1) to a distance of about 10 cm and air-dry the
254 nm): the spot from the test solution and the standard
solution show the same Rf value.

Assay Weigh accurately not less than 20 Bisacodyl
Suppositories, make fine fragments carefully and mix
uniformly. Weigh accurately a portion of the fragments,
equivalent to about 10 mg of bisacodyl (C22H19NO4), add
40 mL of tetrahydrofuran, warm to 40 C, dissolve by
shaking, cool and add tetrahydrofuran to make exactly 50
mL. Pipet 5 mL of this solution, add exactly 5 mL of the
internal standard solution and add the mobile phase to
make 100 mL. Cool this solution in ice for 30 minutes,
centrifuge, filter the supernatant liquid through a membrane filter with pore size of 0.5 m, discard the first 10
mL of the filtrate and use the subsequent filtrate as the
of Bisacodyl RS, previously dried at 105 C for 2 hours
and dissolve in tetrahydrofuran to make exactly 50 mL.
Pipet 5 mL of this solution, proceed in the same manner
as the test solution and use this solution as the standard
solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of the
peak area of bisacodyl to that of the internal standard, for
Amount (mg) of bisacodyl (C22H19NO4)
= amount (mg) of Bisacodyl RS
QT
QS
Internal standard solutionA solution of ethyl parahydroxybenzoate in acetonitrile (3 in 100000).

Mobile phase: A mixture of 0.01 mol/L citric acid TS,
acetonitrile and methanol (2 : 1 : 1).
time of bisacodyl is about 8 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, the internal standard and bisacodyl
above operating conditions, the relative standard devia-
KP 9 121
tion of the ratios of the peak area of bisacodyl to that of
Bisacodyl Tablets
Bisacodyl Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of bisacodyl
(C22H19NO4: 361.39).
Bisacodyl Tablets are enteric coated.
Method of Preparation Prepare as directed under Tablets, with Bisacodyl.
Identification To a quantity of powdered Bisacodyl
Tablets, equivalent to about 0.3 g of Bisacodyl according
to the labeled amount, add 100 mL of acetone, shake,
heat in a water-bath to boiling, filter and evaporate to
about 20 mL. Add 200 mL of water, evaporate acetone in
a water-bath, under the nitrogen gas. Cool, filter with
glass filtrator (G4) after 30 minutes and discard the filtrate. Dissolve the residue with 50 mL of acetone, evaporate to about 15 mL, add about 75 mL of water, heat in a
water-bath for 15 minutes and cool. Crystallize by scratching the wall of beaker, filter, dry at 105 C for about 15
minutes and proceed the test with the residue as directed
under Identification (2) of Bisacodyl.
Disintegration Test When the procedure is run as directed for the enteric coated tablets, the tablets do not
disintegrated after 60 minutes in the first fluid, but then
disintegrated within 45 minutes in the second fluid.
Assay Weigh accurately not less than 20 Bisacodyl
Tablets and powder. Weigh accurately a portion of the
powder, equivalent to about 25 mg of bisacodyl
(C22H19NO4), add 10 mL of water, shake thoroughly for
15 minutes and shake vigorously for 15 minutes, add 30
mL of acetonitrile, shake for 15 minutes and shake vigorously for 15 minutes, add acetonitrile to make 50 mL,
mix and filter. Discard the first 10 mL of the filtrate and
exactly take the subsequent 5 mL of the filtrate. Add exactly 5 mL of the internal standard. Use the this solution
as the test solution. Separately, Bisacodyl RS, dried at
105 C for 2 hours, weigh accurately 25 mg, and add acetonitrile to make exactly 50 mL. Take exactly 5 mL of
this solution, and treat as directed to prepare the test solution. Use this solution as the standard solution. Perform
the test with each 20 L of the test solution and the standard solution, as directed under the Liquid Chromatography according to the following conditions and calculate
the ratios, QT and Q S of the peak area of Biscodyl to
that of the internal standard for the test solution and

Amount (mg) of bisacodyl (C22H19NO4)
Q
= amount (mg) of Bisacodyl RS T
QS
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography the
particle size is 5 to 10 m.
Mobile phase: 55 mL of 0.074 mol/L sodium acetate
solution, adjust pH 7.4 with 2.5 vol% acetic acid, add 45
mL of acetonitrile.
System suitability
Packaging and Storage Preserve in well-closed containers (under 30 C).
Bismuth Subgallate
Dermatol
Bismuth Subgallate, when dried, contains not less than
47.0% and not more than 51.0% of bismuth (Bi: 208.98).
Description Bismuth Subgallate is a yellow powder, is
Bismuth Subgallate is practically insoluble in water, in
Bismuth Subgallate dissolves in dilute hydrochloric acid,
in dilute nitric acid or in dilute sulfuric acid on warming.
Bismuth Subgallate dissolves in sodium hydroxide TS,
forming a clear, yellow solution, which turns red immediately.
Bismuth Subgallate is affected by light.
Identification (1) Ignite 0.5 g of Bismuth Subgallate:
it chars at first and leaves finally a yellow residue. The
residue responds to the Qualitative Tests for bismuth salt.
(2) To 0.5 g of Bismuth Subgallate, add 25 mL of water and 20 mL of hydrogen sulfide TS and shake well.
Filter off the blackish brown precipitate and add 1 drop
of ferric chloride TS to the filtrate: a blue-black color is
produced.
Purity (1) Clarity of solution Dissolve 1.0 g of
Bismuth Subgallate in 40 mL of diluted sodium hydrox-

ide TS (1 in 8): the solution is clear.
(2) SulfateIgnite 3.0 g of Bismuth Subgallate in a
porcelain crucible and cautiously dissolve the residue in
2.5 mL of nitric acid by warming. Pour the solution into
100 mL of water, shake and filter. Evaporate 50 mL of
the filtrate in a water-bath to 15 mL. Add water to make
20 mL, filter again and use the filtrate as the test solution.
To 5 mL of the test solution, add 2 to 3 drops of barium
nitrate TS: no turbidity is produced.
(3) NitrateTo 0.5 g of Bismuth Subgallate, add 5
mL of dilute sulfuric acid and 25 mL of ferrous sulfate
TS, shake well and filter. Superimpose carefully 5 mL of
the filtrate on sulfuric acid: no red-brown color develops
at the zone of contact.
(4) AmmoniumDissolve 1.0 g of Bismuth Subgallate in 5 mL of sodium hydroxide TS and heat: the gas
evolved does not change moistened red litmus paper to
blue.
(5) CopperTo 5 mL of the test solution obtained in
(2), add 1 mL of ammonia TS and filter: no blue color
develops in the filtrate.
(6) LeadIgnite 1.0 g of Bismuth Subgallate at
o
about 500 C in a porcelain crucible, dissolve the residue in a smallest possible amount of nitric acid added
drop-wise, evaporate over a low flame to dryness and
cool. Add 5 mL of a solution of potassium hydroxide (1
in 6) to the residue, boil carefully for 2 minutes, cool and
centrifuge. Take the supernatant liquid in a test tube, add
10 drops of potassium chromate TS and acidify the solution by adding glacial acctic acid drop-wise: neither turbidity nor a yellow precipitate is produced.
(7) SilverTo 5 mL of the test solution obtained in
(2), add 0.5 mL of nitric acid and 2 to 3 drops of dilute
hydrochloric acid: no turbidity is produced.
(8) Alkaline earth metals and alkali metalsBoil
1.0 g of Bismuth Subgallate with 40 mL of diluted acetic
acid (1 in 2) for 2 minutes, cool, add water to make 40
mL and filter. To 20 mL of the filtrate, add 2 mL of dilute
hydrochloric acid, boil, immediately pass hydrogen sulfide thoroughly through the solution, filter the precipitate
produced and wash with water. Combine the filtrate and
the washings, add 5 drops of sulfuric acid and evaporate
to dryness. Ignite as directed under the Residue on Ignition: the weight of the residue does not more than 5.0 mg.
(9) ArsenicMix well 0.20 g of Bismuth Subgallate
with 0.20 g of calcium hydroxide and ignite the mixture.
Dissolve the residue in 5 mL of dilute hydrochloric acid,
use this solution as the test solution and perform the test
(10) Gallic acidTo 1.0 g of Bismuth Subgallate,
add 20 mL of ethanol, shake for 1 minute and filter. Evaporate the filtrate in a water-bath to dryness: the weight
of the residue does not more than 5.0 mg.
hours).
Assay Weigh accurately 0.5 g of Bismuth Subgallate,
previously dried, ignite at about 500 C for 30 minutes

and cool. Dissolve the residue in 5 mL of diluted nitric
acid (2 in 5) by warming and add water to make exactly
100 mL. Measure exactly 30 mL of this solution, add 200
mL of water and titrate with 0.02 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution
changes from red-purple to yellow (indicator: 2 to 3
drops of xylenol orange TS).
Each mL of 0.02 mol/L disodium ethylenediaminetetraacetate VS = 4.180 mg of Bi
preserve in light-resistant,
Bismuth Subnitrate
Bismuth Subnitrate, when dried, contains not less than
71.5% and not more than 74.5% of bismuth (Bi: 208.98).
Description Bismuth Subnitrate is a white powder.
Bismuth Subnitrate is practically insoluble in water, in
Bismuth Subnitrate readily dissolves in hydrochloric acid
or nitric acid without effervescence.
Bismuth Subnitrate is slightly hygroscopic and changes
moistened blue litmus paper to red.
Identification Bismuth Subnitrate responds to the
Qualitative Tests for bismuth salt and for nitrate.
Purity (1) ChlorideDissolve 0.7 g of Bismuth Subnitrate in 2 mL of water and 2 mL of nitric acid and add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: evaporate 2 mL of
nitric acid on a water-bath to dryness, add 0.70 mL of
0.01 mol/L hydrochloric acid VS, 6 mL of dilute nitric
(2) SulfateDissolve 3.0 g of Bismuth Subnitrate in
3.0 mL of warmed nitric acid, pour this solution into 100
mL of water and shake. Concentrate the filtrate in a water-bath to 30 mL, filter and use this filtrate as the test solution. To 5 mL of the test solution, add 2 to 3 drops of
barium nitrate TS: no turbidity is produced.
(3) AmmoniumBoil 0.10 g of Bismuth Subnitrate
with 5 mL of sodium hydroxide TS: the gas evolved does
not change moistened red litmus paper to blue.
(4) CopperTo 5 mL of the test solution obtained in
(2), add 2 mL of ammonia TS and filter: no blue color
develops.
(5) LeadTo 1.0 g of Bismuth Subnitrate, add 5 mL
of a solution of sodium hydroxide (1 in 6), boil carefully
for 2 minutes, cool and centrifuge. Transfer the supernatant liquid to a test tube, add 10 drops of potassium
chromate TS and add drop-wise acetic acid to render the
KP 9 123
solution acid: no turbidity or yellow precipitate is produced.
(6) SilverTo 5 mL of the test solution obtained in
(2), add 0.5 mL of nitric acid and 2 to 3 drops of dilute
hydrochloric acid: no turbidity is produced.
(7) Alkaline earth metals and alkali metals Boil
2.0 g of Bismuth Subnitrate with 40 mL of diluted acetic
acid (1 in 2) for 2 minutes, cool, add water to make 40
mL and filter. To 20 mL of the filtrate, add 2 mL of dilute
hydrochloric acid, boil, immediately pass hydrogen sulfide thoroughly through the solution, filter and wash the
residue with water. Combine the filtrate and the washings,
add 5 drops of sulfuric acid, evaporate to dryness and ignite as directed under the Residue on Ignition: the residue does not exceed 5.0 mg.
(8) ArsenicTo 0.20 g of Bismuth Subnitrate, add 2
mL of sulfuric acid, heat until white fumes evolve, dilute
cautiously with water to make 5 mL, use this solution as
the test solution and perform the test (not more than 10
ppm).
hours).
Assay Weigh accurately 0.4 g of Bismuth Subnitrate,
previously dried, dissolve in 5 mL of diluted nitric acid
(2 in 5) by warming and add water to make exactly 100
mL. Pipet 25 mL of the solution, add 200 mL of water
and titrate with 0.02 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution changes from
red-purple to yellow (indicator: 5 drops of xylenol
orange TS).
Each mL of 0.02 mol/L disodium ethylenediaminetetraacetate VS = 4.180 mg of Bi
Bisoprolol Fumarate

D : Between 2 and
+0.2 (0.2 g, methanol 20 mL, 100 mm)
Purity (1) Heavy metalsProceed with 1.0 g of Bisoprolol Fumarate according to Method 1 and perform the
(2) Fumaric acidDissolve about 0.5 g of Bisoprolol Fumarate, accurately weighed, in 70 mL of dehydrated alcohol. Add 8.0 mL of 0.1 mol/L tetrabutylammonium hydroxide VS, stir for 2 minutes, and titrate
with 0.1 mol/L tetrabutylammonium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any
necessary correction. Not less than 14.8% and not more
than 15.4% of fumaric acid is found, calculated on the
anhydrous basis.
Each mL of 0.1 mol/L tetrabutylammonium hydroxide
VS = 5.804 mg of fumaric acid (C4H4O4)
(3) Related substances Prepare the test solution as
directed in the Assay. Perform the test with 10 L of the
test solution as directed under the Liquid Chromatography according to the procedure in the Assay, and measure peak areas. When the percentage of total related substances in the portion of Bisoprolol Fumarate is calculated, not more than 0.5% of total related substances is
found.
COOH
H
N
CH3
Ai
AS
CH3
H3C

spectra of Bisoprolol Fumarate and Bisoprolol Fumarate
RS as directed in the potassium bromide disk method
(2) The retention time of the principal peak from the
test solution corresponds to that from the standard solution, as obtained in the Assay.
Amount (%) of total related substances = 100
OH
O
ethyl acetate.
CH3
HOOC
O
2
(C18H31NO4)2C4H4O4 : 766.96
Bisoprolol Fumarate contains not less than 97.5% and
not more than 102.0% of bisoprolol fumarate
(C18H31NO4)2C4H4O4, calculated on the anhydrous basis.
Description Bisoprolol Fumarate is a white crystalline
powder.
Bisoprolol Fumarate is very soluble in water or in methanol, freely soluble in ethanol, in glacial acetic acid or
in chloroform, and sparingly soluble in acetone or in
Ai is the sum of all the peak areas, excluding the

peak areas of fumaric acid and bisoprolol.
AS is the sum of all the peak areas in the chromatograpm.
Water Not more than 0.5%. (1 g, volumetric titration,

direct titration).
Assay Dissolve 50 mg of Bisoprolol Fumarate, accurately weighed, in a mixture of acetonitrile and water
(35:65) to make exactly 50 mL, and use this solution as

the test solution. Separately, weigh accurately about 50
mg of Bisoprolol Fumarate RS, dissolve in 35% acetonitrile solution to make exactly 50 mL, and use this solution as the standard solution. Perform the test with 10 L
the following conditions, and determine the peak areas,
AT and AS , of Bisoprolol Fumarate.
Bleomycin Sulfate
NH2
H
N
NH2
NH2
R
N
N
CH3
H
H
O
H2N
N
H
CH3
CH3
N
O
N
H
O
OH
Preserve in tight, light-
HO
N
H
OH
AS

resistant containers.
[(C18H31NO4)2C4H4O4] = 50 C AT
Column: A stainless steel column about 4.6 mm inside diameter and 12.5 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 10
Mobile phase: To 1000 mL of 35% acetonitrile solution, add 5 mL of heptafluorobutyric acid, 5 mL of diethylamine, and 2.5 mL of formic acid, mix, and filter.
System suitability
System performance: Dissolve 25.0 mg of propranolol hydrochloride and 50.0 mg of Bisoprolol Fumarate
in 35% acetonitrile solution to make 50 mL. When the
procedure is run with 10 L of this solution as directed in
the Liquid chromatography under the above operating
conditions, the resolution between the peaks of bisoprolol and propranolol is not less than 7.0. When the procedure is run with 10 L of the standard solution, the
symmetry factor is not more than 2.0.
above operating conditions, the relative standard deviation of the peak area of bisoprolol is not more than 2.0%.
HN
Amount (mg) of bisoprolol fumarate
O
H
HO
O
CH3
C : the concentration (mg/mL) of Bisoprolol Fumarate

RS in the standard solution.
H
N
OH
x H2SO4
OH
OH O
O
O
NH2
OH
Bleomycin acid: R = OH
Bleomycin A1: R = NHCH2CH2CH2SOCH3
Bleomycin dimethyl: A2 R = NHCH2CH2CH2SCH3
CH3
Bleomycin A2: R = NHCH2CH2CH2S+
XCH3
Bleomycin A2'-a: R = NHCH2CH2CH2CH2NH2
Bleomycin A2'-b: R = NHCH2CH2CH2NH2
Bleomycin A5: R = NH(CH2)3NH(CH2)4NH2
Bleomycin B1: R = NH2
Bleomycin B2: R = NH(CH2)4NHC(NH)NH2
Bleomycin B4:
R= NH(CH2)4NHC(NH)NH(CH2)4NHC(NH)NH2
Bleomycin Sulfate is the sulfate of a mixture of substances having antitumor activity produced by the growth
of Streptomyces verticillus.
Bleomycin Sulfate contains not less than 1400 g (potency) and not more than 2000 g (potency) per mg of
bleomycin A2 (C55H84ClN17O21S3: 1451.01), calculated
on the dried basis.
Description Bleomycin Sulfate is a white to yellowish
white powder.
Bleomycin Sulfate is freely soluble in water, slightly soluble in ethanol, and practically insoluble in ether.
Identification (1) Weigh 10 mg of Bleomycin Sulfate,
dissolve in 2 mL of water, and add barium chloride TS to
this solution; a white precipitate develops. This precipitate does not dissolve in diluted nitric acid, but dissolve
in excess ammonia TS.
(2) Weigh 4 mg of Bleomycin Sulfate, add 5 L of
copper sulfate TS and water to make 100 mL. Determine
the absorption spectrum of this solution as directed under
Ultraviolet-visible Spectrophotometry, it exhibits maxima between 240 nm and 243 nm, and between 288 nm
and 293 nm, and minimum between 267 nm and 270 nm.
pH The pH of a solution obtained by dissolving 50
mg of Bleomycin Sulfate in 10 mL of water is between
4.5 and 6.0.
KP 9 125
Purity Content of copper Weigh accurately about 15

mg of Bleomycin Sulfate, dissolve in diluted hydrochloric acid (1 in 100), make exactly 10 mL, and use this solution as the test solution. Pipet exactly 10 mL each of the
test solution and the copper standard solution, add 10 mL
of zinc dibenzyldithiocarbamate TS, shake vigorously for
one minute, allow to stand to separate the layers, take the
lower layer, if necessary, add 1 g of anhydrous sodium
sulfate, shake to dehydrate and filter. Separately, make a
blank solution with the same manner except the addition
of copper standard solution. Determine the absorbance of
the test solution, the standard solution and the blank solution at 435 nm, AT , AS and AO , as directed under
Ultraviolet-visible Spectrophotometry, and calculate the
content of copper according to the following equation
(not more than 0.02 %).
Amount [%] of copper
=
1.5 ( AT - AO )
Amount (mg) of the sample taken ( AS - AO )
Sterility Test It meets the requirement, when Bleomycin Sulfate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Bleomycin Sulfate is used in a sterile preparation. Weigh appropriate amount of Bleomycin Sulfate, dissolve in water,
make the solution so that each mL contains 200 g, and
of rabbit.
Histamine It meets the requirement, when Bleomycin
Sulfate is used in a sterile preparation. Weigh appropriate
amount of Bleomycin Sulfate, dissolve in water, make
the solution so that each mL contains 300 g, and use the
solution as the test solution.
Loss on Drying Not more than 3.0 % (50 mg, in vacuum, 60 C, 3 hours).
Content Ratio of Bleomycin Weigh accurately 10 mg
(potency) of Bleomycin Sulfate, dissolve in 20 mL of
water, and use this solution as the test solution. Perform
operating conditions, and determine each peak area.
Based on the % of peak area, bleomycin A2 (the first
principal peak) is between 55 % and 70 %, bleomycin B2
(the second principal peak) is between 25 % and 32 %,
the total peak area of bleomycin A2 and bleomycin B2 is
not less than 85 %, the peak area of dimethylbleomycin
A2 ( a peak having the relative retention time of 1.5 ~ 2.5
against bleomycin A2) is not more than 5.5 %, and the total area of the rest peaks is not more than 9.5 %.

about 40 C
Mobile phase A : A mixture of the mobile phase stock
solution and methanol (9:1)
Mobile phase B : A mixture of the mobile phase stock
solution and methanol (3:2)
Time ( min)
Mobile phase A
(vol %)
Mobile phase B
(vol %)
0 ~ 60
100 0
0 100
60 ~ 75
100
Flow rate: About1.2 mL per min

System suitability
with 20 L of the test solution under the above operating
conditions, bleomycin A2 and bleomycin B2 are eluted in
this order with the resolution between these peaks being
not less than 5.
times with 20 L of the test solution under the above operating conditions, the relative standard deviation of the
each peak area is not more than 2.0 %.
Mobile phase stock solution: Dissolve 0.96 g of
sodium 1-pentanesulfonate and 1.86 g of disodium dihydrogen ethylenediamine tetraacetate dehydrate in 1000
mL of water and 5 mL of glacial acetic acid, and adjust
the pH to 4.3 with ammonia TS.
Time span of measurement: Twenty minutes after elution
of the peak of demethylbleomycin A2 beginning after the
solvent peak.
for seed and base layerPeptone
10.0 g
Glycerine
10.0 g
Meat extract
10.0 g
Agar
15.0 20.0 g
Sodium chloride 1.5 g
Water
1000 mL
Mix all the ingredients, and sterilize. Adjust the pH of
the solution so that it will be 6.9 to 7.1 after sterilization.
(2) Liquid media for suspending the test organism
Peptone
10.0 g Sodium chloride
3.0 g
Meat extract
10.0 g Glycerine
10.0 g
Water
1000 mL
Mix all the ingredients, and sterilize. Adjust the pH
of the solution so that it will be 6.9 to 7.1 after sterilization.
(3) Test organism - Mycobacterium smegmatis ATCC
607.
(4) Preparation of seeded agar layer Cultivate the

test organism, on the slant of the agar medium for transferring the test organism at 27 C for 40 to 48 hours, then
inoculate the test organism thus obtained in 100 mL of
the liquid media for suspending the test organism, cultivate with shaking at between 25 C and 27C for 5 days,
and use this as the suspension of test organism. Store the
suspension of test organism at a temperature not exceeding 5 C, and use within 14 days. Add 0.5 mL of the suspension of test organism in 100 mL of the agar medium
for seed previously kept at 48 C, mix thoroughly, and
use as the seeded agar layer.
(5) Agar plate Proceed as directed in I 5 under the
Microbial Assay for Antibiotics. Use 5.0 mL of agar medium for base layer and 8.0 mL of the agar medium for
seed.
(6) Weigh accurately about 5 mg (potency) of Bleomycin Sulfate, dissolve in 0.1 mol/L phosphate buffer solution, pH 6.8 to make the solutions so that each mL contains 30.0 g (potency) and 15.0 g (potency), and use
these solutions as the high concentration test solution and
the low concentration test solution. Separately, weigh accurately an amount of Bleomycin Hydrochloride RS,
previously dried, equivalent to about 5 mg (potency) and
dissolve in 0.1 mol/L phosphate buffer solution, pH 6.8
to make the solution so that each mL contains 150.0 g
(potency) and use the solution as the standard stock solution. Keep the standard solution at not exceeding 5 C
and use within 30 days. Take exactly a suitable amount
of the standard stock solution, add 0.1 mol/L phosphate
contains 30.0 g (potency) and 15.0 g (potency), and
use these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under
Microbial Assay for Antibiotics.
sponds to the Qualitative Tests for borate.

1.0 g of Boric acid in 25 mL of water or in 10 mL of hot
ethanol: the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Boric Acid
Boric Acid according to Method 1 and perform the test
hours).
Assay Weigh accurately 1.5 g of Boric Acid, previously dried, add 15 g of D-Sorbitol and 50 mL of water, ant
dissolve by warming. After cooling, titrate with 1 mol/L
sodium hydroxide VS (indicator: 2 drops of phenolphthalein TS).
Each mL of 1 mol/L sodium hydroxide VS
= 61.83 mg of H3BO3
Bromazepam
O
H
N
Br
Packaging and Storage Preserve in tight containers (2

~ 8 C).
Boric Acid
H3BO3: 61.83
Boric Acid, when dried, contains not less than 99.5% and
not more than 101.0% of boric acid (H3BO3).
Description Boric Acid is a colorless or white crystal
or crystalline powder, odorless and has a slight, characteristic taste.
Boric Acid is freely soluble in warm water, in hot ethanol
or in glycerin, soluble in water or in ethanol and practically insoluble in ether.
pH A solution of Boric Acid (1 in 20) is between
3.5 and 4.1.
Identification A solution of Boric acid (1 in 20) re-
C14H10BrN3O: 316.15
Bromazepam, when dried, contains not less than 99.0%
and not more than 101.0% of bromazepam
(C14H10BrN3O).
Description Bromazepam is a white to pale yellowish
white crystal or crystalline powder and is odorless. Bromazepam is freely soluble in dimethylformamide or in
glacial acetic acid, sparingly soluble in chloroform,
slightly soluble in methanol or in dehydrated ethanol,
very slightly soluble in ether and practically insoluble in
water.
Bromazepam dissolves in dilute hydrochloric acid.
the solutions of Bromazepam and Bromazepam RS in
dehydrated ethanol (1 in 200000) under the Ultraviolet-
KP 9 127
visible Spectrophotometry: both spectra exhibit similar
(2) Determine the absorption spectra of Bromazepam
and Bromazepam RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry:
the same wavelnumbers.
Purity (1) Heavy metalsProceed with 1.0 g of Bromazepam in a platinum crucible according to Method 4
and perform the test. Prepare the control solution with
2.0 mL of standard lead solution (not more than 20 ppm).
(4) Related substancesDissolve 50 mg of Bromazepam in 5 mL of a mixture of acetonitrile and methanol
(3 : 2) and use this solution as the test solution. Pipet 1
mL of the test solution and add a mixture of acetonitrile
and methanol (3 : 2) to make exactly 50 mL. Pipet 5 mL
of this solution, add a mixture of acetonitrile and methanol (3 : 2) to make exactly 50 mL and use this solution as
a fluorescent indicator for thin-layer chromatography.
Develop the plate with a mixture of ethyl acetate, dehydrated ethanol and strong ammonia water (38 : 1 : 1) to a
distance of about 12 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm): the
spots other than the principal spot from the test solution
and the spot of the starting point are not more than 2 and
not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately 0.4 g of Bromazepam, previously dried, dissolve in 80 mL of glacial acetic acid
= 31.615 mg of C14H10BrN3O
Bromhexine Hydrochloride
Br
CH3
CH2
Br
NH2
HCl
C14H20Br2N2HCl: 412.59
Bromhexine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of bromhexine (C14H20Br2N2HCl).
Description Bromhexine Hydrochloride is a white
crystal or crystalline powder, is odorless and tasteless.
Bromhexine Hydrochloride is freely soluble in formic
acid, sparingly soluble in methanol and slightly soluble
in water or ethanol and practically insoluble in ether.
pH The pH of saturated solution of Bromhexine
Hydrochloride is between 3.0 and 5.0.
Identification (1) Dissolve 3 mg each of Bromhexine
Hydrochloride and Bromhexine Hydrochloride RS in
0.01 mol/L hydrochloric acid TS to make 100 mL. Determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Bromhexine
Hydrochloride and Bromhexine Hydrochloride RS as directed in the potassium bromide disk method under the
(3) Add 20mL of water to 1 g of Brohexine Hydrochloride. After thorough shaking, add 3 mL of sodium hydroxide TS and extract with four 20 mL portions of ether.
Neutralize the water layer with dilute nitric acid: the solution responds to the Qualitatve Test (2) for chloride.
Purity (1) Heavy metalsProceed with 2.0 g of
Bromhexine Hydrochloride according to Method 2 and
exposure to daylight, using light-resistant vessels. Dissolve 50 mg of Bromhexine Hydrochloride in 10 mL of
methanol and use this solution as the test solution. Pipet
1 mL of the test solution and add the mobile phase to
make exactly 20 mL. Pipet 1 mL of this solution, add the
mobile phase to make exactly 25 mL and this solution as
the standard solution. Perform the test with 5 L each of
the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and determine each peak area by the automatic integration method: each peak area other than
bromhexine from the test solution is not larger than the
peak area of bromhexine from the standard solution.

about 40 C
Mobile phase: Dissolve 1.0 g of potassium hydrogen
phosphate in 900 mL of water, adjust the pH to 7.0 with
0.5 mol/L sodium hydroxide TS and add water to make
1000 mL. To 200 mL of this solution 800 mL of acetonitrile.
Flow rate: Adjust flow rate so that the retention time
of bromhexine is about 6 minutes.
System suitability
System performance: To 50 mg of bamethane sulfate add 0.5 mL of the test solution and add the mobile
phase to make 10 mL. When the procedure is run with 5
L of this solution under the above operating conditions,
bamethane and bromhexine are eluted in this order with
the resolution between these peaks being not less than 7.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of bromhexine from 5 L of
the standard solution is between 5 mm and 15 mm.
retention time of bromhexine after the solvent peak.
hours).
Assay Weigh accurately 0.5 g of Bromhexine Hydrochloride, previously dried, dissolve in 2 mL of formic
acid, add 60 mL of acetic anhydride and warm in a 50 C
water-bath and cool. Titrate with 0.1 mol/L perchloric acid until the color of the solution changes from purple
through blue-green to yellow-green (indicator: 2 drops of
methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.
= 41.26 mg of C14H20Br2N2HCl

Bromocriptine Mesilate
OH
O (CH3)2CH
H
H
N
O
N
H
N
O
CH2CH(CH 3)2
CH3SO 3H
CH3
H
HN
Br
C32H40BrN5O5CH4O3S: 750.70
Bromocriptine Mesilate contains not less than 98.0% and

not more than 101.0% of bromocriptine mesilate
(C32H40BrN5O5CH4O3S), calculated on the dried basis.
Description Bromocriptine Mesilate is a white to pale
yellowish white or pale brownish white, crystalline
powder and is odorless or has a faint characteristic odor.
Bromocriptine Mesilate is very soluble in glacial acetic
acid, freely soluble in methanol, sparingly soluble in
ethanol, very slightly soluble in acetic anhydride, in
dichloromethane or in chloroform and practically insoluble in water or in ether.
Bromocriptine Mesilate is gradually affected by light.
Identification (1) Dissolve 2 mg of Bromocriptine
Mesilate in 1 mL of methanol, add 2 mL of pdimethylaminobenzaldehyde-ferric chloride TS and
shake: a purplish blue color is observed.
of Bromocriptine Mesilate and Bromocriptine Mesilate
RS in methanol (3 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
similar intensities of absorptioni at the same wavelengths.
(3) Determine the infrared spectra of Bromocriptine
Mesilate and Bromocriptine Mesilate RS, previously
dried, as directed in the paste method under the Infrared
(4) Perform the test with Bromocriptine Mesilate as
directed under the Flame Coloration Test (2): a green
color is observed.
D : Between +95 and
+105 [0.1 g previously dried, a mixture of methanol and
dichloromethane (1 : 1), 10 mL, 100 mm].
Purity (1) Clarity and color of solutionDissolve
0.10 g of Bromocriptine Mesilate in 10 mL of methanol:
the solution is clear and has no more color than the following control solution.
Control solutionTo 2.5 mL of cobaltous chloride stock
CS, 6.0 mL of ferric chloride stock CS and 1.0 mL of cupric sulfate stock CS, add diluted hydrochloric acid (1 in
40) to make exactly 100 mL.
(2) Heavy metalsProceed with 1.0 g of Bromocriptine Mesilate according to Method 2 and perform the test.
exposure to daylight, using light-resistant vessels. Dissolve 0.10 g of Bromocriptine Mesilate in 10 mL of a
mixture of methanol and chloroform (1 : 1) and use this
solution as the test solution. Pipet 1 mL of the test solution, add a mixture of methanol and chloroform (1 : 1) to
make exactly 200 mL and use this solution as the standard solution (1). Pipet 10 mL of the standard solution
(1), add a mixture of methanol and chloroform (1 : 1) to
KP 9 129
solution (2). Perform the test with the test solution and
the standard solutions (1) and (2) as directed under the
solution and the standard solutions (1) and (2), as a band
with 1 cm in width, on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop
the plate immediately with a mixture of dichloromethane,
dioxane, ethanol and strong ammonia water (1800 : 150 :
50 : 1) to a distance of about 10 cm and dry the plate under reduced pressure for 30 minutes. Spray evenly Dragendorffs TS on the plate, then spray evenly hydrogen
peroxide TS, cover the plate with a glass plate and examine: the spots other than the principal spot from the
standard solution (1) and the spot other than the principal
spot, which is more intense than the spot from the standard solution (2), is not more than one.
Loss on Drying Not more than 3.0% (1 g, not exceeding 0.67 kPa, 80 C, 5 hours).
Assay Weigh accurately 0.6 g of Bromocriptine Mesilate, dissolve in 80 mL of a mixture of glacial acetic acid
and acetic anhydride (7 : 1) and titrate with 0.1 mol/L
= 75.07 mg of C32H40BrN5O5CH4O3S
tight containers. Store at a temperature below 18 C.
Bromvalerylurea
Br
(CH3)2CHC
O
C
Bromovalerylurea dissolve in sodium hydroxide TS.

Identification (1) Boil 0.2 g of Bromovalerylurea with
5 mL of a solution of sodium hydroxide (1 in 10): the gas
evolved changes moistened red litmus paper to blue. Boil
this solution with an excess of dilute sulfuric acid: the
odor of valeric acid is perceptible,
(2) To 0.1 g of Bromovalerylurea, add 0.5 g of anhydrous sodium carbonate and decompose thoroughly by
gentle heating. Dissolve the residue in 5 mL of hot water,
cool, acidify with acetic acid and filter: the filtrate responds to the Qualitative Tests (2) for bromide.
Melting Point
Purity (1) Acidity or alkalinityTo 1.5 g of Bromovalerylurea, add 30 mL of water, shake for 5 minutes and
filter: the filtrate is neutral.
(2) ChloridePerform the test with a 10 mL of the
filtrate obtained in (1). Prepare the control solution with
0.40 mL of 0.01 mol/L hydrochloric acid VS (not more
than 0.028%).
(3) SulfatePerform the test with 10 mL of the filtrate obtained in (1). Prepare the control solution with
0.40 mL of 0.005 mol/L sulfuric acid VS (not more than
0.038%).
(4) Heavy metalsProceed with 2.0 g of Bromovalerylurea according to Method 2 and perform the test.
(5) ArsenicDissolve 0.5 g of Bromovalerylurea in
5 mL of sodium hydroxide TS, use this solution as the
test solution and perform the test (not more than 4 ppm).
test with 0.5 g of Bromovalerylurea: the solution has no
more color than Color Matching Fluid A.
hours).
O
NH
NH2
and enantiomer
C6H11BrN2O2: 223.07
Bromovalerylurea, when dried, contains not less than
98.0% and not more than 101.0% of bromovalerylurea
(C6H11BrN2O2).
Description Bromovalerylurea is a white crystal or
taste.
Bromovalerylurea is soluble in ethanol, sparingly soluble
in ether and very slightly soluble in water.
Bromovalerylurea dissolves in sulfuric acid, nitric acid
or hydrochloric acid and precipitates are produced on the
addition of water.

Assay Weigh accurately 0.4 g of Bromovalerylurea,
previously dried, in an Erlenmeyer flask, add 40 mL of
sodium hydroxide TS and boil gently for 20 minutes under a reflux condenser. Cool, wash the lower part of the
reflux condenser and the mouth of the flask with 30 mL
of water and combine the washings with the solution in
the Erlenmeyer flask. Add 5 mL of nitric acid and exactly 30 mL of 0.1 mol/L silver nitrate VS and titrate the
excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ferric ammonium sulfate TS).
correction.
= 22.307 mg of C6H11BrN2O2

tainers.
Bucumolol Hydrochloride
OH
OCH2CCH2NHCH(CH3)3
H O
HCl
CH3
C17H23NO4HCl: 341.83
Bucumolol Hydrochloride, when dried, contains not less
than
99.0%
of
bucumolol
hydrochloride
(C17H23NO4HCl).
Description Bucumolol Hydrochloride is a white crystal or crystalline powder.
Bucumolol Hydrochloride is freely soluble in water, sparingly soluble in methanol or in ethanol, slightly soluble
in glacial acetic acid and practically insoluble in ether.
o

Identification (1) Dissolve 10 mg of Bucumolol Hydrochloride in 10 mL of diluted ethanol (1 in 2) and observe under ultraviolet light (main wavelength: 365 nm):
the solution has a yellow-green fluorescence. Render this
solution alkaline by adding sodium hydroxide TS: the
fluorescence disappears. Acidify the solution by adding
dilute hydrochloric acid: the fluorescence reappears.
(2) Dissolve 0.1 g of Bucumolol Hydrochloride in 5
mL of water and add 5 drops of Reinecke salt TS: a light
red precipitate is formed.
of Bucumolol Hydrochloride and Bucumolol Hydrochloride RS (1 in 60000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(4) Determine the infrared spectra of Bucumolol Hydrochloride and Bucumulol Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
(5) A solution of Bucumolol Hydrochloride (1 in 50)
%
Absorbance E11cm
(296 nm): Between 330 and 360 (after drying, 40 mg, water, 2500 mL).

g of Bucumolol Hydrochloride in 20 mL of water: the solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 1.0 g of Bucumolol

Bucumolol Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.10 g of Bucumolol Hydrochloride in 10 mL of methanol and use this solution as the test solution. Pipet 1 mL of the test solution
and add methanol to make exactly 50 mL. Pipet 5 mL of
this solution, add methanol to make exactly 25 mL and
test with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 5 L
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methanol and ammoniaammonium chloride buffer solution, pH 10.7 (30 : 1) to a
are not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately 0.4 g of Bucumolol Hydrochloride, previously dried, add 45 mL of glacial acetic acid,
dissolve by warming at 60 C and cool. Add 105 mL of
acetic anhydride and titrate with 0.1 mol/L perchloric acid VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and
= 34.183 mg of C17H23NO4.HCl
Bufetolol Hydrochloride
OH
OCH2CHCH2NHC(CH3)3
HCl
OCH2
C18H29NO4HCl: 359.89
Bufetolol Hydrochloride, when dried, contains not less
than 98.5% of bufetolol hydrochloride (C18H29NO4HCl).
KP 9 131
Description Bufetolol Hydrochloride is a white crystal
or crystalline powder.
Bufetolol Hydrochloride is freely soluble in water or in
methanol, soluble in ethanol or in glacial acetic acid and
A solution of Bufetolol Hydrochloride (1 in 10) is optically inactive.
Identification (1) To 5 mL of a solution of Bufetolol
Hydrochloride (1 in 100), add 5 drops of Reinecke salt
TS: a pale red precipitate is produced.
of Bufetolol Hydrochloride and Bufetolol Hydrochloride
RS (1 in 20000) as directed under the Ultraviolet-visible
(3) Determine the infrared spectra of Bufetolol Hydrochloride and Bufetolol Hydrochloride RS, previously
(4) A solution of Bufetolol Hydrochloride (1 in 50)
g of Bufetolol Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.5 g of Bufetolol
Hydrochloride. Prepare the control solution with 0.40
0.038%).
(3) Heavy metalsProceed with 2.0 g of Bufetolol
(4) Related substancesDissolve 0.20 g of Bufetolol Hydrochloride in 5 mL of methanol and use this solution as the test solution. Pipet 1 mL of the test solution,
gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform,
acetone, ethanol and strong ammonia water (40 : 20 : 5 :
1) to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm):
solution.
hours).
Assay Weigh accurately 0.4 g of Bufetolol Hydrochloride, previously dried, dissolve in 10 mL of glacial acetic
acid, add 50 mL of acetic anhydride and titrate with 0.1
mol/L perchloric acid VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform a blank
= 35.989 mg of C18H29NO4HCl
Bufexamac
O
CH3CH2CH2CH2O
CH2
NHOH
Cl2H17NO3: 223.27
Bufexamac, when dried, contains not less than 98.0%
and not more than 101.0% of bufexamac (Cl2H17NO3).
Description Bufexamac is a white to pale yellowish
white crystal or crystalline powder, has a faint, characteristic odor and is tasteless.
Bufexamac is freely soluble in dimethylformamide, sparingly soluble in methanol or in ethanol and practically
insoluble in water or ether.
Identification (1) To 5 mL of a solution of Bufexamac
in methanol (1 in 5000), add 1 drop of ferric chloridemethanol TS and shake: a dark red color develops.
of Bufexamac and Bufexamac RS in ethanol (1 in
100000) as directed tinder the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
(3) Determine the infrared spectra of Bufexamac and
Bufexamac RS as directed in the potassium bromide disk
same wavenumbers.
Purity (1) Clarity and color of solution Reconstitute 0.20 g of Bufexamac in 20 mL of ethanol: the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Bufexamac
Bufexamac according to Method 3 and perform the test
(4) Related substancesDissolve 0.20 g of Bufexamac in 10 mL of methanol and use this solution as the
test solution. Pipet 1 mL of the test solution, add methanol to make exactly 100 mL and use this solution as the
Chromatography. Use a plate of silica gel with fluorescent indicator for thin-layer chromato-graphy, moisten
the surface of the plate evenly by spraying with 0.1
mol/L disodium ethylene-diaminetetraacetate TS and dry
at 110 C for about 30 minutes. Spot 15 L each of the
test solution and the standard solution on the plate. Develop the plate with a mixture of chloroform, cyclohexane, methanol and glacial acetic acid (6 : 4 : 1 : 1) to a
hours).
Assay Weigh accurately about 0.2 g of Bufexamac,
hydroxide-methanol VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank
hydroxide-methanol VS = 22.327 mg of Cl2H17NO3
matography. Use a plate of silica gel for thin-layer chromatography, moisten the surface of the plate evenly by
spraying with 0.1 mol/L disodium ethylenediaminetetraacetate TS and dry the plate at 110 C for
about 30 minutes. Spot 5 L each of the test solution and
the standard solution on the plate. Develop the plate with
a mixture of pentane, ethyl acetate and glacial acetic acid
plate. Spray evenly ferric chloride TS on the plate: the
spot from the sample solution and the standard solution
show a red-brown color and the same Rf value.
Assay Weigh accurately a quantity of Bufexamac
Cream, equivalent to about 50 mg of bufexamac
(Cl2H17NO3), dissolve in 40 mL of methanol and add methanol to make exactly 50 mL. Pipet 10 mL of this solution, add exactly 5 mL of the internal standard solution
and the mobile phase to make 100 mL, filter and use the
filtrate as the test solution. Separately, weigh accurately
50 mg of Bufexamac RS, previously dried at 105 C for 4
hours and dissolve in methanol to make exactly 50 mL.
Pipet 10 mL of this solution, add exactly 5 mL of the internal standard solution, add the mobile phase to make
100 mL and use this solution as the standard solution.
calculate the ratios, QT and QS , of the peak area of
Bufexamac to that of the internal standard, for the test
Amount (mg) of bufexamac (Cl2H17NO3)
= amount (mg) of Bufexamac RS
QT
QS
Internal standard solutionA solution of diphenylimidazole in methanol (1 in 5000).
Bufexamac Cream
Bufexamac Cream contains not less 90.0% and not more
than 110.0% of the labeled amount of bufexamac
(Cl2H17NO3: 223.27).
Creams, with Bufexamac.
Prepared as directed under
Description Bufexamac Cream is white.

pH Between 4.0 and 6.0
Identification To a quantity of Bufexamac Cream,
equivalent to 50 mg of Bufexamac according to the labeled amount, add 10 mL of tetrahydrofuran, shake well,
centrifuge and use the supernatant liquid as the test solution. Separately, dissolve 50 mg of bufexamac for Assay
in 10 mL of methanol and use this solution as the standard solution. Perform the test with the test solution and
standard solution as directed under the Thin-layer Chro-
about 25 C.
Mobile phase: Dissolve 2.5 g of sodium 1octanesulfonate and 0.6 g of disodium ethylenediaminetetraacetate in 850 mL of water and add 400 mL
of methanol, 400 mL of acetonitrile and 8 mL of glacial
acetic acid.
time of Bufexamac is about 6 minutes.
System suitability
with 20 L of the standard solution under the above op-
KP 9 133
erating conditions, bufexamac and the internal standard
peaks being not less than 8
above operating conditions, the relative standard deviation of the ratios of the peak area of bufexamac to that of
tion. Perform the test with 20 L each of the test solution

and the standard solution as directed under the Liquid
and calculate the ratios, QT and QS , of the peak area
of Bufexamac to that of the internal standard, for the test
Amount (mg) of bufexamac (Cl2H17NO3)
= amount (mg) of Bufexamac RS
QT
QS
Bufexamac Ointment
Internal standard solutionA solution of diphenylimidazole in methanol (1 in 5000).
Bufexamac Ointment contains not less than 90.0% and

not more than 110.0% of the labeled amount of bufexamac (Cl2H17NO3: 223.27).
about 25 C.
Mobile phase: Dissolve 2.5 g of sodium 1octanesulfonate and 0.6 g of disodium ethylenediaminetetraacetate in 850 mL of water and add 400 mL
of methanol, 400 mL of acetonitrile and 8 mL of glacial
acetic acid.
time of Bufexamac is about 6 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, bufexamac and the internal standard
above operating conditions, the relative standard deviation of the ratios of the peak area of bufexamac to that of

Ointments, with Bufexamac.
Identification To a quantity of Bufexamac Ointment,
equivalent to 50 mg of Bufexamac according to the labeled amount, add 5 mL of tetrahydrofuran, shake well,
add 5 mL of dehydrated ethanol, shake, centrifuge and
use the supernatant liquid as the test solution. Separately,
dissolve 50 mg of Bufexamac RS 10 mL of methanol and
test with the test solution and standard solution as directed under the Thin-layer Chromatography. Use a plate
of silica gel for thin-layer chromatography, moisten the
surface of the plate evenly by spraying with 0.1 mol/L
disodium ethylenediaminetetraacetate TS and dry the
plate at 110 C for about 30 minutes. Spot 5 L each of
the test solution and the standard solution on the plate.
Develop the plate with a mixture of pentane, ethyl acetate and glacial acetic acid (7 : 4 : 1) to a distance of
about 10 cm and air-dry the plate. Spray evenly ferric
chloride TS on the plate: the spot from the test solution
and the standard solution show a red-brown color and the
same Rf value.
Assay Weigh accurately a quantity of Bufexamac
Ointment, equivalent to about 50 mg of bufexamac
(Cl2H17NO3), add 40 mL of tetrahydrofuran, warm to 40
C. dissolve by shaking, cool and add tetrahydrofuran to
exactly 5 mL of the internal standard solution and the
mobile phase to make 100 mL and filter, if necessary,
through a membrane filter of 0.45m porosity. Discard
the first 20 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, weigh accurately 50
mg of Bufexamac RS, previously dried at 105 C for 4
hours and dissolve in tetrahydrofuran to make exactly 50
mL. Pipet 10 mL of this solution, add exactly 5 mL of
the internal standard solution and the mobile phase to
make 100 mL and use this solution as the standard solu-
Buflomedil Hydrochloride
OCH3
O
N
HCl
H3 CO
OCH3
C17H25NO4HCl : 343.85
Buflomedil Hydrochloride contains not less than 98.5%
and not more than 101.5% of buflomedil hydrochloride

(C17H25NO4HCl), calculated on the dried basis.
Description Buflomedil Hydrochloride is a white,
crystalline powder.
Buflomedil Hydrochloride is freely soluble in water, soluble in ethanol, and very slightly soluble in acetone.
Identification (1) Dissolve 25.0 mg each of Buflomedil Hydrochloride and Buflomedil Hydrochloride RS in
ethanol to make exactly 50 mL. Dilute 2.0 mL of the solutions with ethanol to 20 mL. Determine the absorption
spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared absorption spectra of Buflomedil Hydrochloride and Buflomedil Hydrochloride
(3) Dissolve 40 mg each of Buflomedil Hydrochloride and Buflomedil Hydrochloride RS in 2 mL of methanol, and use these solutions the test solution and the
standard solution, respectively. Perform the test with
indicator for thin-layer chromatography, develop with a
mixture of toluene, isopropanol, and triethyamine (50 :
50 : 5) to a distance of about 15 cm, and air-dry the plate.
Examine in ultraviolet light at 254 nm, and compare the
principal spot from the test solution with that from the
standard solution. Their Rf values are the same.
(4) The solution of Buflomedil Hydrochloride in water (1 in 200) responds to the Qualitative Tests for chloride.
of Buflomedil Hydrochloride in 50 mL of water is between 5.0 and 6.5.
Purity (1) Clarity and color of solutionWhen 2.5 g
of Buflomedil Hydrochloride is dissolved in 50 mL water, the resultant solution is colorless and clear.
(2) Heavy metals Proceed with 2.0 g of Buflomedil Hydrochloride according to Method 2 and perform
the test. Prepare the control solution with 2.0 mL of
(3) Related substancesDissolve 0.10 g of Buflomedil Hydrochloride in the mobile phase to make exactly
10 mL, and use this solution as the test solution. Dilute
0.5 mL of the test solution to 100 mL with the mobile
phase. Dilute 5 mL of this solution to 10 mL with the
mobile phase, and use this solution as the standard solution (1). Separately, dissolve 2 mg of Buflomedil Hydrochloride Related Substance I RS [4-(pyrrolidin-1-yl)1-(4-hydroxy-2,6-dimethoxyphenyl)butan-1-one] in the
mobile phase, add 0.5 mL of the test solution and dilute

to 100 mL with the mobile phase, and use this solution as
the standard solution (2). Perform the test with 10 L
each of the test solution and the standard solutions as directed under the Liquid Chromatography according to
the following conditions. Determine the area of each
peak by the automatic integration method. The peak area
of any related substance from the test solution is not
more than the principal peak area from with the standard
solution (1) (0.25%); and the sum of the peak areas of all
related substances is not more than twice the principal
peak area from the standard solution (1) (0.5%). Disregard any peak areas that are not more than 0.2 times the
principal peak area from the standard solution (1)
(0.05%).
Column temperature: At a constant temperature of
about 40 C.
Mobile phase: A mixture of phosphate buffer solution
at pH 2.5 and acetonitrile (55:45).
Flow rate: 1 mL/min.
System suitability
operating conditions, the resolution between the peak of
buflomedil and the related substance I is not less than 5.0.
Time span of measurement: 2 times as long as the
retention time of buflomedil.
Phosphate buffer solutionDissolve 9.25 g of potassium dihydrogen phosphate in water to make 1000 mL
and adjust the solution pH to 2.5 with phosphoric acid.
hours).
Assay Dissolve 0.3 g of Buflomedil Hydrochloride,
accurately weighed, in 15 mLof glacial acetic acid, add
35 mL of acetic anhydride, and titrate with 0.1 mol/L
KP 9 135
Bumetanide
CO2H
O
H2N
NHCH2CH2CH2CH3
S
O
C17H20N2O5S: 364.42
Bumetanide, when dried, contains not less than 98.5%
and not more than 101.0% of bumetanide(C17H20N2O5S).
Description Bumetanide is a white crystal or crystalline powder.
Bumetanide is freely soluble in pyridine, soluble in methanol and in ethanol, slightly soluble in ether and practically insoluble in water.
Bumetanide dissolves in sodium hydroxide TS.
Bumetanide is gradually colored by light.
Identification (1) Dissolve 10 mg of Bumetanide in 1
mL of pyridine, add 2 drops of cupric sulfate TS, shake,
add 3 mL of water and 5 mL of chloroform, shake and allow to stand: a pale blue color develops in the chloroform layer.
(2) Dissolve 40 mg each of Bumetanide and Bumetanide RS in 100 mL of phosphate buffer solution, pH 7.0.
To 10 mL of these solutions, add water to make 100 mL
and determine their absorption spectra as directed under
(3) Determine the infrared spectra of Bumetanide and
Bumetanide RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Melting Point
Purity (1) Clarity and color of solution Dissolve 50

mg of Bumetanide in 2 mL of a solution of potassium
hydroxide (1 in 30) and 8 mL of water: the solution is
clear and has no more color than the following control
solution.
Control solutionsPipet 0.5 mL each of cobaltous
chloride stock CS, ferric chloride stock CS and cupric
sulfate stock CS, mix and add diluted hydrochloric acid
(1 in 40) to make exactly 100 mL.
(2) Chloride Mix well 0.5 g of Bumetanide with
0.7 g of potassium nitrate and 1.2 g of anhydrous sodium
carbonate, transfer, in small portions, to a red-hot plati-
num crucible and heat until the reaction is complete. After cooling, to the residue, add 14 mL of dilute sulfuric
acid and 6 mL of water, boil for 5 minutes, filter, wash
the residue, with 10 mL of water, combine the filtrate and
the washing and add 6 mL of dilute nitric acid and water
to make 50 mL. Perform the test using this solution as
0.021%).
(3) Heavy metalsProceed with 2.0 g of Bumetanide according to Method 2 and perform the test. Prepare
Bumetanide according to Method 3 and perform the test
exposure to daylight, using light-resistant vessels. Dissolve 0.10 g of Bumetanide in 10 mL of methanol and
use this solution as the test solution. Pipet 1 mL of the
test solution and add methanol to make exactly 100 mL.
Pipet 2 mL of this solution, add methanol to make exactly 10 mL and use this solution as the standard solution.
Perform the test with the test solution and standard solution as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator
mixture of chloroform, glacial acetic acid, cyclohexane
and methanol (32 : 4 : 4 : 1) to a distance of about 12 cm
hours).
Assay Weigh accurately about 0.5 g of Bumetanide,
previously dried, dissolve in 50 mL of ethanol and titrate
with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry), Perform a blank determination and make any necessary correction.
= 36.442 mg of C17H20N2O5S
tight containers.
Bunazosin Hydrochloride
O
CH3O
CH2CH2CH3
HCl
N
CH3O
NH2
C19H27N5O3.HCl: 409.91
Bunazosin Hydrochloride, when dried, contains not less
than 98.0% and not more than 101.0% of bunazosin hydrochloride (C19H27N5O3HCl).
Description Bunazosin Hydrochloride is a white crystalline powder.
Bunazosin Hydrochloride is very soluble in formic acid,
slightly soluble in methanol, very slightly soluble in dehydrated ethanol and practically insoluble in ether.
o
Identification (1) Dissolve 0.1 g of Bunazosin Hydrochloride in 10 mL of 0.2 mol/L hydrochloric acid TS
and boil for 3 minutes over a flame: butylic acid like
odor is perceptible.
(2) Determine the infrared spectra of Bunazosin Hydrochloride and Bunazosin Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
(3) A solution of Bunazosin Hydrochloride (1 in 100)
Purity (1) Heavy metalsProceed with 1.0 g of Bunazosin Hydrochloride according to Method 4 and perform
(2) Related substancesDissolve 50 mg of Bunazosin Hydrochloride in 50 mL of the mobile phase and use
this solution as the test solution. To exactly 1 mL of the
mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution and the
standard solution as directed under the Liquid Chromatography, according to the following conditions. Determine each peak area of both solutions by the automatic
integration method: the total area of the peaks other than
the peak of bunazosin from the test solution is not larger
than the peak area of bunazosin from the standard solution.
Column: A stainless steel column, about 4 mm in in-
side diameter and about 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
about 30 C.
Mobile phase: Dissolve 1.44 g of sodium lauryl sulfate in a suitable amount of water, add 10 mL of glacial
acetic acid, 500 mL of acetonitrile and water to make
1000 mL.
time of bunazosin is about 5 minutes.
System suitability
System performance: When the procedure is run with 20
L of the standard solution and a solution of Procaine
Hydrochloride in the mobile phase (1 in 20000)-(1:1)
under the above operating conditions, procaine and bunazosin are eluted in this order with the resolution between their peaks being not less than 3.0.
Detection sensitivity: Adjust the detection sensitivity so
that the peak height of bunazosin obtained from 20 L of
the standard solution is 20 to 60% of the full-scale.
Time span of measurement: About 6 times of the retention time of bunazosin.
hours).
Assay Weigh accurately 0.3 g of Bunazosin Hydrochloride, previously dried, dissolve in 6 mL of formic acid,
add exactly 15 mL of 0.1 mol/L perchloric acid and heat
for 20 minutes in a water-bath. After cooling, add 20 mL
of glacial acetic acid and titrate the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform

Bupranolol Hydrochloride
H 3C
OH
OCH 2CCH2NHNC(CH 3)3
HCl
H
Cl
C14H22ClNO2.HCl: 308.24
Bupranolol Hydrochloride, when dried, contains not less
than 98.0% and not more than 101.0% of bupranolol hydrochloride (C14H22ClNO2HCl).
KP 9 137
Description Bupranolol Hydrochloride is a white crystalline powder.

Bupranolol Hydrochloride is sparingly soluble in methanol, in ethanol or in glacial acetic acid, very slightly soluble in acetic anhydride and practically insoluble in ether.
pH Dissolve 1.0 g of Bupranolol Hydrochloride in
1000 mL water: the pH of this solution is between 5.2
and 6.2.
.
Identification (1) Take 10 mg of Bupranolol Hydrochloride in a test tube, mix with 25 mg of potassium iodide
and 25 mg of oxalic acid, cover the mouth of the test
tube with a filter paper, moistened with a solution of 2,6dibromoquinone chloride in ethanol (1 in 100) and heat
gently for several minutes. Expose the filter paper to
ammonia gas: the filter paper acquires a blue color.
of Bupranolol Hydrochloride and Bupranolol Hydrochloride RS in 0.1 mol/L hydrochloric acid TS (1 in 10000)
(3) Determine the infrared spectra of Bupranolol Hydrochloride and Bupranolol Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
(4) A solution of Bupranolol Hydrochloride (1 in
200) responds to the Qualitative Tests for chloride.
%
Absorbance E11cm
(275 nm): Between 57 and 60 (after
drying, 50 mg, 0.1 mol/L hydrochloric acid TS, 500 mL).

0.10 g of Bupranolol Hydrochloride in 15 mL of water:
the solution is clear and colorless.
(2) AcidDissolve 0.10 g of Bupranolol Hydrochloride in 15 mL of freshly boiled and cooled water and add
1 drop of methyl red TS: a light red color is observed. To
this solution, add 50 L of 0.01 mol/L sodium hydroxide
VS: the color changes to yellow.
(3) SulfatePerform the test with 0.10 g of Bupranolol Hydrochloride. Prepare the control solution with
0.168%).
(4) Heavy metalsProceed with 1.0 g of Bupranolol
(5) ArsenicPrepare the test solution with 1.0 g Bupranolol Hydrochloride according to Method 3 and perform the test (not more than 2 ppm).
(6) Related substancesDissolve 0.30 g of Bupranolol Hydrochloride in 10 mL of methanol and use this
solution as the test solution. Pipet 1 mL of the test solution, add methanol to make exactly 100 mL and use this
silica gel with a fluorescent indicator for thin-layer
chromatography. Develop the plate with a mixture of methanol, strong ammonia water and water (16 : 4 : 1) to a
hours).
Assay Weigh accurately 0.18 g of Bupranolol Hydrochloride, previously dried, dissolve in 60 mL of a
by warming, cool and titrate with 0.1 mol/L perchloric
acid VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and
= 30.824 mg of C14H22ClNO2.HCl
Buspirone Hydrochloride
N
HCl
N
O
C21H31N5O2HCl : 421.96
Buspirone Hydrochloride contains not less than 97.5%
and not more than 102.5% of buspirone hydrochloride
Description Buspirone Hydrochloride is a white, crystalline powder.
Buspirone Hydrochloride is very soluble in water, freely
soluble in methanol or in dichlormethane, sparingly soluble in ethanol or in acetonitrile, very slightly soluble in
ethyl acetate, and practically insoluble in hexane.

spectra of Buspirone Hydrochloride and Buspirone Hydrochloride RS as directed in the potassium bromide disk
same wavenumbers.
(2) When the procedure in the Assay is performed,
the relative retention time of the principal peak from the
test solution corresponds to that from the standard solution.
Purity (1) Heavy metalsProceed with 1.0 g of Buspirone Hydrochloride, according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
standard lead solution (20 ppm).
(2) ChlorideDissolve about 0.4 g, accurately
weighed, in 20 mL of water. Add 3 mL of nitric acid and
20 mL of 0.1 mol/L silver nitrate VS, gently boil the
mixture for about 5 minutes, and filter. Rinse the flask
with about 80 mL of water divided into small portions,
and filter each portion. To all combined filtrates, add 2
mL of 8% ferric ammonium sulfate, and stir rapidly
while titrating from a buret with 0.1 mol/L ammonium
thiocyanate VS to a faint red-brown endpoint (8.0
8.8%).
Column: A stainless steel column 3.0 mm inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase: A mixture of phosphate buffer solution
and acetonitrile (60:40).
System suitability
with 25 L of the standard solution according to the
above operating conditions, the resolution between the
peaks of buspirone hydrochloride and the internal standard is not less than 4.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of buspirone hydrochloride to that of the internal standard is not more than 2.0.
Buffer solutionDissolve 1.36 g of monobasic potassium phosphate in water to make 1000 mL, and adjust
the solution with 10% sodium hydroxide to a pH of 7.5.

= 3.545 mg of chloride
Busulfan

direct titration).
O
H3C
S
O
Assay Dissolve about 50 mg each of Buspirone Hydrochloride and Buspirone Hydrochloride RS, accurately
weighed, in 1 mol/L to make 25 mL, dilute with water to
make 100 mL. To 10 mL of these solutions, add 10 mL
of the internal standard, and dilute with water to make 50
mL. Use these solutions as the test solution and the standard solution, respectively. Perform the test with 25 L
the following conditions, and calculate the ratios, QT
and QS , of the peak area of Buspirone Hydrochloride.
Amount (mg) of buspirone hydrochloride
(C21H31N5O2HCl)
= amount (mg) of Buspirone Hydrochloride RS
QT
QS
Internal standard solutionDissolve 0.25 g of

propyl parahydroxybenzoate in methanol to make 100
mL. Dilute 25 mL of this solution with water to 500 mL.
O
OCH2CH2CH2CH2O
CH3
C6H14O6S2: 246.30
Busulfan contains not less than 98.5% and not more than
101.0% of busulfan (C6H14O6S2), calculated on the dried
basis.
Description Busulfan is a white, crystalline powder
and is odorless.
Busulfan is slightly soluble in ether, very slightly soluble
in ethanol and practically insoluble in water.
Identification (1) To 0.1 g of Busulfan, add 10 mL of
water and 5 mL of sodium hydroxide TS, dissolve by
heating and use this solution as the test solution. (i) To 7
mL of the test solution, add 1 drop of potassium permanganate TS: the red-purple color of potassium permanganate TS changes from blue-purple trough blue to green.
(ii) Acidify 7 mL of the test solution with dilute sulfuric
acid and add 1 drop of potassium permanganate TS: the
color of potassium permanganate TS remains.
(2) Determine the infrared spectra of Busulfan and
Busulfan RS as directed in the potassium bromide disk
same wavenumbers.
KP 9 139
Melting Point
Purity (1) SulfateTo 1.0 g of Busulfan, add 40 mL

of water and dissolve by heating. Cool in ice for 15 minutes and filter. Wash the residue with 5 mL of water,
combine the washings with the filtrate and add 1 mL of
dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.005 mol/L
(2) Heavy metalsProceed with 1.0 g of Busulfan
soluble matter to settle and finally decanting the supernatant liquid through a sintered-glass filter (G4). Evaporate
the collection of extracts to about 10 mL, add phenolphthalein TS and neutralize with 0.1 mol/L sodium hydroxide. Evaporate to dryness, add about 30 mL of water and
proceed as directed under the Assay of Busulfan with reflux condenser (indicator : 3 drops of phenolphthalein TS).
= 12.315 mg of C6H14O6S2
Caffeine

P2O5, 60 C, 4 hours).
O
H3C

Assay Weigh accurately about 0.2 g of Busulfan, add
40 mL of water and boil gently under a reflux condenser
for 30 minutes. Cool and titrate with 0.1 mol/L sodium
hydroxide VS (indicator: 3 drops of phenolphthalein TS).
= 12.315 mg of C6H14O6S2
Busulfan Tablets
Busulfan Tablets contains not less than 93.0% and not
more than 107.0% of the labeled amount of busulfan
(C6H14O6S2: 246.30).
Method of Preparation Prepare as directed under Tablets, with Busulfan.
Identification Powder Busulfan Tablets and extract the
powder several times with acetone. Collect these extracts
and evaporate to dryness in a water-bath, with the aid of
a current of air. The residue responds to Identification
test (1) and (2) of Busulfan, and melts at about 115 C.
Assay Weigh and finely powder not less than 40 tablets
(caution: guard against accidental inhalation of fine
powder). Weigh accurately a portion of powder, equivalent to about 80 mg of busulfan (C6H14O6S2) and transfer
to a beaker. Extract with four 20 mL volumes of acetone,
each time stirring the mixture well, then allowing the in-

CH3
N
N
N
O
N
CH3
Anhydrous Caffeine
C8H10N4O2: 194.19
Caffeine, when dried, contains not less than 98.5% and

not more than 101.0% of caffeine (C8H10N4O2).
Description Caffeine is a white crystal or powder, is
odorless and has a bitter taste.
Caffeine is freely soluble in chloroform, sparingly soluble in water, in acetic anhydride or in glacial acetic acid and slightly soluble in ethanol or in ether.
pH A solution of Caffeine (1 in 100) is between
5.5 and 6.5
Identification (1) To 2 mL of a solution of Caffeine (1
in 500), add tannic acid TS drop-wise: a white precipitate,
which dissolves upon the drop-wise addition of tannic
acid TS, is produced.
(2) To 10 mg of Caffeine, add 10 drops of hydrogen
peroxide TS and 1 drop of hydrochloric acid and evaporate on a water-bath to dryness: the residue acquires a
yellow-red color. Invert the residue over a vessel containing 2 to 3 drops of ammonia TS: the color turns a redpurple and disappears upon the addition of 2 to 3 drops
of sodium hydroxide TS.
(3) Dissolve 10 mg of Caffeine in water to make 50
mL. To 5 mL of this solution, add 3 mL of diluted acetic
acid (3 in 100) and 5 mL of pyridine (1 in 10), mix, add 2
mL of diluted sodium hypochlorite TS (1 in 5) and allow
to stand for 1 minute. Add 2 mL of sodium thiosulfate TS
and 5 mL of sodium hydroxide TS to the solution: a yellow color develops.
Melting Point
Purity Test (1) ChlorideDissolve 2.0 g of Caffeine

in 80 mL of hot water, cool rapidly to 20 C, add water to
make 100 mL and use this solution as the test stock solution. To 40 mL of the test stock solution, add 6 mL of dilute nitric acid and water to make 50 mL. Perform the
control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.011%).
(2) SulfateTo 40 mL of the test stock solution obtained in (1), add 1 mL of dilute hydrochloric acid and
0.024%).
(3) Heavy metalsProceed with 2.0 g of Caffeine
(4) Related substancesDissolve 0.10 g of Caffeine
in 10 mL of chloroform and use this solution as the test
solution. Pipet 1 mL of the test solution and add chloroform to make exactly 100 mL. Pipet 1 mL of this solution, add chloroform to make exactly 10 mL and use this
silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and ethanol (9 : 1) to a distance of about 10 cm and
air-dry the plate. Examine under ultraviolet light (main
wavelength: 254 nm): the spots other than the principal
spot from the standard solution.
(5) Readily carbonizable SubstancesPerform the
test using 0.5 g of Caffeine: the solution has no more
color than Color Matching Fluid D.
hours).
Assay Weigh accurately 0.4 g of Caffeine, previously
dried, dissolve in 70 mL of a mixture of acetic anhydride
and glacial acetic acid (6 : 1) and titrate with 0.1 mol/L
perchloric acid VS until the solution changes from purple
through green to yellow (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination
= 19.419 mg of C8Hl0N4O2
Caffeine Hydrate
O
H 3C
CH3
N
N
H2O
N
O
N
CH3
C8Hl0N4O2H2O: 212.21
Caffeine Hydrate, previously dried, contains not less than
98.5% and not more than 101.0% of caffeine (C8Hl0N4O2:
194.19).
Description Caffeine Hydrate is a white, soft crystal or
powder, is odorless and has a slightly bitter taste.
Caffeine Hydrate is freely soluble in chloroform, sparingly soluble in water, in glacial acetic acid or in acetic
anhydride, slightly soluble in ethanol and very slightly
soluble in ether.
pH A solution of Caffeine Hydrate (1 in 100) is
Caffeine Hydrate effloresces in dry air.
Identification (1) To 2 mL of a solution of Caffeine
Hydrate (1 in 500), add tannic acid TS drop-wise: a
white precipitate, which dissolves upon the drop-wise
addition of tannic acid TS, is produced.
(2) To 10 mg of Caffeine Hydrate, add 10 drops of
hydrogen peroxide TS and 1 drop of hydrochloric acid
and evaporate to dryness on a water-bath: the residue acquires a yellow-red color. Invert the residue over a vessel
containing 2 to 3 drops of ammonia TS: the color turns
red-purple and disappears upon the addition of 2 to 3
drops of sodium hydroxide TS.
(3) Dissolve 10 mg of Caffeine Hydrate in water to
make 50 mL. To 5 mL of this solution, add 3 mL of diluted acetic acid (3 in 100) and 5 mL of a solution of pyridine (1 in 10), mix, add 2 mL of diluted sodium hypochlorite TS (1 in 5) and allow to stand for 1 minute.
Add 2 mL of sodium thiosulfate TS and 5 mL of sodium
hydroxide TS to the solution: a yellow color develops.
Melting Point
ing).
Between 235 C and 238 C (after dry-
Purity (1) ChlorideDissolve 2.0 g of Caffeine Hydrate in 80 mL of hot water, cool rapidly to 20 C, add
water to make 100 mL and use this solution as the test
stock solution. To 40 mL of the test stock solution, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.011%).
(2) SulfateTo 40 mL of the test stock solution obtained in (1), add 1 mL of dilute hydrochloric acid and
KP 9 141
0.024%).
(3) Heavy metalsProceed with 2.0 g of Caffeine
(4) Related substancesDissolve 0.10 g of Caffeine
Hydrate in 10 mL of chloroform and use this solution as
the test solution. Pipet 1 mL of the test solution and add
chloroform to make exactly 100 mL. Pipet 1 mL of this
solution, add chloroform to make exactly 10 mL and use
this solution as the standard solution. Perform the test as
a plate of silica gel with fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
of chloroform and ethanol (9 : 1) to a distance of about
(5) Readily carbonizable substancePerform the
test using 0.5 g of Caffeine Hydrate: the solution has no
more color than Color Matching Fluid D.
Loss on Drying Between 0.5 and 8.5% (1 g, 80 C, 4
hours).
Assay Weigh accurately about 0.4 g of Caffeine Hydrate, previously dried, dissolve in 70 mL of a mixture of
acetic anhydride and glacial acetic acid (6 : 1) and titrate
with 0.1 mol/L perchloric acid VS until the solution
changes from purple through green to yellow (indicator:
3 drops of methylrosaniline chloride TS). Perform a
= 19.419 mg of C8Hl0N4O2
Caffeine and Sodium Benzoate

Caffeine and Sodium Benzoate, when dried, contains not
less than 48.0% and not more than 50.0% of caffeine
more than 52.0% of sodium benzoate (C7H5NaO2:
144.10).
Description Caffeine and Sodium Benzoate is a white
Caffeine and Sodium Benzoate is freely soluble in water,
soluble in glacial acetic acid or in acetic anhydride, spa-
ringly soluble in ethanol and practically insoluble in ether.

Identification (1) Dissolve 1 g of Caffeine and Sodium
Benzoate in 10 mL of water in a separator, add 1 drop of
phenolphthalein TS and add carefully 0.01 mol/L sodium
hydroxide VS dropwise until a pale red color develops.
Extract with three 20 mL volume of chloroform by thorough shaking and separate the chloroform layer from
the water layer [use the water layer for test (2).]. Filter
the combined chloroform extracts, evaporate the filtrate
to dryness in a water-bath and proceed the following
tests with the residue. (i) To 2 mL of a solution of the residue (1 in 500), add tannic acid TS drop-wise: a white
precipitate, which dissolves upon the drop-wise addition
of tannic acid TS, is produced. (ii) To 10 mg of the residue, add 10 drops of hydrogen peroxide TS and 1 drop of
hydrochloric acid, evaporate to dryness on a water-bath:
the residue acquires a yellow-red color. Invert the residue
over a vessel containing 2 to 3 drops of ammonia TS: the
color turns red-purple and disappears upon the addition
of 2 to 3 drops of sodium hydroxide TS. (iii) Dissolve 10
mg of the residue in water to make 50 mL. To 5 mL of
this solution, add 3 mL of diluted acetic acid (3 in 100)
and 5 mL of a solution of pyridine (1 in 10), mix, add 2
mL of diluted sodium hypochlorite TS (1 in 5) and allow
to stand for 1 minute. Add 2 mL of sodium thiosulfate TS
and 5 mL of sodium hydroxide TS to the solution: a yellow color develops.
(2) To 5 mL of the water layer obtained in (1), add 5
mL of water: the solution responds to the Qualitative
Tests (2) for benzoate.
(3) Heat Caffeine and Sodium Benzoate: white fumes
are evolved. Ignite furthermore and to the residue, add
hydrochloric acid: bubbles are produced and the solution
responds to the Qualitative Tests (1) for sodium salt.
1.0 g of Caffeine and Sodium Benzoate in 5 mL of water:
(2) AlkaliDissolve 1.0 g of Caffeine and Sodium
Benzoate in 20 mL of water and add 1 or 2 drops of phenolphthalein TS: no red color develops.
(3) ChlorideDissolve 0.5 g of Caffeine and Sodium Benzoate in 10 mL of water and add 30 mL of
ethanol, 6 mL of dilute nitric acid and water to make 50
mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.70 mL of 0.01
mol/L hydrochloric acid VS, 30 mL of ethanol and water
to make 50 mL (not more than 0.050%).
(4) Chlorinated compoundsDissolve 1.0 g of
Caffeine and Sodium Benzoate in 40 mL of water, add
10 mL of dilute sulfuric acid and extract with two 2 mL
volumes of ether. Allow the combined ether extracts to
evaporate at room temperature to dryness. Place this residue and 0.7 g of calcium carbonate in a crucible, mix
with a small amount of water and dry. Ignite at about 600
C, dissolve the residue in 20 mL of dilute nitric acid and
filter. Wash the residue with 15 mL of water, combine the

filtrate and the washings and add water to make 50 mL.
To this solution, add 0.5 mL of silver nitrate TS: the solution shows no more turbidity than the following control
solution to which 0.5 mL of silver nitrate TS has been
added.
Control solutionDissolve 0.7 g of calcium carbonate in 20 mL of dilute nitric acid and filter. Wash the residue with 15 mL of water, combine the filtrate and the
washings and add 1.2 mL of 0.01 mol/L hydrochloric acid VS and water to make 50 mL.
Each mL of 0.1 mol/L perchloric acid-dioxane VS

= 14.411 mg of C7H5NaO2
(2) CaffeineContinue the titration in (1) with 0.1
mol/L perchloric acid-dioxane VS from the first equivalence point to the second equivalence point (potentiometric titration, Endpoint Detection Method in Titrimetry).
= 19.419 mg of C8H10N4O2
(5) Heavy metalsDissolve 2.0 g of Caffeine and

Sodium Benzoate in 47 mL of water, add slowly, with
vigorous stirring, 3 mL of dilute hydrochloric acid and
filter. Discard the first 5 mL of the filtrate, neutralize the
subsequent 25 mL of the filtrate with ammonia TS and
add 2 mL of dilute acetic acid and water to make 50 mL.
solution by adding 2 mL of dilute acetic acid and water
to make 50 mL (not more than 20 ppm).
Caffeine and Sodium Benzoate according to Method 1
and perform the test (not more than 2 ppm).
(7) Phthalic acidTo 0.10 g of Caffeine and Sodium
Benzoate, add 1 mL of water and 1 mL of resorcinsulfuric acid TS and heat the mixture in an oil-bath
heated at a temperature between 120 C and 125 C to
evaporate the water, then heat the residue for further 90
minutes, cool and dissolve in 5 mL of water. To 1 mL of
the solution add 10 mL of a solution of sodium hydroxide (43 in 500), shake, then examine under light at a wavelength between 470 nm and 490 nm: the green fluorescence of the solution is not more intense than that of the
following control solution.
Control solutionDissolve 61 mg of potassium

biphthalate in water to make exactly 1000 mL. Pipet exactly 1 mL of the solution, add 1 mL of resorcin-sulfuric
acid TS and proceed as directed above.
Purity (1) Acid-insoluble substancesDissolve 2.0 g

of Calamine in 50 mL of 3 mol/L hydrochloric acid. Filter of an insoluble residue remains. Wash with water, dry
at 105 C for 1 hour, cool and weigh: the weight of the
residue does not exceed 40 mg (not more than 2.0%).
(2) Alkaline substancesAdd 1.0 g of Calamine to
20 mL of water in a water-bath for 15 minutes. Filter and
add 2 drops of phenolphthalein TS and 0.20 mL of 0.05
mol/L sulfuric acid: the color of the solution is colorless.
(3) LeadAdd 15 mL of water to 1 g of Calamine,
stir, then add 3 mL of glacial acetic acid. Warm on a
steam-bath until dissolved. Filter the mixture and add 5
drops of potassium chromate TS: no turbidity is produced.
(4) ArsenicDissolve 0.25 g of Calamine in 35 mL
of water and use this solution as the test solution and perform the test (not more than 8 ppm).
(5) CalciumDissolve 1 g of Calamine in 25 mL of
3 mol/L hydrochloric acid for 30 minutes and add 6
mol/L ammonium hydroxide to the filtrate until the precipitate first formed is dissolved, then add 5 mL more of
(8) Readily carbonizable substances Proceed with

0.5 g of Caffeine and Sodium Benzoate and perform the
test: the solution has no more color than Color Matching
Fluid A.
hours).
Assay (1) Sodium benzoateWeigh accurately 0.2 g
of Caffeine and Sodium Benzoate, previously dried, dissolve by warming in 50 mL of a mixture of acetic anhydride and glacial acetic acid for nonaqueous titration (6 :
1), cool and titrate with 0.1 mol/L perchloric aciddioxane VS to the first equivalence point (potentiometric
Calamine
Calamine is zinc oxide with a small proportion of ferric
oxide. Calamine contains, after ignition, not less than
98.0 and not more than 100.5% of zinc oxide (ZnO:
81.37).
Description Calamine is a pale pinkish fine powder, is
Calamine is insoluble in water.
Calamine dissolves in hydrochloric acid.
Identification (1) Dissolve 1 g of Calamine in 10 mL
of 3 mol/L hydrochloric acid and filter: the filtrate responds to the Qualitative Tests for zinc.
(2) Treat 1 g of Calamine with 10 mL of 3 mol/L hydrochloric acid, heat to boiling and filter: the filtrate produces reddish color upon the addition of ammonium thiocyanate TS.
KP 9 143
6 mol/L ammonium hydroxide. To 10 mL of this solution,
add 2 mL of ammonium oxalate TS: not more than a
slight turbidity is produced.
(6) Calcium or magnesiumTo another 10 mL portion of the solution prepared for the test for Calcium, add
2 mL of dibasic sodium phosphate TS: not more than a
slight turbidity is produced.
Loss on Ignition Not more than 2.0% (2 g).
Assay Dissolve about 1.5 g of freshly ignited Calamine,
accurately weighed, with 50 mL of 0.5 mol/L sulfuric acid VS. Filter the mixture and wash the residue on the filter with hot water until last washing is neutral. To the
combined filtrate and washings, add 2.5 g of the ammonium chloride, cool and titrate with 1 mol/L sodium hydroxide VS (indicator: 3 drops of methyl orange TS).
correction.
Each mL of 0.5 mol/L sulfuric acid = 40.69 mg of ZnO
Calcitriol
H
H3C
CH3
CH3
H
HO
CH3
Purity Related substancesPerform the test as directed under the Liquid Chromatography according to
the conditions in Assay. Determine the peak area of each
solution according to the automatic integration. Calculate
the peak areas of related substances, that are eluted within twice the retention time of Calcitriol obtained from the
test solution. Peak area of any individual related substance is not more than 5.0% of principal peak area and
the sum of the related substances is not more than 1.0%.
Disregard any peak with an area less than 0.1 times that
of the peak in the chromatogram obtained from standard
solution (2).
Assay Carry out the assay as rapidly as possible, avoiding exposure to actinic light and air. Weigh accurately 1
mg of Calcitriol, and dissolve in the mobile phase to
make exactly 10 mL, use this solution as the test solution.
Weigh accurately 1 mg of Calcitriol RS, and dissolve in
the mobile phase to make exactly 10 mL, and use this solution as the standard solution (1). Add the mobile phase
to 1.0 mL of this solution to make exactly 100 mL, use
this solution as the standard solution (2). Keep 2 mL of
standard solution (1) at 80 for 30 minutes, use this solution as the standard solution (3). Perform the test with
50 L each of test solution and standard solution (1) as
the following conditions, and calculate the peak areas of
Calcitriol of each solution, AT and AS , respectively.
Amount (mg) of calcitriol (C27H44O3) = 10 C
CH2
HO
metry: both spectra exhibit similar intensities of absorption at the same wave numbers.
(2) Retention time of the main peak obtained from
test solution and standard solution in the Assay is the
same.
AT
AS
C : Concentration (mg/mL) of Calcitriol obtained

from standard solution (1).
OH
H
C27H44O3 : 416.64
Calcitriol contains not less than 97.0% and not more than
103.0% of calcitriol (C27H44O3).
Description Calcitriol is a white crystals.
Calcitriol is freely soluble in ethanol, soluble in fatty oils,
Calcitriol is sensitive to air, heat and light.
A reversible isomerisation to pre-calcitriol takes place in
solution, depending on temperature and time.
Calcitriol and Calcitriol RS as directed in the potassium
bromide disk method under the Infrared Spectrophoto-
Detector: Ultraviolet-visible absorption Photometer
(wavelength: 230 nm).
octadecylsilanized silica gel for the liquid chromatography.
Column temperature: A constant teperature of about
40 C.
Mobile phase: A mixture of acetonitrile and trishydroxymethylaminomethane bufffer solution (550 : 450).
System suitability
operating conditions: the relative retention time of precalcitriol peak to calcitriol peak is about 0.9, the resolu-

tion between the peaks due to Calcitriol and pre-calcitriol
is not less than 3.5. Perform the test with 50 L of the
standard solution (1) according to the above operating
conditions, the number of theoretical plates is not than
10000.
above operating conditions: the relative standard deviation of peak area of calcitriol is not more than 1%.
Trishydroxymethylaminomethane buffer solution
Dissolve 1.0 g of trishydroxymethylaminomethane in
1000 mL of water. Adjust the pH between 7.0 and 7.5.
Packaging and Storage Preserve in a light-resistant,
tight containers, store under nitrogen at between 2 and 8
C. The contents of an opened container are to be used
immediately.
Calcium Chloride Hydrate

CaCl22H2O: 147.02
Calcium Chloride Hydrate contains not less than 96.7%
and not more than 103.3% of calcium chloride hydrate
(CaCl22H2O).
Description Calcium Chloride Hydrate is a white granule or mass and is odorless.
Calcium Chloride Hydrate is very soluble in water, soluble in ethanol, and practically insoluble in ether.
Calcium Chloride Hydrate is deliquescent.
Identification A solution of Calcium Chloride Hydrate
(1 in 10) responds to the Qualitative Test for calcium salt
and for chloride.
pH Dissolve 1.0 g of Calcium Chloride Hydrate in 20
mL of freshly boiled and cooled water: the pH of this solution is between 4.5 and 9.2.
Purity (1) Clarity and color of solutionA solution of
1.0 g of Calcium Chloride Hydrate in 20 mL of water is
clear and colorless.
(2) SulfateTake 1.0 g of Calcium Chloride Hydrate
0.024%).
(3) HypochloriteDissolve 0.5 g of Calcium Chloride Hydrate in 5 mL of water, add 2 to 3 drops of dilute
hydrochloric acid and 2 to 3 drops of zinc iodide-starch
TS: no blue color is observed immediately.
(4) Heavy metalsProceed with 2.0 g of Calcium
Chloride Hydrate according to Method 1 and perform the
(5) Iron, aluminum or phosphateDissolve, in a

Nessler tube, 1.0 g of Calcium Chloride Hydrate in 20
mL of water and 1 drop of dilute hydrochloric acid, boil,
then cool, add 3 drops of ammonia TS and heat the solution to boil: no turbidity or precipitate is produced.
(6) BariumDissolve 0.5 g of Calcium Chloride
Hydrate in 5 mL of water, add 2 drops of dilute hydrochloric acid and 2 mL of potassium sulfate TS and allow to
stand for 10 minutes: no turbidity is produced.
Calcium Chloride Hydrate according to Method 1 and
Assay Weigh accurately about 0.4 g of Calcium Chloride Hydrate and dissolve in water to make exactly 200
mL. Measure exactly 20 mL of this solution, add 40 mL
of water, 2 mL of 8 mol/L potassium hydroxide TS and
0.1 g of NN indicator and titrate with 0.02 mol/L of disodium ethylenediaminetetraacetate VS until the color of
the solution changes from red-purple to blue.
Each mL of 0.02 mol/L disodium ethylenediaminetetraacetate VS = 2.9402 mg of CaCl22H2O
Calcium Chloride Injection

Calcium Chloride Injection is an aqueous solution for injection. Calcium Chloride Injection contains not less than
of calcium chloride (CaCl2: 110.98).
The concentration of Calcium Chloride Injection is expressed as the quantity of calcium chloride (CaCl2:
110.98).
Do not perform the Pyrogen Test with Calcium Chloride
Injection.
Method of Preparation Prepare as directed under Injections, with Calcium Chloride Hydrate.
Description Calcium Chloride Injection is a clear colorless liquid.
Identification Calcium Chloride Injection responds to
the Qualitative Test for calcium salt and for chloride.
It
KP 9 145

Assay Measure exactly a volume of Calcium Chloride
Injection, equivalent to about 0.4 g of calcium chloride
(CaCl2) and proceed as directed in the Assay under Calcium Chloride Hydrate.
Each mL of 0.02 mol/L disodium ethylenediaminetetraacetate VS = 2.2197 mg of CaCl2
Calcium Folinate
H
N
H2N
H
N
H
CH2NH
CHO
Calcium Leucovorin
CONH
Assay Weigh accurately about 20 mg of Calcium Folinate, dissolve in the mobile phase to make exactly 100
weigh accurately about 17.5 mg of Calcium Folinate RS,
calculated on the anhydrous basis, dissolve in the mobile
under the Liquid Chromatography according to the following conditions and determine the peak areas, AT and
AS, of folinate for the test solution and the standard solution, respectively.
Ca2+
N
N
Water Weigh accurately about 0.2 g of Calcium Folinate in a dried titration flask and dissolve in 25 mL of
glacial acetic acid. Add 10.0 mL of standard watermethanol solution, titrate with Karl Fischer TS to the end
point and perform the test: it is not more than 17.0%.
correction.
CH2CH2CO2-
C
-
CO2
C20H21CaN7O7: 511.50
Calcium Folinate contains not less than 95.0% and not

more than 102.0% of calcium folinate (C20H21CaN7O7),
Description Calcium Folinate is a pale yellow to yellow powder, is odorless and tasteless.
Calcium Folinate is very soluble in water, freely soluble
in glacial acetic acid and practically insoluble in ethanol
or in ether.
Calcium Folinate is gradually affected by light.
solutions (1 in 100000) of Calcium Folinate and Calcium
Folinate RS as directed under the Ultraviolet-visible
(2) Determine the infrared spectra of Calcium Folinate and Calcium Folinate RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Calcium Folinate (1 in 100) responds to the Qualitative Tests (2), (3) and (4) for calcium salt.
1.0 g of Calcium Folinate in 10 mL of water: the solution
is clear and yellow.
Folinate according to Method 2 and perform the test.
Amount (mg) of calcium folinate (C20H21CaN7O7)

= amount (mg) of Calcium Folinate RS,
AT
calculated on the anhydrous basis A
S
Mobile phase: To 860 mL of water, add 100 mL of
acetonitrile and 15 mL of tetrabutylammonium hydroxide-methanol TS, adjust the pH to 7.5 with 2 mol/L monobasic sodium phosphate TS and add water to make
1000 mL.
time of folinate is about 10 minutes.
System suitability
System performance: Dissolve 17.5 mg of folic acid in 100 mL of the mobile phase and to 5 mL of this solution add 20 mL of the standard solution. When the procedure is run with 20 L of this solution under the above
operating conditions, folinate and folic acid are eluted in
this order with the resolution of their peaks being not less
than 3.6.
above operating conditions, the relative standard deviation of each peak area of folinate is not more than 2.0%.
tight containers.
Calcium Gluconate Hydrate
HOH2C
OH
OH
OH
OH
Ca2+
CO2
H2O
Calcium Gluconate
C12H22CaO14H2O: 448.39
Calcium Gluconate Hydrate, when dried, contains not

less than 99.0% and not more than 104.0% of calcium
gluconate hydrate (C12H22CaO14H2O).
Description Calcium Gluconate Hydrate is a white,
crystalline powder or granule.
Calcium Gluconate Hydrate is freely soluble in hot water,
soluble in water and practically insoluble in dehydrated
ethanol.
Identification (1) To 10 mg each of Calcium Gluconate Hydrate and Calcium Gluconate Hydrate RS, add 1
mL of water each, dissolve by warming, and use these
solutions as the test solution and standard solution, respectively. Perform the test with these solutions as directed under the Thin-layer Chromatography. Spot 5 L
each of the test solution and standard solution on a plate
plate with a mixture of ethanol, water, ammonia solution
and ethyl acetate (5:3:1:1) to a distance of about 10 cm,
air-dry the plate, and heat the plate at 110 for 20 minutes. After cooling, spray evenly a mixture containing
molybdate sulfate TS and cerium sulfate TS on the plate,
air-dry, and heat at 110 C for 10 minutes: the spots with
the test solution and the standard solution are the same in
the Rf value and color tone.
(2) A solution of Calcium Gluconate Hydrate (1 in
40) responds to the Qualitative Tests for calcium salt.
drate and perform the test. Prepare the control solution

with 1.0 mL of 0.005 mol/L sulfuric acid VS (not more
than 0.048%).
(4) Heavy metalsDissolve 1.0 g of Calcium Gluconate Hydrate in 30 mL of water and 2 mL of dilute
acetic acid by warming, cool and add water to make 50
mL. Perform the test with this solution as the test solution. Prepare the control solution with 2.0 mL of standard
lead solution, 2 mL of dilute acetic acid and water to
(5) ArsenicDissolve 0.6 g of Calcium Gluconate
Hydrate in 5 mL of water by warming, add 5 mL of dilute sulfuric acid and 1 mL of bromine TS and concentrate in a water-bath to 5 mL use this solution as the test
solution and perform the test (not more than 3.3 ppm).
(6) Sucrose and reducing sugarsTo 0.5 g of Calcium Gluconate Hydrate, add 10 mL of water and 2 mL
of dilute hydrochloric acid and boil the solution for 2
minutes. After cooling, add 5 mL of sodium carbonate
TS, allow to stand for 5 minutes, add water to make 20
mL and filter. To 5 mL of the filtrate, add 2 mL of Fehlings TS and boil for 1 minute: no orange-yellow to red
precipitate is produced immediately.
hours).
Assay Weigh accurately 0.4 g of Calcium Gluconate
Hydrate, previously dried, dissolve in 100 mL of water,
add 2 mL of 8 mol/L potassium hydroxide TS and 0.1 g
of NN indicator and titrate immediately with 0.05 mol/L
disodium ethylenediaminetetraacetate VS until the color
of the solution changes from red-purple to blue.
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 22.420 mg of C12H22CaO14H2O
Calcium Gluconate Injection
20
Specific Optical Rotation nD : +6 ~ +11 (after drying, 0.5g, water, 25 mL, 100 mm).
pH Dissolve 1.0 g of Calcium Gluconate Hydrate in 20
mL of water by warming: the pH of the solution is between 6.0 and 8.0.
Purity (1) Clarity of solutionDissolve 1.0 g of Calcium Gluconate Hydrate in 50 mL of water by warming:
the solution is clear.
(2) ChlorideTake 0.40 g of Calcium Gluconate
Hydrate and perform the test. Prepare the control solution with 0.80 mL of 0.010 mol/L hydrochloric acid VS
(3) SulfateTake 1.0 g of Calcium Gluconate Hy-
Calcium Gluconate Injection is an aqueous solution for

injection. Calcium Gluconate Injection contains not less
amount of total calcium (Ca: 40.08).
An adequate amount of calcium saccharate or other suitable calcium salts may be added as stabilizers.
Method of Preparation Prepare as directed under Injections, with Calcium Gluconate Hydrate. Indicate the
amount of total calcium if any stabilizers are added.
Description Calcium Gluconate Injection is a clear and
colorless liquid.
Identification (1) Pipet about 5.0 mL of Calcium Glu-
KP 9 147
conate Injection. Add 0.7 mL of glacial acetic acid and 1
mL of freshly distilled phenylhydrazine and heat the solution in a water-bath for 30 minutes. Cool and perform
the test according to Identification (1) under Calcium
Gluconate Hydrate.
(2) An aqueous solution of Calcium Gluconate Injection (1 in 5) responds to the Qualitative Tests for calcium.
Bacterial Endotoxins Less than 0.17 EU per g of Calcium Gluconate Hydrate.
It

Assay Measure accurately a volume of Calcium Gluconate Injection equivalent to about 0.4 g of Calcium
Gluconate, add 100 mL of water, 2 mL of 8 mol/L potassium hydroxide TS and 0.1 mg of NN indicator. Immediately after the addition, titrate with 0.05 mol/L disodium ethylenediamine-tetraacetate VS until the solution
becomes blue.
Each mL of 0.05 mol/L disodium ethlendiaminetetraacetate VS = 2.0040 mg of Ca
nary temperature and yields the anhydride at 120 C.

Identification A solution of Calcium Lactate Hydrate
(1 in 20) responds to the Qualitative Tests for calcium
salt and for lactate.
Purity (1) Clarity of solutionDissolve 1.0 g of Calcium Lactate Hydrate in 20 mL of water by warming: the
solution is clear.
(2) Acid or alkaliTo the solution obtained in (1),
add 2 drops of phenolphthalein TS: no red color is produced. Then add 0.50 mL of 0.1 mol/L sodium hydroxide
VS: a red color develops.
(3) Heavy metalsDissolve 1.0 g of Calcium Lactate Hydrate in 30 mL of water and 5 mL of dilute acetic
acid by warming, cool, add water to make 50 mL and
perform the test using this solution as the test solution.
solution and 2 mL of dilute acetic acid and dilute with
water to make 50 mL (not more than 20 ppm).
(4) Magnesium or alkali metalsDissolve 1.0 g of
Calcium Lactate Hydrate in 40 mL of water, add 0.5 g of
ammonium chloride, boil, then add 20 mL of ammonium
oxalate TS. Heat the mixture in a water-bath for 1 hour,
cool, dilute with water to make 100 mL and filter, To 50
mL of the filtrate, add 0.5 mL of sulfuric acid, evaporate
to dryness and ignite between 450 C and 550 C to a
constant mass: the weight of the residue is not more than
5 mg.
(5) ArsenicDissolve 0.5 g of Calcium Lactate Hydrate in 2 mL of water and 3 mL of hydrochloric acid,
use this solution as the test solution. and perform the test
(6) Volatile fatty acidWarm 1.0 g of Calcium Lactate Hydrate with 2 mL of sulfuric acid: an odor of acetic
acid or butyric acid is not perceptible.
Loss on Drying Between 25.0 and 30.0% (1 g, 80 C,
1 hour at first, then 120 C, 4 hours).
Calcium Lactate Hydrate

OH
-
CH3CCO2
H
2+
Ca
5H2O
C6H10CaO6.5H2O: 308.29
Calcium Lactate Hydrate, when dried, contains not less
than 97.0% and not more than 101.0% of calcium lactate
(C6H10CaO6: 218.22).
Description Calcium Lactate Hydrate is a white powder or granule, is odorless and has a slightly acid taste.
1 g Of Calcium Lactate Hydrate dissolves gradually in
20 mL of water, is slightly soluble in ethanol and practically insoluble in ether.
Calcium Lactate Hydrate is partly efflorescent at ordi-
Assay Weigh accurately 0.5 g of Calcium Lactate Hydrate, previously dried, add water, dissolve by heating in
a water-bath, cool and add water to make exactly 100 mL.
Pipet 20 mL of this solution, add 80 mL of water and 1.5
mL of 8 mol/L potassium hydroxide TS and allow to
stand for 3 to 5 minutes. Add 0.1 g of NN indicator and
titrate immediately with 0.02 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution
changes from red to blue.
Each mL of 0.02 mol/L disodium ethylenediaminetetraacetate VS = 4.3644 mg of C6H10CaO6.
Calcium p-aminosalicylate
Hydrate
COOO2 Ca2+
NH2
Pas-calcium
7H2O
C7H5CaNO33H2O: 251.23
Calcium p-aminosalicylate Hydrate contains not less

than 97.0% and not more than 103.0% of calcium paminosalicylic acid (C7H5CaNO3: 191.20), calculated on
Description Calcium p-aminosalicylate Hydrate is a
white to slightly colored powder, is odorless and has a
slightly bitter taste.
Calcium p-aminosalicylate Hydrate is very slightly soluble in water and practically insoluble in ethanol, in acetone or in chloroform.
A saturated solution of Calcium p-aminosalicylate Hydrate is alkaline.
Identification
(1) To 50 mg of Calcium paminosalicylate Hydrate, add 100 mL of water, shake
well and filter. To 10 mL of the filtrate, add 1 mL of 1
mol/L hydrochloric acid TS, shake and add 1 drop of ferric chloride TS: a red-purple color develops.
(2) Determine the infrared spectra of Calcium paminosalicylate Hydrate and calcium p-aminosalicylate
Hydrate RS, as directed in the potassium bromide disk
method under the Infrared Spectro-photometry: both
same wavenumbers.
(3) To 3 g of Calcium p-aminosalicylate Hydrate, add
15 mL of ammonium chloride TS and 15 mL of water,
heat on a water-bath for 10 minutes: the solution responds to the Qualitative Tests 1), 2) and 3) for calcium
salt.
Purity (1) ChlorideDissolve 1.0 g of Calcium paminosalicylate Hydrate in 15 mL of dilute nitric acid
and add water to make 50 mL. Perform the test using this
more than 0.025%).
(2) Heavy metalsProceed with 1.0 g of Calcium paminosalicylate Hydrate according to method 3 and perform the test. Prepare the control solution with 2.0 mL of
(3) ArsenicDissolve 0.40 g of Calcium paminosalicylate Hydrate in 20 mL of 0.1 mol/L hydrochloric acid TS by warming on a water-bath, use this solu-
tion as the test solution and perform the test (not more
than 5 ppm).
(4) m-AminophenolTo 0.10 g of Calcium paminosalicylate Hydrate, add 5 mL of 0.1 mol/L disodium ethylenediaminetetraacetate TS, previously cooled
in ice-water and dissolve by shaking vigorously. Add
immediately 3 mL of ammonia-ammonium chloride buffer solution, pH 11.0, previously cooled in ice-water and
shake. Add 2 mL of 4-amino-N,N-diethylaniline sulfate
TS, shake, add 10.0 mL of cyclohexane and 4 mL of diluted potassium ferricyanide TS (1 in 10) and shake immediately for 20 seconds. Centrifuge this solution, wash
the separated cyclohexane layer with two 5 mL volumes
of diluted ammonia TS (1 in 14), add 1 g of anhydrous
sodium sulfate, shake and allow to stand for 5 minutes:
the clear cyclohexane layer has no more color than the
Control solutionDissolve 50 mg of maminophenol in water and dilute with water to make exactly 500 mL. Measure exactly 20 mL of this solution
and add water to make exactly 100 mL. Take 5.0 mL of
this solution, add 3 mL of ammonia-ammonium chloride
buffer solution, pH 11.0, previously cooled in ice-water
and treat this solution in the same manner as the test solution.
Water Between 23.3% and 26.3% (0.1 g, volumetric
titration, direct ditration)
Assay Weigh accurately about 0.2 g of Calcium paminosalicylate Hydrate, dissolve in 60 mL of water and
0.75 mL of dilute hydrochloric acid by warming on a water-bath. After cooling, add water to make exactly 100
mL and use this solution as the test solution. Measure
exactly 30 mL of the test solution, transfer to an iodine
flask and add exactly 25 mL of 0.05 mol/L bromine VS
and 20 mL of a solution of potassium bromide (1 in 4).
Add immediately 14 mL of a mixture of glacial acetic
acid and hydrochloric acid (5 : 2), stopper the flask immediately and allow to stand for 10 minutes with occasional shaking. Add cautiously 6 mL of potassium iodide
TS and shake gently. After 5 minutes, titrate the produced iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS). Perform a blank determination and make any necessary connection.
Each mL of 0.05 mol/L bromine VS
= 3.187 mg of C7H5CaNO3
tight containers.
KP 9 149
Calcium p-aminosalicylate
Granules
Pas-calcium Granules
Calcium p-aminosalicylate Granules contain not less
amount of calcium p-aminosalicylate hydrate
(C7H5CaNO33H2O: 254.25).
Granules, with Calcium p-aminosalicylate Hydrate.
Identification
Powder Calcium p-aminosalicylate
Granules, weigh a portion of the powder, equivalent to
50 mg of calcium p-aminosalicylate Hydrate according
to the labeled amount, add 100 mL of water, mix well
and filter. To 10 mL of the filtrate, add 1 mL of 1 mol/L
hydrochloric acid TS, shake and add 1 drop of ferric
chloride TS: a red-purple color develops.
Uniformity of Dosage Unit (divided)
quirement.
It meets the re-
Assay Powder Calcium p-aminosalicylate Granules,

weigh accurately a portion of the powder, equivalent to
about 0.4 g of calcium p-aminosalicylate hydrate
(C7H5CaNO33H2O: 251.23), add 120 mL of water and
1.5 mL of dilute hydrochloric acid and dissolve by heating on a water-bath. After cooling, add water to make exactly 200 mL and filter. Pipet 30 mL of the filtrate, transfer to an iodine flask and proceed as directed in the Assay under Calcium p-aminosalicylate Hydrate.
= 4.238 mg of C7H5CaNO33H2O
Calcium Pantothenate
HO
CH2
CH3 OH
CH3 H
2+
NHCH 2CH2CO2
Description Calcium Pantothenate is a white powder,

is odorless and has bitter taste.
Calcium Pantothenate is freely soluble in water, very
slightly soluble in ethanol and practically insoluble in
ether.
Calcium Pantothenate is hygroscopic.
pHThe pH of a solution of Calcium Pantothenate
Identification (1) Dissolve 50 mg of Calcium Pantothenate in 5 mL of sodium hydroxide TS and filter. Add 1
drop of copper(II) sulfate TS to the filtrate: a deep blue
color develops.
(2) Add 5 mL of sodium hydroxide TS to 50 mg of
Clacium Pantothenate, and boil for 1 minute. After cooling, add diluted hydrochloric acid (1 in 10) to adjust the
solution to a pH between 3 and 4, and add 2 dops of
iron(III) chloride TS: a yellow color develops.
(3) A solution of Calcium Panthothenate (1 in 10) responds to the Qualitative Tests for calcium salt.
-28.5 (after drying, 1 g, water, 20 mL, 100 mm).
g of Calcium Pantothenate in 20 mL of water: the solution is clear and colorless.
Pantothenate according to method 1 and perform the test.
(3) AlkaloidsDissolve 50 mg of Calcium Pantothenate in 5 mL of water, add 0.5 mL of hexaammonium
heptamolybdate TS and 0.5 mL of a solution of phosphoric acid (1 in 10): no white turbidity is produced.
hours).

tight containers.
Calcium Pantothenate, when dried, contains not less than

5.7% and not more than 6.0% of nitrogen (N: 14.01) and
not less than 8.2% and not more than 8.6% of calcium
(Ca: 40.08).
Ca
2
C18H32CaN2O10 : 476.53
Assay (1) NitrogenProceed with about 50 mg of

Calcium Pantothenate, previously dried and accurately
weighed, as directed under Nitrogen Determination.
(2) CalciumWeigh accurately about 0.4 g of Calcium Pantothenate, previously dried, and dissolve in 30
mL of water by warming. After cooling, add exactly 25
mL of 0.05 mol/L disodium ethylenediamine tetraacetate
VS, then 10 mL of ammonia-ammonium chloride buffer
solution, pH 10.7, and tittrate the excess disodium ethylenediamine tetraacetate with 0.05 mol/L magnesium
chloride VS until the color of the solution changes from
blue-purple to red-purple (indicator: 40 mg of eriochrome black T-sodium chloride indicator). Perform a

Each mL of 0.05 mol/L disodium ethylenediamine tetraacetate VS = 2.0039 mg Ca
Calcium Polystyrene Sulfonate

Calcium Polystyrene Sulfonate is a cation exchange resin
prepared as the calcium form of the sulfonated styrene
divinylbenzene copolymer.
Calcium Polystyrene Sulfonate, when dried, contains not
less than 7.0% and not more than 9.0% of calcium (Ca:
40.08).
Each g of Calcium Polystyrene Sulfonate, when dried,
exchanges with 53 to 71 mg of potassium (K: 39.10).
Description Calcium Polystyrene Sulfonate is a pale
yellowish white to pale yellow powder, is odorless and
tasteless.
Calcium Polystyrene Sulfonate is practically insoluble in
water, in ethanol or in ether.
Identification (1) Take Calcium Polystyrene Sulfonate
and Calcium Polystyrene Sulfonate RS, previously dried
and determine the infrared spectra as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) Mix 0.5 g of Calcium Polystyrene Sulfonate with
10 mL of dilute hydrochloric acid, filter and neutralize
the filtrate with ammonia TS: the solution responds to
the Qualitative Tests for calcium salt.
Purity (1) AmmoniumPlace 1.0 g of Calcium Polystyrene Sulfonate in a flask, add 5 mL of sodium hydroxide TS, cover the flask with a watch glass having a moistened strip of red litmus paper on the underside and boil
for 15 minutes: the gas evolved does not change the red
litmus paper to blue (not more than 5 ppm).
Polystyrene Sulfonate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
Calcium Polystyrene Sulfonate according to Method 3
(4) StyreneTo 10.0 g of Calcium Polystyrene Sulfonate, add 10 mL of acetone, shake for 30 minutes, centrifuge and use the supernatant as the test solution. Separately, dissolve 10 mg of styrene in acetone to make exactly 100 mL. Pipet 1 mL of this solution, dilute with
acetone to make exactly 100 mL and use this solution as
the test solution and the standard solution as directed under the Gas Chromatography according to the following
conditions. Determine the peak heights, HT and HS, of

styrene for the test solution and the standard solution: HT
is not larger than HS.
Column: A stainless steel column, about 3 mm in inside diameter and about 2 m in length, having polyethylene glycol 20M coated at the ratio of 15% on siliceous
earth for gas chromatography (149 to 177 m in particle
diameter).
about 90 C.
time of styrene is about 9 minutes.
System suitability
peak of styrene is not less than 800 and the symmetry
factor of the peak is between 0.8 and 1.2.
each peak height of styreme is not more than 5.0%.
(5) SodiumPipet 20 mL of the 50 mL solution obtained in Assay (1), add 0.02 mol/L hydrochloric acid to
make exactly 500 mL and use this solution as the test solution. Separately, weigh accurately 0.2542 g of sodium
chloride, previously dried at 130 C for 2 hours and dissolve in 0.02 mol/L hydrochloric acid to make exactly
1000 mL. Pipet a suitable volume of this solution and dilute with 0.02 mol/L hydrochloric acid to make a solution containing 1 to 3 g of sodium (Na: 22.99) per mL
and use these solutions as the standard solutions. Perform
the test with the test solution and the standard solutions
as directed under the Atomic Absorption Spectrophotometry according to the following conditions and determine the amount of sodium in the test solution using the
calibration curve obtained from the standard solutions:
the amount of sodium is not more than 1%.
Gas used: Combustible gas: Acetylene.
Supporting gas: Air.
Lamp: A sodium hollow-cathode lamp.
80 C, 5 hours).
Microparticles (1) Apparatus: Use an apparatus as
shown in the figure.
Actual volume to the mark of 20 cm at which the sedimentation tube is inserted: 550 mL.
Single suction volume: 10 mL.
(2) Procedure: Weigh accurately about 5.5 g of Calcium Polystyrene Sulfonate, previously dried, add 300
KP 9 151
mL of water of 25 C and mix for 5 minutes. Transfer
this turbid solution to the sedimentation tube, J, keeping
a temperature at 25 C, add water of 25 C to 2 mm below the mark, F of 20 cm of the sedimentation tube, J
and then insert the pipet. Open the two-way stopcock, C,
exhaust air, add exactly water from the vent-hole, D to
the mark, F of 20 cm and close the two-way stopcock, C.
Shake the apparatus well vertically and horizontally, disperse Calcium Polystyrene Sulfonate in water and then
open the two-way stopcock and allow to stand at 25 1
C for 5 hours and 15 minutes. Then, draw exactly the
meniscus of the turbid solution in sedimentation tube, J,
up to the mark of pipet bulb, A, by suction, open the twoway stopcock, C, to the outlet of pipet, H and transfer
exactly measured 20 mL of the turbid solution to a
weighing bottle. Repeat the procedure and combine exactly measured 20 mL of the turbid solution. Evaporate
20 mL of this turbid solution on a water-bath to dryness,
dry to constant mass at 105 C and weigh the residue as
WS (g). Pipet 20 mL of used water and weigh the residue
in the same manner as WB (g). Calculate the difference
mi (g) of the weight between WS and WB and calculate
the amount of microparticles (S) by the following equation: the amount of microparticles is not more than 0.1%.
|WS - WB| (g) V (mL)
S (%) = 20 (mL) amount of sample (g) 100
V: Actual volume (mL) to the mark of 20 cm at which
the suction part of pipet is inserted.
A: Mark of pipet bulb,

B: Pipet bulb for suction,
C: Two-way stopcock,
D: Vent-hole,
E: Suction part of pipet,
F: Mark of 20 cm,
G: Base line of 0 cm,
H: Outlet of pipet,
I: Capillary tube of pipet,
J: Sedimentation tube.
fer the mixture and wash out completely with the aid of a
small volume of 3 mol/L hydrochloric acid TS, to a column, 12 mm in inside diameter and 70 mm in length,
packed with a pledged of fine glass wool in the bottom,
placing a volumetric flask as a receiver under the column.
Then collect about 45 mL of eluate, adding 3 mol/L hydrochloric acid TS to the column and add water to make
exactly 50 mL. Pipet 20 mL of this solution, adjust with
ammonia water to a pH of exactly 10. Titrate immediately with 0.05 mol/L disodium ethylenediaminetetraacetate
VS until the red-purple color of the solution disappears
and a blue color is observed (indicator: 40 mg eriochrome black T-sodium chloride indicator). Perform a
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 2.0039 mg of Ca
(2) Potassium exchange capacityPipet 50 mL of
standard potassium stock solution into a glass-stoppered
flask containing about 1.0 g of dried Calcium Polystyrene Sulfonate, accurately weighed, stir for 120 minutes,
filter and discard the first 20 mL of the filtrate. Pipet 5
mL of the subsequent filtrate and add 0.02 mol/L hydrochloric acid TS to make exactly 100 mL. Pipet 10 mL
of this solution, add 0.02 mol/L hydrochloric acid TS to
make exactly 1000 mL and use this solution as the test
solution. Separately, measure exactly a suitable volume
of standard potassium stock solution, dilute with water to
make solutions containing 0.5 to 2.5 g of potassium (K:
39.10) per mL and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Atomic Absorption
Spectrophotometry according to the following conditions
and determine the amount, Y (mg), of potassium in 1000
mL of the test solution, using the calibration curve obtained from the standard solution. The exchange capacity
for potassium per g of dried Calcium Polystyrene Sulfonate is 53 to 71 mg, calculated by the following equation.
Exchange capacity (mg) for potassium (K) per g of dried
X - 100Y
Calcium Polystyrene Sulfonate =
W
X: Amount (mg) of potassium in 50 mL of standard
potassium stock solution before exchange,
W: Amount (g) of dried Calcium Polystyrene Sulfonate taken.
Gas used: Combustible gas- Acetylene.
Lamp: A potassium hollow-cathode lamp.
Andreagen pipet
Assay (1) CalciumWeigh accurately about 1.0 g of
Calcium Polystyrene Sulfonate, previously dried, and
disperse in 5 mL of 3 mol/L hydrochloric acid TS. Trans-
d-Camphor
H3C
O
CH3
CH3
C10Hl6O: 152.23
d-Camphor contains not less than 96.0% and not more
than 101.0 % of d-camphor (C10Hl6O).
Description d-Camphor is a colorless or white, translucent crystal, crystalline powder or mass. d-Camphor
has a characteristic, agreeable odor and a slightly bitter
taste, followed by a pleasant, cooling sensation.
Camphor is freely soluble in ethanol, in ether or in carbon disulfide and slightly soluble in water.
d-Camphor slowly volatilizes at room temperature.
Identification Dissolve 0.1 g of d-Camphor in 2 mL of
methanol, add 1 mL of 2,4-dinitrophenylhydrazine TS
and heat for 5 minutes in a water-bath: an orange-red
D : Between + 41.0
and + 43.0 (5g, ethanol, 50 mL, 100 mm).
Melting Point
Purity (1) WaterShake 1.0 g of d-Camphor with 10

mL of carbon disulfide: the solution is clear.
(2) Chlorinated compoundsMix 0.20 g of finely
powdered d-Camphor with 0.4 g of sodium peroxide in a
dried, porcelain crucible. Heat the crucible gently by the
open flame until the incineration is complete. Dissolve
the residue in 20 mL of warm water, acidify with 12 mL
of dilute nitric acid and filter the solution into a Nessler
tube. Wash the test tube and the filter with three 5 mL
volumes of hot water, adding the washings to the filtrate.
After cooling, add water to make 50 mL, then add 1 mL
of silver nitrate TS, mix well and allow to stand for 5
minutes: the turbidity of the solution does not exceed that
of the following control solution.
Control solutionPrepare in the same manner as described above, using 0.20 mL of 0.01 mol/L hydrochloric
acid VS.
d-Camphor RS, add exactly 5 mL each of the internal

standard solution, dissolve in dehydrated methanol to
make 100 mL and use these solutions as the test solution
and the standard solution, respectively. Perform the test
with 2 L each of the test solution and the standard solution as directed under the Gas Chromatography according to the following conditions and calculate the ratios,
QT and QS , of the peak area of d-Camphor to that of
the internal standard for the test solution and the standard
Amount (mg) of d-camphor (C10Hl6O)
= amount (mg) of d-Camphor RS QT
QS
Internal standard solutionA solution of methyl salicilate in dehydrated ethanol (1 in 25).

Column: A column, about 3 mm in inside diameter
and 3 m in length, packed with 10% of polyethylene glycol 20M for gas chromatography supported on 180 to
250 m mesh silanized siliceous earth for gas chromatography.
about 160 C.
time of d-Camphor is about 6 minutes.
System suitability
with 2 L of the standard solution under the above operating conditions, d-Camphor and the internal standard
are eluted in this order, with a resolution between these
the ratios of the peak area of d-Camphor to that of the internal standard is not more than 1.0 %.
dl-Camphor
H3C
O
CH3
CH3
(3) Non-volatile residueHeat 2.0 g of d-camphor

in a water-bath until sublimation is completed, then dry
the residue at 105 C for 3 hours: the weight of the residue is not more than 1.0 mg.
and enantiomer
Assay Weigh accurately 0.1 g each of d-Camphor and
dl-Camphor contains not less than 96.0% and not more
C10Hl6O: 152.23
KP 9 153
than 101.0% of dl-camphor (C10Hl6O).
Description dl-Camphor is a colorless or white, translucent crystal, crystalline powder or mass. dl-Camphor
has a characteristic, agreeable odor and has a slightly bitter taste followed by a pleasant, cooling sensation.
dl-Camphor is freely soluble in ethanol, in ether or in
carbon bisulfide and slightly soluble in water.
dl-Camphor slowly volatilizes at room temperature.
Identification Dissolve 0.1 g of dl-Camphor in 2 mL
of methanol, add 1 mL of 2,4-dinitrophenyl-hydradine
TS and heat for 5 minutes in a water-bath: an orange-red
D : Between - 1.5 and
+ l.5 (5 g, ethanol, 50 mL, 100 mm).
Melting Point
Purity (1) WaterShake 1.0 g of dl-Camphor with 10

mL of carbon bisulfide: the solution is clear.
(2) Chlorinated compoundsMix 0.20 g of finely
powdered dl-Camphor with 0.4 g of sodium peroxide in
a dried, porcelain crucible. Heat the crucible gently by
the open flame until the incineration is complete. Dissolve the residue in 20 mL of warm water, acidify with
12 mL of dilute nitric acid and filter the solution into a
Nessler tube. Wash the test tube and the filter with three
5 mL volumes of hot water, adding the washings to the
filtrate. After cooling, add water to make 50 mL, then
add 1 mL of silver nitrate TS, mix well and allow to
stand for 5 minutes: the turbidity of the solution does not
exceed that of the following control solution.
Control solutionPrepare in the same manner as described above, using 0.20 mL of 0.01 mol/L hydrochloric
acid VS.
(3) Non-volatile residueHeat 2.0 g of dl-Camphor
in a water-bath until sublimation is completed, then dry
the residue at 105 C for 3 hours: the weight of the residue is not more than 1.0 mg.
Assay Weigh accurately 0.1 g each of dl-Camphor and
dl-Camphor RS, add exactly 5 mL each of the internal
standard solution, dissolve in dehydrated methanol to
with 2 L each of the test solution and the standard solution as directed under the Gas Chromatography according to the following conditions and calculate the ratios,
QT and QS , of the peak area of dl-camphor to that of
Amount (mg) of dl-camphor (C10Hl6O)
= amount (mg) of dl-Camphor RS
QT
QS
Internal standard solutionA solution of methyl salicilate in dehydrated ethanol (1 in 25).

and about 3 m in length, packed with 10% of polyethylene glycol 20M for gas chromatography supported on
180 to 250 m mesh silanized siliceous earth for gas
chromatography.
Column temperature: A constant tem-perature of
about 160 C.
time of dl-Camphor is about 6 minutes.
System suitability
with 2 L of the standard solution under the above operating conditions, dl-Camphor and the internal standard
are eluted in this order, with a resolution between these
the ratios of the peak area of dl-Camphor to that of the
internal standard is not more than 1.0 %.
Captopril
H
CH3
HS
H
O
OH
C9H15NO3S : 217.29
Captopril contains not less than 97.5% and not more than
102.0% of captopril (C9H15NO3S), calculated on the
dried basis.
Description Captopril is white crystal or crystalline
powder.
Captopril is very soluble in methanol, freely soluble in
ethanol and soluble in water.
Melting pointsAbout 106 C
Identification Determine the infrared spectra of Captopril and Captopril RS, previously dried, as directed in

-134
mm)
[ ]20
D :
Between -125
and
(dried, 0.1 g, dehydrated ethanol, 10 mL, 100
Purity (1) Heavy metalsProceed with 1 g of Captopril according to the Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(2) ArsenicPrepare the test solution with 1 g of
Captopril according to Method 1 and perform the test.
(3) Related substancesDissolve 50.0 mg of Captopril in methanol to make exactly 25 mL and use this solution as the test solution(use immediately after preparation). Separately, weigh accurately captopril disulfide RS,
dissolve in methanol to make 10 g per mL and use this
20 L each of these solutions as directed under the Liquid Chromatography according to the following conditions and calculate the peak area, AT and AS , of captopril disulfide of these solutions: the amount of captoprile
disulfide is not more than 1.0% and the peak response of
each impurity is not more than 40% of the main peak in
the chromatogram of the standard solution(not more than
0.2%) and the sum of the impurity peak responses is not
more than the main peak response in the chromatogram
of the standard solution(not more than 0.5%).
Amount (%) of captopril disulfide =
C S AT
100
C u AS
CS: the concentration of captopril disulfide RS in the

standard solution (g/mL)
Cu: the concentration of captopril in the test solution
(g/mL)
Detector: An ultraviolet absorption photometer ( wavelength: 220 nm ).
diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m to 10
m in particles diameter ).
Mobile phase: A mixture of tetrahydrofuran methanol
solution (9 in 100) and phosphoric acid solution (1 in
2000) (33 : 67).
Selection of column: Dissolve Captopril RS, Captopril Disulfide RS and 3-Acetylthio-2-Methylpropanoic
Acid RS in methanol to make 10 g per mL, respectively.
Proceed with 20 L of this solution under the above operating conditions. Use a column giving elution of captopril, 3-acetylthio-2-methylpropanoic acid and captopril
disulfide in this order with the resolution between peaks
of captopril and 3-acetylthio-2-methylpropanoic acid be-
ing not less than 3.0.

60 C, 3 hours).
Assay Weigh accurately about 0.3 g of Captopril, dissolve in 100 mL of water, add 20 mL of dilute sulfuric
acid and 1 g of potassium iodide and shake. Titrate with
1/60 mol/L potassium iodate VS (indicator: 2 mL of
starch TS). Perform a blank determination and make any
Each mL of 1/60 mol/L potassium iodate
= 21.729 mg of C9H15NO3S
Captopril Tablets
Captopril Tablets contain not less than 90.0% and not
more than 110.0% of labeled amount of captopril
(C9H15NO3S: 217.29).
Method of Preparation Prepare as directed under Tablets, with Captopril.
Identification weigh accurately and Powder a portion
of Captopril Tablets, equivalent to 0.1 g of Captopril, put
in the flask, add 25 mL of methanol, mix, centrifuge and
use the supernatant as the test solution. Separately weigh
a suitable amount of Captopril RS, dissolve in a suitable
amount of methanol so as to contain 4 mg of Captopril
solution as directed under Thin Layer Chromatograph.
Spot 50 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plates with a mixture of toluene, glacial
acetic acid and methanol (75 : 25 : 1) to a distance of
about 15 cm and air-dry the plate. Spray with a freshly
prepared mixture of ammonium hydroxide and a solution
of 0.04 % 5,5-dithio-bis-(2-nitrobenzoic acid) (1 : 6).
The Rf value of the principal spot of the test solution is
the same as that of standard solution.
Related Substances CaptoprilndisulfideUse the test
solution under the Assay. Separately, weigh accurately a
suitable portion of Captopril Disulfide RS and dissolve
in a suitable volume of mobile phase so as to contain 50
g of captopril disufide per mL. Use this solution as the
standard solution. Avoid the test solution and the standard solution with contact of air and use them within 8
hours of preparation. Perform the test with 20 L each of
the test solution and the standard solution as directed un-
KP 9 155
der the the Liquid Chromatography according to the following operating conditions. Determine peak areas, AT
and AS , of captopril disulfide of the test solution and
the standard solution, respectively: the amount of captopril disulfide is not more than 3.0%.
A
Amount (%) of captopril disulfide = 2500 C T
W
AS
C: Concentration of the standard solution (mg/mL),

W: Amount of sample (mg).
Column:A stainless steel column, about 4.6 mm in
octadecylsilylated silica gel (contains 15% of CH group)
for liquid chromatography (3 to 10 m in particle diameter).
Mobile phase: A mixture of methanol, water and
phosphoric acid (450 : 550 : 0.5).
System suitability
with 20 L of the standard solution, as directed under the
above operating conditions, Captopril and captopril disulfide are eluted in this order with the resolution between
these peaks being not less than 2.0.
times with with 20 L of the standard solution, as directed under the above operating conditions, the relative
standard deviation between the peak areas of captopril is
not more than 2.0%.
Dissolution Test Perform the test with 1 tablet of Captopril Tablets at 50 revolutions per minute according to
Method 1 under Dissolution Test, using 900 mL of 0.01
mol/L hydrochloric acid. as a dissolution solution. Take
20 mL or more of the dissolved solution 20 minutes after
starting the test, filter and use the filtrate as the test solution. Separately, weigh accurately a suitable amount of
Captopril RS, dissolved in a suitable amount of water so
as to contain same amount of Captopril per mL as the
test solution and use this solution as the standard solution.
Determine the absorbances of the test solution and the
standard solution at 212 nm as directed under the Ultraviolet-visible Spectrophotometry : The dissolution rate
(%) with respect to the labeled amount of Captopril Tablets in 20 minutes is not less than 80%.
tively and stepwise if necessary, with mobile phase to

obtain a solution having a concentration of about 1 mg of
Captopril per mL. Separately, dissolve suitable quantities
of Captopril RS and Captopril Disulfide RS in mobile
phase to obtain a solution having known concentrations
of about 1 mg per mL and 50 g per mL, respectively.
Use this solution as the standard solution. Avoid the test
solution and the standard solution with contact of air and
use them within 8 hours of prepration. Proceed with 20
L each of the test solution and the standard solution according to the Liquid Chromatography under the following operating conditions. Determine peak areas, AT and
AS , of Captopril of the test solution and the standard solution, respectively.

Amount(mg) of Captopril (C9H15NO3S)
in 1 mL of test solution = C
C: Concentration (mg/mL) of Captopril in the standard solution,

inside diameter and about 25 cm length, packed with octadecylsilylated silica gel (contains 15% of CH group)
for liquid chromatography (5 to 10 m in particle diameter).
Mobile phase: A mixture solution of methanol, water
and phosphoric acid (450 : 550 : 0.5).
System suitability
with 20 L of the stndard solution, as directed under the
above operating conditions, Captopril and captopril disulfide are eluted in this order with the resolution between
times with 20 L of the standard solution, as directed
under the above operating conditions, the relative standard deviation of the peak areas of Captopril is not more
than 2.0%.
Carbamazepine

Assay Transfer not less than 20 Captopril Tablets to a
suitable volumetric flask, add mobile phase to fill the
flask to about half of its capacity and sonicate for 15 minutes. Dilute with mobile phase to volume, shake by mechanical means for 15 minutes and filter. Dilute quantita-
AT
AS
N
C
O
NH2
C15Hl2N2O: 236.27
Carbamazepine, when dried, contains not less than
97.0% and not more than 103.0% of carbamazepine
(C15Hl2N2O)
Description Carbamazepine is a white to slightly yellowish white powder, is odorless and tasteless at first and
leaves a slightly bitter aftertaste.
Carbamazepine is freely soluble in chloroform, sparingly
soluble in ethanol or in acetone and very slightly soluble
in water or in ether.
Identification (1) To 0.1 g of Carbamazepine, add 2
mL of nitric acid and heat in a water-bath for 3 minutes:
an orange-red color is produced.
(2) To 0.1 g of Carbamazepine, add 2 mL of sulfuric
acid and heat in a water-bath for 3 minutes: a yellow color is produced with a green fluorescence.
(3) Examine Carbamazepine under ultraviolet light:
the solution shows an intense blue fluorescence.
Carbamazepin and Carbamazepin RS in ethanol (1
10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
Melting Point

plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of toluene and methanol (19 :
Spray evenly potassium bichromate-sulfuric acid TS on
the plate: the spots other than the principal spot from the
standard solution.
hours).
Assay Dissolve 50 mg of Carbamazepine, previously
dried and accurately weighed, in ethanol to make exactly
250 mL. Dilute 5 mL of this solution with ethanol to
make exactly 100 mL. Perform the test as directed under
the Ultraviolet-visible Spectrophotometry and determine
the absorbance, A, of this solution at the wavelength of a
maximum absorption at about 285 nm.
Amount (mg) of carbamazepine (C15H12N2O)
A
= 490 50000

g of Carbamazepine in 10 mL of chloroform: the solution
is clear and colorless to pale yellow.
(2) AcidTo 2.0 g of Carbamazepine, add exactly 40
mL of water, stir well for 15 minutes and filter through a
glass filter. To 10 mL of this filtrate, add 1 drop of phenolphthalein TS and 0.50 mL of 0.01 mol/L sodium hydroxide VS: a red color is produced.
(3) AlkaliTo 10 mL of the filtrate obtained in (2),
add 1 drop of methyl red TS and 0.50 mL of 0.01 mol/L
hydrochloric acid VS: a red color is produced.
(4) ChlorideDissolve 0.25 g of Carbamazepine in
30 mL of acetone, add 6 mL of dilute nitric acid and water to make 50 mL and perform the test using this solution as the test solution. Prepare the control solution as
follows: to 0.20 mL of 0.01 mol/L hydrochloric acid VS,
(5) Heavy metalsProceed with 2.0 g of Carbamazepine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(6) Related substancesDissolve 0.25 g of Carbamazepine in 10 mL of chloroform and use this solution
as the test solution. Separately, dissolve 5.0 mg of iminodibenzyl in chloroform to make exactly 100 mL and
Carbazochrome Sodium
Sulfonate hydrate
CH3
O
SO3Na
H
3H2O
H2NCONHN
and enantiomer
Carbazochrome Sodium Sulfonate
C10Hl1N4NaO5S 3H20 : 376.32
Carbazochrome Sodium Sulfonate Hydrate contains not
less than 98.0% and not more than 102.0% of carbazochrome sodium sulfonate (C10Hl1N4NaO5S: 322.28), calculated on the anhydrous basis.
Description Carbazochrome Sodium Sulfonate is a
orange-yellow, crystal or crystalline powder.
Carbazochrome Sodium Sulfate is sparingly soluble in
water, very slightly soluble in ethanol and practically insoluble in ether.
A solution of Carbazochrome Sodium Sulfonate(1 in
solutions of Carbazochrome Sodium Sulfonate and Car-
KP 9 157
bazochrome Sodium Sulfonate RS (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Carbazochrome
Sodium Sulfonate and Carbazochrome Sodium Sulfonate
(3) A solution of Carbazochrome Sodium Sulfonate
(1 in 100) responds to the Qualitative Tests (1) for sodium salt.
pH Dissolve 0.8 g of Carbazochrome Sodium Sulfonate in 50 mL of water by warming and cool: the pH of
this solution is between 5.0 and 6.0.
g of Carbazochrome Sodium Sulfonate in 50 mL of water by wanting and allow to cool: the solution is clear.
Perform the test with this solution as directed under the
Ultraviolet-visible Spectrophotometry: the absorbance at
590 nm is not more than 0.070.
(2) Heavy metalsProceed with 1.0 g of Carbazochrome Sodium Sulfonate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
(3) Related substancesDissolve 50 mg of Carbazochrome Sodium Sulfonate in 100 mL of water and use
solution, add water to make exactly 200 mL and use this
the test solution and the standard solution by the automatic integration method: the total area of the peaks other than the peak of carbazochrome sulfonate from the test
solution is not larger than the peak area of carbazochrome sulfonate from the standard solution.
about 40 C.
Mobile phase: Dissolve 1.2 g of monobasic ammonium phosphate in 1000 mL of water and filter through a
membrane filter, if necessary. To 925 mL of this solution,
add 75 mL of ethanol, shake and adjust with phosphoric
acid to a pH of 3.
time of carbazochrome sulfonate is between 6 and 8 minutes.
System suitability
Test for required detectability: Take exactly 2
mLof the standard solution, add the mobile phase to
make exactly 20 mL. The peak area of Carbazochrome
Sulfonate from 10 mL of this solution is 7% to 13% of
the peak area of Carbazochrome Sulfonate from the
standard solution.
System performance: Dissolve 10 mg each of Carbazochrome Sodium Sulfonate and carbazochrome in
100 mL of water by warming. When the procedure is run
conditions, Carbazochrome sulfonate and Carbazochrome are eluted in this order with the resolution between
their peaks being not less than 3.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of carbazochrome sulfonate
obtained from 10 L of the standard solution composes
about 5% of the full scale.
the retention time of carbazochrome sulfonate after the
solvent peak.
titration, direct titration).
Assay Weigh accurately about 0.25 g of Carbazochrome Sodium Sulfonate, dissolve in 50 mL of water, apply to a chromatographic column, 10 mm in diameter,
previously prepared with 20 mL of strongly acidic ion
exchange resin for column chromatography (type H) and
allow to flow at a rate of 4 mL per minute. Wash the column with 150 mL of water, combine the washing and the
former eluent solution and titrate with 0.05 mol/L sodium hydroxide VS (potentiometric titration, Endpoint
= 16.114 mg of C10H11N4NaO5S
L-Carbocysteine
H
HO 2CCH2SCH2
CO2H
NH 2
C5H9NO4S: 179.19
Carbocysteine
L-Carbocysteine,
when dried, contains not less than

98.5% and not more than 101.0% of L-carbocysteine
(C5H9NO4S).
Description
L-Carbocysteine
is a white crystalline

powder, is odorless and has a slightly acid taste.
L-Carbocysteine is very slightly soluble in water and
practically insoluble in ethanol, in glacial acetic acid or
in ether.
L-Carbocysteine dissolves in dilute hydrochloric acid or
in sodium hydroxide TS.
Identification (1) To 0.2 g of L-Carbocysteine, add 1
mL of lead acetate TS and 3 mL of water, shake, add 0.2
g of sodium hydroxide and heat over a flame for 1
minute: a dark brown to black precipitate is formed.
(2) Determine the infrared absorption spectra of LCarbocysteine and Carbocysteine RS as directed in the
D : Between -33.5 C
and -36.5 C. Weigh accurately 5 g of L-Carbocysteine,
previously dried, dissolve in 20 mL of water and a suitable volume of a solution of sodium hydroxide (13 in 100)
and adjust the pH with 1 mol/L hydrochloric acid TS or
0.1 mol/L hydrochloric acid TS to 6.0 and add water to
make exactly 50 mL. Determine the optical rotation of
this solution in a 100 mm cell.
g of L-Carbocysteine in 10 mL of a solution of sodium
hydroxide TS: the solution is clear and colorless.
(2) ChlorideDissolve 0.20 g of L-Carbocysteine in
10 mL of water and 20 mL of nitric acid and add water to
test solution.
Control solutionTo 0.40 mL of 0.01 mol/L hydrochloric acid VS, add 20 mL of nitric acid and water to
(3) AmmoniumPerform the test with 0.25 g of LCarbocysteine using the distillation under reduced pressure. Prepare the control solution with 5.0 mL of standard ammonium solution (not more than 0.02%).
(4) Heavy metalsProceed with 1.0 g of LCarbocysteine according to Method 2 and perform the
L-Carbocysteine according to Method 3 and perform the
(6) Related substancesDissolve 0.30 g of LCarbocysteine in 10 mL of 0.2 mol/L sodium hydroxide
TS and use this solution as the test solution. Pipet 2 mL
of the test solution and add 0.2 mol/L sodium hydroxide
TS to make exactly 100 mL. Pipet 1 mL of this solution
and add 0.2 mol/L sodium hydroxide TS to make exactly
10 mL and use this solution as the standard solution. Per-
form the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solution, in 15 mm length along the starting line on a plate of
plate with a mixture of n-butanol, water and glacial acetic acid (3 : 1 : 1) to a distance of about 10 cm, air-dry the
plate and then dry at 100 C for 30 minutes. Spray evenly
a solution of ninhydrin in acetone (1 in 50) on the plate
and heat at 80 C for 5 minutes: the spots other than the
hours).
Assay Weigh accurately 0.25 g of L-Carbocysteine,
previously dried, dissolve in exactly 20 mL of 0.1 mol/L
perchloric acid VS and 50 mL of glacial acetic acid and
titrate the excess perchloric acid with 0.1 mol/L sodium
acetate VS (potentiometric titration, Endpoint Detection
Method in Titrimetry). Perform a blank determination
= 17.919 mg of C5H9NO4S
Packaging and Storagte Preserve in tight containers.
Carbon Dioxide
CO2: 44.01
Carbon Dioxide contains not less than 99.5% and not
more than 101.0 vol% of carbon dioxide (CO2).
Description Carbon Dioxide is a colorless gas at room
temperature and under atmospheric pressure and is odorless.
1 mL volume of Carbon Dioxide dissolve in 1 mL of water and the solution is slightly acidic.
1000 mL of Carbon Dioxide at 0 C and under a pressure
of 101.3 kPa weighs about 1.978 g.
Identification (1) Put a flaming wood splinter into
Carbon Dioxide: the flame is extinguished immediately.
(2) Pass Carbon Dioxide into calcium hydroxide TS:
a white precipitate is produced. Collect the precipitate
and add acetic acid: it dissolves with effervescence.
Purity Maintain containers of Carbon Dioxide between
18 C and 22 C for not less than 6 hours prior to the test
and correct the volume of Carbon Dioxide to 20 C and
under a pressure of 101.3 kPa.
(1) AcidPlace 50 mL of freshly boiled and cooled
KP 9 159
water in a Nessler tube and pass 1000 mL of Carbon
Dioxide for 15 minutes through an introducing tube
about 1 mm in diameter extending to 2 mm from the bottom of the Nessler tube, then add 0.10 mL of methyl
orange TS: the solution has no more color than the following control solution.
draw carrier gas into the mixer to make exactly 100 mL,
allow to mix thoroughly and use this mixture as the standard gas mixture. Perform the test with 1.0 mL of the
mixture in the same manner as directed in the case of
Carbon Dioxide and determine the peak area, AS, of nitrogen: AT is smaller than AS and no other peak appears.
Control solutionTo 50 mL of freshly boiled and

cooled water in a Nessler tube, add 0.10 mL of methyl
orange TS and 1.0 mL of 0.01 mol/L hydrochloric acid
VS.
Detector: A thermal-conductivity detector.
and about 3 m in length, packed with silica gel for gas
chromatography (300 to 500 m in particle diameter).
about 50 C.
Carrier gas: Hydrogen or helium.
time of nitrogen is about 2 minutes.
System suitability
System performance: Collect 0.5 mL of nitrogen in
a gas mixer, add Carbon Dioxide to make 100 mL, mix
well and proceed with 1.0 mL of the mixture under the
above operating conditions. Use a column giving wellresolved peaks of nitrogen and Carbon Dioxide in this
order.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of nitrogen obtained from 1.0
mL of the standard gas mixture composes about 50% of
the full scale.
(2) Hydrogen phosphide, hydrogen sulfide or reducing organic substancesPlace 25 mL of silver nitrateammonia TS and 3 mL of ammonia TS in each two Nessler tubes A and B and designate the solution in each tube
as solutions A and B, respectively. Pass 1000 mL of Carbon Dioxide into solution A in the same manner as directed in (1): the turbidity and color of this solution are
the same as that of solution B.
(3) Carbon monoxideIntroduce 5.0 mL of Carbon
dioxide into a gas-cylinder or a syringe for gas chromatography from a metal cylinder holding gas under pressure and fitted with a pressure reducing valve, through a
directly connected polyvinyl tube. Perform the test with
this according to the Gas Chromatography under the following conditions: no peak is observed at the same retention time as that of the carbon monoxide.
Detector: A thermal-conductivity detector.
Column: A column about 3 mm in inside diameter
and about 3 m in length, packed with 300 to 500 m zeolite for gas chromatography (0.5 nm in poreous size).
about 50 C.
Carrier gas: Hydrogen or helium.
time of carbon monoxide is about 20 minutes.
System suitability
System performance: To 0.1 mL each of carbon
monoxide and air in a gas mixer add carrier gas to make
100 mL and mix well. When the procedure is run with
5.0 mL of the mixed gas under the above operating conditions, oxygen, nitrogen and carbon monoxide are
eluted in this order with a well-resolving of their peaks.
Detection sensitivity: Adjust the sensitivity so that
the peak height of carbon monoxide obtained from 5.0
mL of the mixed gas used in the system performance is
about 10 cm.
(4) Oxygen and nitrogenIntroduce 1.0 mL of Carbon Dioxide into a gas-measuring tube or syringe for gas
chromatography from metal cylinder under pressure with
a pressure-reducing valve through a directly connected
polyvinyl chloride tube. Perform the test as directed under Gas Chromatography according to the following
conditions and determine the peak area, AT, of air. Separately, introduce 0.50 mL of nitrogen into the gas mixer,
Assay For the withdrawing of Carbon Dioxide, proceed as directed in the Purity. Place 125 mL of a solution
of potassium hydroxide (1 in 2) in a gas pipet of suitable
capacity. Measure exactly about 100 mL of Carbon Dioxide in a 100 mL gas buret filled with water. Force the
entire volume of gas into the gas pipet and shake for 5
minutes. Draw some of the unabsored gas into the gas
buret, measure the volume, force the residual back upon
the surface of the liquid in the gas pipet and repeat this
procedure until a constant volume of the residual reading
is obtained. Determine the volume, V (mL) of the residual gas and correct its volume, V to 20 C and under a
pressure of 101.3 kPa.
Volume (mL) of carbon dioxide (CO2)
= calculated volume (mL) of the sample
calculated volume, V (mL)
Packaging and Storage Preserve in pressure metal cylinders not exceeding 40 C.
Carboplatin
O
O
NH3
Pt
NH3
C6H12N2O4Pt : 371.25
Carboplatin contains not less than 98.0% and not more
than 102.0% of carboplatin (C6H12N2O4Pt), calculated on
Description Carboplatin is a white crystalline powder.
Carboplatin is slightly soluble in water, and practically
insoluble in acetone or in ethanol.
Melting pointabout 200 (decomposition)
Identification Determine the infrared spectra of Carboplatin and Carboplatin RS as directed in the potassium
pH pH of a solution of Carboplatin (1 in 100) is between 5.0 and 7.0.
g of carboplatin in water to make exactly 10 mL and determine the transmittance of this solution using water as
a blank as directed under the Ultraviolet-visible Spectrophotometry at the 440 nm: not less than 97%.
(2) Insoluble substancesTransfer about 1 g of carboplatin, accurately weighed, to a beaker. Add 100 mL
of water, and dissolve by stirring for 30 minutes. Filter
through a tared glass filter. Rinse the beaker with water,
and filter the rinsings. Dry the glass filter at 130 10 C
to constant mass: the amount of residue is not more than
0.5%.
(3) PlatinumTransfer about 0.25 g of Carboplatin,
accurately weighed, to a 600-mL beaker. Add 400 mL
of water, and slowly dissolve by heating almost to the
boiling point, stirring frequently with a glass rod. Dissolve it complately, boil for about 10 minutes, cool for 1
minute without stirring, filter with quantitative filter paper. Transfer the filtrate to a 600-mL beaker, wash the
quantitative filter paper with the warm water, combine
the washings and the filterate. Evaporate this solution until to about 300 mL. Place a glass stirring rod in the
beaker, and heat the solution to boiling, add slowly about
10 mL of hydrazine hydrate to the center of beaker by
dropwise addition. Add 2 drops of 10 mol/L sodium hydroxide TS, heat for about 10 minutes to coagulate the
precipitate for ease of filtration, cool, filter with quantita-
tive filter paper. Wash the beaker with warm water, filter
the washing solution, wipe the beaker and stirring rod
with a small piece of quantitative filter paper, place all
the filter papers in the porcelain crucible, cover the crucible heat slowly to carbonize, then ignite at 800 C for 1
hour. Weigh the mass after cooling in the desicator with
silica gel, determine the amount of the residue to the dehydrated carboplatin is between 52.0% and 53.0%.
(4) 1,1-cyclobutanedicarboxylic acidWeigh accurately about 50 mg of Carboplatin, dissolve in mobile
of 1,1-cyclobutanedicarboxylic acid, dissolve in mobile
phase to make exactly 100 mL, add the mobile phase to
2.0 mL of this solution to make 200 mL, and use this solution as the standard solution. Perform the test with 100
L of the test solution and the standard solution as directed under the Liquid Chromatography according to
the following conditions, and measure the peak areas of
1,1-cyclobutanedicarboxylic acid obtained from the test
solution and the standard solution, AT and AS , respectively, by the automatic integration method, calculate the amount of 1,1-cyclobutanedicarboxylic acid: not
more than 0.5%.
Amount (%) of 1,1-cyclobutanedicarboxylic acid
=5
C AT
W AS
C : Concentration (g/mL) of 1,1-cyclobutane dicarboxylic acid in the standard solution.

W : Weight (mg) of Carboplatin taken to prepare the
test solution.
Detector: An ultraviolet absorption photometer (wavelength : 220 nm)
Column: A stainless steel column, about 4.0 mm in inside diameter and about 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography.
Mobile phase: Dissolve 8.5 g of tetrabutylammonium
hydrogen sulfate in 80 mL of water. Add 3.4 mL of
phosphoric acid, and adjust with 10 mol/L sodium hydroxide to a pH of 7.55. Add 20 mL of this solution to a
mixture of 880 mL of water and 100 mL of acetonitrile,
mix.
System suitability
System performance: Mix 1.0 mL of the standard
solution and 1.0 mL of the standard solution in the Assay,
and use this solution as the system suitability solution.
When the procedure is run with 100 L of this solution
under the above operating conditions, the relative retention times of carboplatin peak and 1,1-cyclobutane dicarboxylic acid peak are 0.65 and 1.0, respectively, with
the resolution between carboplatin and 1,1-cyclobutane
dicarboxylic acid peaks being not less than 2.5, and the
column efficiency, determined from the 1,1-cyclobutane
KP 9 161
dicarboxylic acid peak, is not less than 1500 theoretical
plates.
System repeatability: when the test is repeated 6
times with 20 L of system suitability solution under the
above operating conditions, the relative standard deviation of peak area obtained from 1,1-cyclobutane dicarboxylic acid is not more than 10 %.
(5) Related substancesDissolve 50 mg of Carboplatin in water, and use this solution as the test solution.
Separately, dissolve 25 mg of Carboplatin RS in water to
make exactly 100 mL, add water to 1.0 mL of this solution to make exactly 100 mL, and use this solution as the
standard solution. Perform the test with 10 L each of
the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions. The total peak areas other than
carboplatin obtained from the test solution and 1,1cyclobutanedicarboxylic acid by automatic integration
method: is not more than 2 times peak area of carboplatin obtained from standard solution (0.5 %), and each
peak area is not more than the peak area of carboplatin
obtained from the standard solution (0.25 %).
less than 3.0, the numbers of theoretical plates is not less

than 2500, and the symmetry factor of Carboplatin peak
above operating conditions, the relative standard deviation of peak area of carboplatin is not more than 1.2%.
Detector, column, Mobile phase, System suitability
correspond to the the operating conditions in the Assay.
Carisoprodol contains not less than 98.0% and not more

than 102.0% of carisoprodol (C12H24N2O4), calculated on
the dried basis.
Water Not more than 0.5 % (1 g, dehydraed form

amide, volumetric titration, dirct titration).
Description Carisoprodol is a white, crystalline powder,

has slightly specific odor and a bitter taste.
Carisoprodol is freely soluble in acetone, in ethanol or in
chloroform and very slightly soluble in water.
Assay Weigh accurately about 50 mg each of Carboplatin and Carboplatin RS, dissolve in water to make exactly 50 mL, and use these solutions as the test solution
and the standard solution. Perform the test with 10 L
the following operating conditions, measure the peak
areas of Carboplatin and Carboplatin RS, AT and AS ,
by automatic integration method.
Amount (mg) of carboplatin (C6H12N2O4Pt)
= amount (mg) of Carboplatin RS
AT
AS
aminopropylsilanized silica gel for liquid chromatography (between 3 and 10 m in particle diameter).
Mobile phase : A mixture of acetonitrile and water
(87 : 13)
System suitability
with 10 L of the standard solution under the above operating conditions, the ratio of mass distribution is not
Packing and Storage Preserve in light-resistant, tight

containers.
Carisoprodol
CH3
H3C
N
H
NH2
H3C
CH3
C12H24N2O4 : 260.33
Identification (1) Determine the infrared spectra of Carisoprodol and Carisoprodol RS as directed in the potassium bromide disk method under Infrared Spectrophotometry: both spectra exhibit slmilar intensities of absorption at the same wavenumbers.
(2) Weigh 0.1 g each of Carisoprodol and Carisoprodol RS, dissolve in 1.0 mL each of chloroform, and use
these solutions as the test solution and the standard solution. Perform the test with these solutions according to
meprobamate under the Purity: the main spots from the
test solution and the standard solution have the same Rf
value.
Purity (1) Heavy metalsProceed with 2.0 g of Carisoprodol according to Method 2 and perform the test.
(2) Meprobamate Weigh 0.1 g of Carisoprodol and
dissolve in 10 mL of chloroform, use this solution as the
test solution. Separately, weigh 10 mg of Meprobamate
RS, dissolve in 10 mL of chloroform, and use this solution as the standard solution. Spot 10 L and 5 L of the
test solution and the standard solution respectively on the
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform and acetone

Spray evenly, repeatedly by turns, with antimony trichloride TS and 3% solution of furfural in chloroform until
the black spot is developed, heat the plate at 110 for
15 minutes,the spot of meprobamate from test solution is
not more than intense than the spot from standard solution (not more than 0.5%).
Loss on Drying Not more than 0.5% (1 g, vaccum, 60
C, 3 hours).
Assay Weigh acculately about 0.4 g of Carisoprodol,
add 10 mL of pyridine and 1 drop of phenolphthalein TS,
and titrate with 0.1 mol/L sodium methoxide until pink
color is developed. Add 25.0 mL of 0.1 mol/L sodium
methoxide to this solution, heat for 30 minutes with reflux condenser and cool. Add 40 mL of ethanol to this solution, and titrate with 0.1 mol/L hydrochloric acid
VS(Indicator: 7 drops of phenolphthalein TS). Perform
the blank, and make any necessary correction.
1 mL of 0.1 mol/L Sodium Methoxide
= 26.033 mg of C12H24N2O4.
Carmofur
O
C
NHCH2(CH2)4CH3
NH
traviolet-visible Spectrophotometry: both spectra exhibits similar intensities of absorption at the same wavelength.
(3) Determine the infrared spectra of Carmofur and
Carmofur RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
Purity (1) Heavy metalsProceed with 2.0 g of Carmofur according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(2) Related substancesDissolve 0.2 g of Carmofur
in 10 mL of a mixture of methanol and glacial acetic acid
(99 : 1) and use this solution as the test solution. Pipet 1
mL of the test solution, add a mixture of methanol and
glacial acetic acid (99 : 1) to make exactly 500 mL and
plate of silica gel with fluorescent indicator for thin-layer
chromatography. Develop the plate with a mixture of toluene and acetone (5 : 3) to a distance of about 12 cm
than the spot from the standard solution. After exposure
of the plate to bromine vapor for 30 seconds, spray evenly a solution of fluorescein in ethanol (1 in 2500): the

50 C, 3 hours).
C11Hl6FN3O3: 257.26
Carmofur, when dried, contains not less than 98.0% and
not more than 101.0% of carmofur (C11Hl6FN3O3).
Description Carmofur is a white crystalline powder.
Carmofur is very soluble in dimethylformamide, freely
soluble in glacial acetic acid, soluble in ether, sparingly
soluble in methanol or in dehydrated ethanol and practically insoluble in water.
Identification (1) Proceed with 5 mg of Carmofur as
using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid and
prepare the test solution: the test solution responds to the
Qualitative Tests (2) for fluoride.
Carmofur and Carmofur RS in a mixture of methanol and
phosphoric acid - acetic acid - boric acid buffer solution,
(pH 2.0), (9 : 1) (1 in 100000) as directed under the Ul-
Residue on Ignition
Assay Weigh accurately about 0.5 g of Carmofur, previously dried, dissolve in 20 mL of dimethylformamide
and titrate with 0.1 mol/L tetramethylammonium hydroxide-methanol VS until the color of the solution changes
from yellow through blue-green to blue (indicator: 3
drops of thymol blue-dimethylformamide TS).
Each mL of 0.1 mol/L tetramethylammonium hydroxidemethanol VS
= 25.726 mg of C11Hl6FN3O3
KP 9 163
Carteolol Hydrochloride
H
N
O
HCl
H
OCH2CCH2NH
OH
CH3
C
CH3
CH3
and enantiomer
C16H24N2O3HCl: 328.83
Carteolol Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of carteolol hydrochloride (C16H24N2O3HCl).
Description Carteolol Hydrochloride is a white crystal
Carteolol Hydrochloride is soluble in water, sparingly soluble in methanol, very slightly soluble in ethanol or in
glacial acetic acid and practically insoluble in ether.
The solution of Carteolol Hydrochloride (1 in 20) shows
no optical rotation.
pHDissolve 1.0 g of Carteolol Hydrochloride in
100 mL of water: the pH of this solution is between 5.0
and 6.0.
Identification (1) Dissolve 0.1 g of Carteolol Hydrochloride in 5 mL of water and add 5 drops of Reinecke salt TS: a pale red precipitate is produced.
Carteolol Hydrochloride and Carteolol Hydrochloride RS
Spectrophotometry: both sprectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Determine the infrared spectra of Carteolol Hydrochloride and Carteolol Hydrochloride RS as directed
in the potassium cholride disk method under the Infrared
Spectrophotometry: both spectra exhibit similar in tensities of absorption at the same wavenumbers.
(4) A solution of Carteolol Hydrochloride (1 in 50)
g of Carteolol Hydrochloride in 30 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Carteolol
Carteolol Hydrochloride according to Method 3 and perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Carteolol Hydrochloride in 10 mL of methanol and use this solution as the test solution. Pipet 2 mL of the test solution
and add methanol to make exactly 100 mL. Pipet 1 mL

of this solution, add methanol to make exactly 10 mL
the test with the test solution and the standard solution as
L each of the test solution and the standard soution on a
plate of silica gel with a fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
of chloroform, methanol and strong ammonia water (50 :
20 : 1) to a distance of about 12 cm and air-dry the plate.
nm): the spots other than the principal spot from the test
solution are not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately 0.5 g of Carteolol Hydrochloride, previously dried, add 30 mL of glacial acetic acid,
dissolve by heating in a water-bath and cool. After adding 70 mL of acetic anhydride, titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry ). Perform a blank determination and make any necessary correction.
= 32.883 mg of C16H24N2O3HCl
Carvedilol
H
O
OH
H
N
O
OCH3
HN
and enantiomer
C24H26N2O4 : 406.47
Carvedilol, when dried, contains not less than 99.0% and
not more than 101.0% of carvedilol (C24H26N2O4).
Description Carvedilol is a white crystalline powder.
Carvedilol is slightly soluble in ethanol and practically
insoluble in water.
Carvedilol shows polymorphism.
Identification Determine the infrared spectra of Carvedilol and Carvedilol RS, previously dried, as directed

similar intensities of absorption at the same wavenumbers. If any difference appears between the spectra, dissolve Carvedilol and Carvedilol RS in 2-propanol respectively, evaporate to dryness and repeat the test on the residues.
Purity (1) Heavy metalsProceed with 2.0 g of Carvedilol according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(2) Related substances Dissolve 25.0 mg of Carvedilol, accurately weighed, in mobile phase to exactly 10
mL and use this solution as the test solution. Pipet 1.0
mL of the test solution, add mobile phase to make exactly 100 mL, pipet 1.0 mL of this solution, add mobile
standard solution (1). Separately, dissolve 5.0 mg of carvedilol
related
substance
I{(2RS-1-benzyl[2-(2methoxyphenoxy)ethyl]amino-3-(9H-carbazol-4-yloxy)
propan-2-ol)} in 5 mL of the test solution and add mobile phase to make exactly 100 mL and use this solution
as the standard solution (2). To 1.0 mL of standard solution (2) add mobile phase to make exactly 100 mL, pipet
2.0 mL of this solution, add mobile phase to make exactly 10 mL and use this solution as the standard solution
(3). Perform the test with exactly 20 L each of the test
solution and the standard solutions (1) and (2) as directed
under Liquid Chromatography according to the following conditions. Multiply by 2 as correction factor in the
calculation of content of related substance II. The area of
the related substance II obtained in the test solution is not
more than twice that of the principal peak in the chromatogram obtained with standard solution (1) (0.2%), the
area of the related substance I is not more than twice that
of the corresponding peak in the chromatogram obtained
with the standard solution (3) (0.02%), the area of any
other impurity is not more than the area of the principal
peak in the chromatogram from the standard solution (1)
(0.1%), the total area of peaks obtained with the test solution is not more than 5 times that of the principal peak
in the chromatogram from the standard solution (1)
(0.5%). Disregard the peaks that is less than the area of
the principal peak in the chromatogram from the standard solution (3) (0.01%).
inside diameter and about 12.5 cm in length, packed with
octylsilyl silica gel for Liquid Chromatography (5 m in
particle diameter).
about 55 C.
Mobile phase: To 1.77 g of potassium dihydrogen
phosphate add water to make 650 ml, adjust to pH 2.0
with phosphoric acid and add 350 ml of acetonitrile.

the retention time of carvedilol beginning after the solvent peak.
Retention time with reference to the peak of carvedilol (about 4 minutes): 0.6, 3.5, and 6.7 for related substance II, I, and III, respectively.
System suitability
operating condition, the resolution between the peaks of
carvedilol and related substance I is not less than 17.
Loss on Drying Not more than 0.5 % (1 g, 105 C,
constant mass).
Assay Weigh accurately about 0.35 g of Carvedilol,
previous dried, dissolve in 60 mL of glacial acetic acid
= 40.649 mg of C24H26N2O4
Cefaclor Hydrate
HO
O
H2N
Cl
N
H
N
O
H2O
S
H
C15H14ClN3O4SH2O: 385.82
Cefaclor Hydrate contains not less than 860 g (potency)
and not more than 1050 g (potency) per mg of
(C15H14ClN3O4S: 367.81), calculated on the anhydrous
basis.
Description Cefaclor Hydrate is a white to light yellow-white, crystal or crystalline powder, odorless or has
a little of characteristic odor, and has a bit of bitter taste.
Cefaclor Hydrate is soluble in water, sparingly soluble in
methanol, very slightly soluble in ethanol, and practically
insoluble in ether.
Identification (1) Weigh 10 mg of Cefaclor Hydrate,
dissolve in 2 mL of water, add 3 mL of hydroxylamine
hydrochloride TS, allow to stand for 3 minutes, add 1 mL
KP 9 165
of acidic ferric ammonium sulfate TS and shake: a redpurple color develops.
(2) Weigh an appropriate amount of Cefaclor Hydrate
and Cefaclor RS, dissolve each in water to make the solutions contain 4 mg per mL, and use these solutions as
the test solution and the standard solution. Perform the
Chromatography. Spot 10 L of the test solution and the
solvent which is a mixture of acetonitrile, ethylactate,
water and formic acid (30:10:10:1), spray evenly ninhydrin TS: the spots obtained from the test solution and the
standard solution are the same in the Rf value.
(3) Weigh 2 mg of Cefaclor Hydrate, dissolve in water and make to 100 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible
Spectrophotometry, it exhibits maximum between 263
nm and 267 nm.
of Cefaclor Hydrate and Cefaclor RS as directed in the
paste method under Infrared Spectrophotometry, both
same wavenumvers.
(5) Perform the test with Cefaclor Hydrate as directed under Flame Coloration Test: a green color appears.
Purity Related substancesWeigh accurately about
50 mg of Cefaclor Hydrate, dissolve in sodium dihydrogen phosphate TS, pH 2.5 to make exactly 10 mL, and
use this solution as the test solution. Pipet exactly 2 mL
of the test solution, add sodium dihydrogen phosphate
TS, pH 2.5 to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 L each of the test solution and the standard solution as directed under Liquid Chromatography according
to the following conditions, and determine each peak
area. If necessary, proceed with 20 L of sodium dihydrogen phosphate TS, pH 2.5 in the same manner as the
above to compensate the base line to make correction.
The peak areas other than cefaclor from the test solution
are not more than 1/2 of the peak area of cefaclor from
about 25 C.
Mobile phase A: Dissolve 7.8 g pg sodium dihydrogen phosphate in 1000 mL of water, and adjust the pH to
4.0 with phosphoric acid.
Mobile phase B: To 550 mL of the mobile phase A

add 450 mL of acetonitrile for liquid chromatography.
Time (min)
0 ~ 30
30 ~ 45
45 ~ 55
Mobile phase A
(vol %)
95 75
75 0
0
Mobile phase B
(vol %)
5 25
25 100
100

System suitability
mL of the standard solution, and add sodium dihydrogen
phosphate TS, pH 2.5 to make exactly 20 mL. Confirm
that the peak area of cefaclor obtained from 20 L of this
solution is equivalent to 4 to 6 % of that from 20 L of
the symmetry factor of the peak of cefaclor are not less
than 40000 and 0.8 to 1.3, respectively.
peak areas and the retention times of cefaclor are not
more than 2.0 %, respectively.
long as the retention time of cefaclor beginning after the
solvent peak.
D : +105 ~ +120(0.1 g
mm).
Crystalliity Test

of Cefaclor Hydrate in 10 mL of water is between 3.0
and 4.5.
Water Not less than 3.0 and not more than 8.0% (0.2 g,
volumetric titration, direct titration).
Cefaclor Hydrate and Cefaclor Hydrate RS, dissolve
each in a suitable amount of the mobile phase to make
exactly 50 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the
according to the following operating conditions, and obtain the peak areas of cefaclor, AT and AS.
Amount [g (potency)] of cefaclor (C15H14ClN3O4S)
= Amount [g (potency)] of Cefaclor RS
AT
AS

Mobile phase: Weigh 1.0 g of sodium 1pentanesulfonate, dissolve in 750 mL of water, add 10
mL of triethylamine, mix well, and adjust the pH to 2.5
with phosphoric acid. To this solution add 200 mL of methanol.
time of cefaclor is about 4 minutes.
Cefaclor Capsules
Cefaclor Capsules contain not less than 90.0 % and not
more than 120 % of the labeled amount of cefaclor
(C15H14ClN3O4S: 367.81).
Mehtod of Preparation Prepare as directed under
Capsules, with Cefaclor Hydrate.
(1) and (2) under Cefaclor Hydrate.
Disintegration Test It meets the requirement .
Uiformity of Dosage Units It meets the requirement.
direct titration).
twenty Cefaclor Capsules, weigh accurately about 50
mg (potency) of the contents, according to the labeled
potency, dissolve, make exactly 50 mL, and use this solution as the test solution. Perform the test as directed in
the Assay under Cefaclor Hydrate.
Amount [g (potency)] of cefaclor (C15H14ClN3O4S)
= Amount [g (potency)] of Cefaclor RS
AT
AS
Cefadroxil Hydrate
O
HO
CH3
N
H
NH2
H
N
H
H2O
HO
C16H17N3O5SH2O: 381.40
Cefadroxil Hydrate contains not less than 900 g (potency) and not more than 1050 g (potency) per mg of cefadroxil (C16H17N3O5S: 363.39), calculated on the anhydrous basis
Description Cefadroxil Hydrate is a white to light yellow-white powder, has a bit of characteristic odor, but is
tasteless.
Cefadroxil Hydrate is sparingly soluble in water, and
practically insoluble in ethanol or in ether.
the solutions of Cefadroxil Hydrate and Cefadroxil Hydrate RS in ethanol (1 in 50000), as directed under Ultraviolet-visible Spectrophotometry, both spectra exhibit
(2) Determine the infrared spectra of Cefadroxil Hydrate and Cefadroxil Hydrate RS, as directed in the potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
50 mg of Cefadroxil Hydrate, dissolve in a suitable
amount of the mobile phase A, add the mobile phase to
make exactly 50 mL, and use this solution as the test solution. Weigh accurately about 10 mg of D--4Hydroxyphenylglycine RS, dissolve in a suitable amount
of the mobile phase A, add the mobile phase to make exactly 10 mL, and use this solution as the related substance I solution. Weigh accurately about 10 mg of 7aminodesacetoxycephalosporanic acid RS, dissolve in a
suitable amount of phosphate buffer solution, pH 7.0,
add the buffer to make exactly 10 mL, and use this solution as the related substance II solution. Pipet exactly 1
mL each of the related substance I solution and related
substance II solution, add the mobile phase A to make
100.0 mL, and use this solution as the related substance
III solution. Weigh accurately about 10 mg each of dimethylformamide and dimethylacetamide, dissolve in a
suitable amount of the mobile phase A, add the mobile
phase to make exactly 10 mL, pipet exactly 1 mL of this
solution, add the mobile phase A to make exactly 100.0
mL, and use this solution as the related substance IV solution. Pipet exactly one mL of the related substance III
KP 9 167
solution, add the mobile phase A to make exactly 25 mL,
and use this solution as the related substance V solution.
Perform the test with 20 L of each of the test solution,
the related substance III solution, the related substance
IV solution and the related substance V solution as directed under the Liquid Chromatography according to
amount of each of related substances corresponding to
the peak area (Related substance I: not more than 1 %,
other related substances: not more than 3.0 %, total related substances: not more than 3.0 %).
Mobile phase A: Phosphate buffer solution, pH 5.0.
Mobile phase B: Methanol
Time (min)
Mobile phase A
(vol %)
Mobile phase B
(vol %)
0~1
1 ~ 20
20 ~ 23
23 ~ 30
98
98 70
70 98
98
2
2 30
30 2
2
Flow rate: 1.5 mL per minutes.

Relative retention with reference to cefadroxil (retention time is about 6 minutes): dimethylformamide is
about 0.4, and dimethylacetamide is about 0.75.
System performance: When the procedure is run with
the related substance III solution under the above operating conditions, the resolution between the peak of related
substance I and that of related substance II is not less
than 5.0.
D : +164 ~ +182 (0.6 g,
mm).
of Cefadroxil Hydrate in 10 mL of water is between 4.0
and 6.0.
Water Not less than 4.2 % and not more than 6.0%
Assay Weigh accurately about 50 mg of Cefadroxil
Hydrate and Cefadroxil Hydrate RS, dissolve each in a
suitable amount of the water, then add water to make exactly 250 mL. Pipet exactly 10 mL each of these solutions, add water to make exactly 100 mL, and use these
solutions as the test solution and the standard solution.

Perform the test with each of the test solution and the
standard solution as directed under Ultraviolet-visible
Spectrophotometry, and determine absorptions at 264 nm,
AT and AS .
Amount [g (potency)] of cefadroxil (C16H17N3O5S)
= Amount [g (potency)] of Cefadroxil RS
AT
AS

tight containers.
Cefalexin Hydrate
HO
O
CH3
O
H2N
N
H
H
N
O
H2 O
S
H
C16H17N3O4SH2O: 365.40
Cefalexin Hydrate contains not less than 900 g (potency) per mg of cefalexin (C16H17N3O4S: 347.39), calculated on the anhydrous basis.
Description Cefalexin Hydrate is a white to light yellowish white crystals or crystalline powder.
Cefalexin Hydrate is sparingly soluble in water, very
slightly soluble in ethanol, and practically insoluble in
ether.
Identification (1) To 5 mg of Cefalexin Hydrate add 1
mL of hydroxylamine hydrochloride TS, allow to dissolve and stand for 3 minutes, add 1 mL of acidic ferric
ammonium sulfate TS and mix: the red-brown to brown
color develops.
(2) To 20 mg of Cefalexin Hydrate add two to three
drops of 80 % sulfuric acid containing 1 % nitric acid:
the yellow color develops.
(3) To 20 mg of Cefalexin Hydrate add five drops of
1 % glacial acetic acid, two drops of 1 % cupric sulfate
solution and one drop of 2 mol/L sodium hydroxide, and
mix: the yellowish green color develops.
(4) Weigh 3 mg of Cefalexin Hydrate, dissolve in water and add water to make 100 mL. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry, it exhibits maximum
(5) Determine the infrared spectra of Cefalexin Hydrate and Cefalexin RS, as directed in the potassium
at the same wave numbers.
+144 ~ +158
D :
(0.125 g calculated on the anhydrous basis, water, 25 mL,
200 mm).
of Cefalexin Hydrate in 10 mL of water is between 3.0
and 5.5.
Water Not less than 4.0 % and not more than 8.0%
Cefalexin Hydrate and Cefalexin Hydrate RS, dissolve
each in water to make exactly 50 mL. Pipet exactly 5 mL
of each solution, add exactly 5 mL of the internal standard solution and water to make exactly 50 mL, and use
operating conditions, and calculate the ratios, QT and
QS , of the peak area of cefalexin to that of the internal
standard.
Amount [g (potency)] of cefalexin (C16H17N3O4S)
= Amount [g (potency)] of Cefalexin Hydrate RS
Q
T
QS
Internal standard solutionWeigh accurately about

0.1 g of Cephaloglycin RS, dissolve in the mixture of
water and methanol (9:1) to make 100 mL.
Mobile phase: Adjust the pH of 0.05 mol/L potassium dihydrogenphosphate solution to 3.0 with phosphoric acid. To 800 mL of this solution add 200 mL of
methanol and mix.
Cefalotin Sodium
NaO
O
O
O
N
S
H
N
O
S
H
CH3
C16H15N2NaO6S2: 418.42
Cefalotin Sodium contains not less than 850 g (potency) per mg of cefalotin (C16H16N2O6S2: 396.44), calculated on the anhydrous basis.
Description Cefalotin Sodium is a white to light yellowish white crystals or crystalline powder.
Cefalotin Sodium is freely soluble in water, slightly soluble in methanol, very slightly soluble in ethanol, and
Identification (1) To 20 mg of Cefalotin Sodium add
two to three drops of 80 % sulfuric acid containing 1 %
nitric acid: the yellowish green color develops, and the
color turns to red-brown shortly.
(2) Determine the absorption spectra of the 0.0025 %
aqueous solutions of Cefalotin Sodium and Cefalotin Sodium RS from 220 nm to 310 nm as directed under Ultraviolet-visible Spectrophotometry, both spectra exhibit
maximum and minimum at the same wavelengths.
(3) Place 20 mg of Cefalotin Sodium in platinum dish,
ignite, add 5 mL of water and 0.5 mL of hydrochloric acid, dissolve, and filter. The filtrate responds to the Qualitative Tests 1) for sodium salt.
water, 100 mL, 100 mm).
[ ]20
D : +124 ~ +134 (5.0 g,

of Cefalexin Hydrate in 10 mL of water is between 5.0
and 7.5.
Sterility Test It meets the requirement, when Cefalotin
Sodium is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Cefalotin
Sodium is used in a sterile preparation,. Weigh an appropriate amount of Cefalotin Sodium, dissolve in water,
make the solution containing 50 mg (potency) per mL,
and use the solution as the test solution. The amount of
injection is 1.0 mL of the test solution per kg of body
weight of rabbit.
direct titration).
Cefalotin Sodium and Cefalotin Sodium RS, dissolve
each in the mobile phase to make exactly 20 mL, and use
operating conditions, and determine the peak areas, AT
and AS , of cefalotin of these solutions.
KP 9 169
Amount [g (potency)] of cefalotin (C16H16N2O6S2)

= Amount [g (potency)] of Cefalotin Sodium RS
AT
AS
Column: A stainless steel column, about 4.6 mm in inside diameter and about 250 mm in length, packed with
about 40 C.
Mobile phase: Dissolve 17 g of sodium acetate trihydrate in 790 mL of water, and add 0.6 mL of glacial acetic acid. If necessary, adjust the pH to 5.9 with 0.1 mol/L
sodium hydroxide TS or glacial acetic acid. To this solution add 150 mL of acetonitrile and 70 mL of ethanol.
System suitability
System performance: Heat the standard solution in
a water bath of 90 o C for 10 minutes, and cool. Measure
exactly 2.5 mL of this solution, and add the mobile phase
to make exactly 100 mL. When the procedure is run with
10 L of this solution under the above operation conditions, the resolution between peak of cefalotin and the
peak, having the relative retention time of 0.5 with respect to cefalotin is not less than 9, and the symmetry
factor of the peak of cefalotin is not more than 1.8.
above operating conditions, the relative standard deviation of the peak area of cefalotin is not more than 1.0 %.
Cefamandole Nafate
H3C
NaO
N
H
O
H
S
N
H
N
O
C19H17N6NaO6S2: 512.50
Cefamandole Nafate contains not less than 810 g (potency) and not more than 1000 g (potency) per mg of
cefamandole (C18H18N6O5S2: 462.51), calculated on the
anhydrous basis
Description Cefamandole Nafate is a white powder.
Cefamandole Nafate is soluble in water or in ethanol,
and very slightly soluble in ethylacetate, in chloroform,

in ether or in benzene.
Identification Dissolve Cefamandole Nafate in water
to make the solution contain 1 mg per mL, and use this
solution as the test solution. Separately, dissolve Cefamandole Nafate RS in water to make the solution contain
1 mg per mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot the test solution
and the standard solution on a plate of silica gel for thinlayer chromatography. Develop the plate with the developing solvent which is a mixture of n-butanol, glacial
acetic acid and water (4:1:1), and air-dry the plate. Spray
evenly the mixture of starch TS, glacial acetic acid and
0.1 mol/L iodine solution (50:3:1): the white spots on
purple backgrounds, obtained from the test solution and
the standard solution are the same in the Rf value.
Cefamandole Nafate in 10 mL of water is between 3.5
and 7.0.
Sterility Test It meets the requirement, when Cefamandole Nafate is used in a sterile preparation.
Cefamandole Nafate, when it is used in a sterile preparation.
direct titration).
Assay The Standard curve method (1) Culture medium Agar media for seed and base layer- Use the me1 or
2 under Microbial Assay for
dium in I 2 1) (3)
Antibiotics.
(2) Test organism- Staphylococcus aureus ATCC
6538P.
(3) Weigh accurately an appropriate amount of Cefamandole Nafate, dissolve in 0.1 mol/L phosphate buffer solution, pH 8.0 to make the solution so that each mL
contains 1 mg (potency), hydrolyze at 37 C for 60 minutes in water bath, and pipet exactly an appropriate
amount of this solution and dilute in 1 % phosphate buffer solution, pH 6.0 to make solution so that each mL
contains 2.00 g (potency) and use this solution as the
test solution. Separately, weigh accurately an appropriate
amount of Cefamandole Nafate RS, dissolve in 0.1 mol/L
phosphate buffer solution, pH 8.0 to make the solution so
that each mL contains 1 mg (potency), and allow to stand
at 37 C in water bath for 60 minutes. Keep the standard
stock solution at not exceeding 5 C and use within one
day. Pipet exactly an appropriate amount of this solution
and dilute in 1 % phosphate buffer solution, pH 6.0 to
make solutions so that each mL contains 1.28, 1.60, 2.00,
2.50, and 3.12 g (potency), and use these solutions as
the standard solutions. Also use the solution containing

2.00 g (potency) per mL as the standard mid-diluted solution. Perform the test with these solutions according to
the Standard curve method (II 4) as directed under Microbial Assay for Antibiotics.

tight containers.
phosphate buffer solution, pH 6.0 to make exactly 100

mL, and use these solutions as the test solution and the
the following operating conditions, and calculate the ratios, QT and QS , of the peak area of cefapirin to that of
the internal standard.
Amount [g (potency)] of cefapirin (C17H17N3O6S2)
Cefapirin Sodium
= Amount [g (potency)] of Cefapirin Sodium RS

NaO
O
O
QT
QS
O
N
CH3
H
N
S
O
Internal standard solutionA solution of vanillin (1

in 1000)
S
H
C17H16N3NaO6S2: 445.45
Cefapirin Sodium contains not less than 855 g (potency) and not more than 1000g (potency) per mg of cefapirin (C17H17N3O6S2: 423.46), calculated on the anhydrous basis.
Description Cefapirin Sodium is a white to yellowish
white powder.
Cefapirin Sodium and Cefapirin Sodium RS, as directed
spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Cefapirin Sodium responds to the Qualitative
of Cefapirin Sodium in 10 mL of water is between 6.5
and 8.5.
Sterility Test It meets the requirement, when Cefapirin
Pyrogen Test It meets the requirement, when Cefapirin
Sodium is used in a sterile preparation,. Weigh appropriate amount of Cefapirin Sodium, dissolve in water, make
the solution containing 0.1 g (potency) per mL, and use
the solution as the test solution. The amount of injection
is 1.0 mL of the test solution per kg of body weight of
rabbit.
about 40 C.
Mobile phase: Weigh 7.0 g of sodium dihydrogenphosphate dihydrate dissolve in 800 mL of water, adjust
the pH to 2.5 ~2.7 with diluted phosphoric acid (1 in 15),
and add water to make 1000 mL. To 930 mL of this solution add 70 mL of acetonitrile.
time of cefapirin is about 7 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, cefapirin and the internal standard are
above operating conditions, the relative standard deviation of the ratios of the peak area of cefapirin to that of
the internal standard is not more than 1.0 %.
Cefatrizine Propylene Glycol

HO

direct titration).
O
N
H

Cefapirin Sodium and Cefapirin Sodium RS, dissolve
each in 1 % phosphate buffer solution, pH 6.0 to make
exactly 100 mL. Pipet exactly 5 mL of each solution, add
exactly 5 mL of the internal standard solution and 1 %
NH2
H
N
N
H
S
N
HO
H
OH
OH
H3C
NH
KP 9 171
C18H18N6O5S2 (C3H8O2)n
Cefatrizine Propylene Glycol contains not less than 780
g (potency) per mg of cefatrizine (C18H18N6O5S2:
Description Cefatrizine Propylene Glycol is a white to
yellowish white powder, odorless, and has a bit of bitter
taste.
Cefatrizine Propylene Glycol is sparingly soluble in water, and practically insoluble in methanol, in ethanol or in
ether.
Identification (1) To 5 mg of Cefatrizine Propylene
Glycol add 1 mL of hydroxylamine hydrochloride TS, allow to dissolve and stand, add 1 mL of acidic ferric ammonium sulfate TS and mix: the red-brown to brown
color develops.
(2) Dissolve 5 mg of Cefatrizine Propylene Glycol in
5 mL of water, add 1 mL of ammonium chlorideammonia TS, mix, and add 1 mL of 4aminoantipyrin TS and 1 mL of potassium ferric hexacyanate TS: the red color develops.
(3) To 10 mg of Cefatrizine Propylene Glycol add 1
mL of water, allow to dissolve, add 1 mL of potassium
periodate TS, allow to stand for 5 minutes, add 1 mL of
sulfurous acid water, shake, and add 1 mL of fuchsinsulfurous acid TS and allow to stand for 30 minutes:
the red-purple color develops.
of Cefatrizine Propylene Glycol in 10 mL of water is
Absorbance
2000 mL).
Amount [g (potency)] of cefatrzine (C18H18N6O5S2)

= Amount [g (potency)] of Cefatrizine Propylene Glycol RS
AT
AS
Mobile phase: Dissolve 2.04 g of potassium dihydrogenphosphate in water to make 1500 mL, and add 500
mL of methanol.
time of cefatrizine is about 6 minutes.
System suitability
System performance: Weigh accurately about 5 mg
(potency) of Cefadroxil and about 10 mg of Cefatrizine
Propylene Glycol, dissolve in 50 mL of water. When the
procedure is run with 10 L of the solution under the
above operating conditions, cefadroxil and cefatrizine are
above operating conditions, the relative standard deviation of the peak areas of cefatrizine are not more than
1.0 %.
Cefazolin Sodium
%
E11cm
(270 nm): 190 ~ 220 (40 mg, water,
NaO
CH3
S
Purity Heavy metalsProceed with 1.0 g of Cefatrizine Propylene Glycol according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
direct titration).
Cefatrizine Propylene Glycol and Cefatrizine Propylene
Glycol RS, dissolve each in water to make exactly 25 mL,
and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L
the following operating conditions, and calculate the
peak areas, AT and AS , of cefatrizine of these solutions.
O
N
S
N
H
N
N
H
O
N
C14H13N8NaO4S3: 476.49
Cefazolin Sodium contains not less than 860 g (potency) per mg of (C14H14N8O4S3: 454.51), calculated on the
anhydrous basis.
Description Cefazolin Sodium is a white to light yellow-white, crystal or crystalline powder, odorless and
has a bit of bitter taste and salty taste.
Cefazolin Sodium is freely soluble in water, slightly soluble in methanol, and practically insoluble in ethanol or
in ether.
Identification (1) Weigh 10 mg of Cefazolin Sodium,

hydrochloride TS, allow to stand for 5 minutes, add 1 mL
of acidic ferric ammonium sulfate TS and shake: a redbrown color develops.
(2) Weigh 50 mg of Cefazolin Sodium, add 50 mL of
0.1 mol/L hydrochloric acid TS, heat for 10 minutes in
water bath, and cool. Pipet 20 mL of this solution in a
separator, add 20 mL of chloroform, shake well, filter
through fat-free cotton and anhydrous sodium sulfate. To
10 mL of the filtrate add 1 mL of cobalt acetate TS: a
light blue color develops.
(3) Weigh 10 mg of Cefazolin Sodium, dissolve in
water and make to 500 mL. Determine the absorption
spectrum of this solution as directed under Ultravioletvisible Spectrophotometry, it exhibits maxima between
270 nm and 274 nm.
(4) Cefazolin Sodium responds to the Qualitative
[ ] 20
D :
-18 ~ -25(2.5 g,
with octadecylsilanized silica gel for liquid chromatography (10 m in particle diameter)
Mobile phase: Dissolve 2.27 g of disodium hydrogen
phosphate and 0.47 g of citric acid in water to make 935
mL, and add 65 mL acetonitrile.
time of cefazolin is about 8 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, cefazolin and p-acetoanisidide are

tight containers.

Cefazolin Sodium in 10 mL of water is between 4.5 and
6.5.
Cefixime Hydrate
O
Absorbance
100 mL).
%
E11cm
HO
(272 nm): 264 ~ 292 (1.6 mg, water,
Bacterial Endotoxins Less than 0.10 EU per mg of cefazolin, when Cefazolin Sodium is used in a sterile preparation.
direct titration).
Cefazolin Sodium and Cefazolin RS, dissolve each in a
suitable amount of the internal standard solution to make
test with the test solution and the standard solution as directed under the Liquid Chromatography according to
the following operating conditions, and determine the ratios, QT and QS, of the peak area of cefazolin to that of
Amount [g (potency)] of cefazolin (C14H14N8O4S3)
= Amount [g (potency)] of cefazolin RS
Sterility Test It meets the requirement when tested

when Cefazolin Sodium is used in a sterile preparation.
QT
QS
Internal standard solutionWeigh 0.55 g of pacetoanisidide, and dissolve in 1000 mL of 0.1 mol/L
phosphate buffer solution, pH 7.0.
OH
CH2
H
N
S
O
N
3 H2 O
H2N
C16H15N5O7S23H2O: 507.50
Cefixime Hydrate contains not less than 900 g (potency) per mg of cefixime (C16H15N5O7S2: 453.45), calculated on the anhydrous basis.
Description Cefixime Hydrate is a white to light yellowish white crystalline powder, odorless or has a little
bit of a characteristic odor.
Cefixime Hydrate is freely soluble in methanol or in dimethylsulfoxide, sparingly soluble in acetone, slightly
soluble in ethanol, and practically insoluble in water, in
ethylacetate, in ether or in hexane.
Identification (1) Weigh 10 mg of Cefixime Hydrate,
dissolve in 0.5 mL of sodium hydrogen carbonate solution (21 in 2500) and 1.5 mL of water, add 3 mL of hydroxylamine hydrochloride TS, allow to stand for 5 minutes, and 1 mL of acidic ferric ammonium sulfate TS
and mix with shaking: the red-brown color develops.
(2) Weigh 1 mg of Cefixime Hydrate, dissolve in one
drop of sodium hydrogen carbonate solution (21 in 2500)
and 4 mL of water, add 1 mL of dilute hydrochloric acid,
cool down in ice bath and add 1 mL of fresh prepared
sodium nitrite solution (1 in 100), mix with shaking, al-
KP 9 173
low to stand for 2 minutes in ice water, add 1 mL of ammonium sulfamate TS in ice bath with shaking, allow to
stand for one minute, and add 1 mL of N-1naphtylethylenediamine dihydrochloride solution (1 in
1000) and mix with shaking; the red-purple color develops.
of Cefixime Hydrate in 0.1 mol/L phosphate buffer solution, pH 7.0 (1 in 62500) as directed under Ultravioletvisible Spectrophotometry, it exhibits maximum between
286 nm and 290 nm, and minimum between 248 nm and
256 nm.
D : -73 ~ -88(0.45 g
calculated on the anhydrous basis, 50 mL, 100 mm).
pH The pH of a saturated solution of Cefixime Hydrate
in water is between 2.4 and 4.1.
this solution add 110 mL of acetonitrile, degas, and use

the solution.
time of cefixime is about 9 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, cefixime and 2-naphthalenesulfonic acid are eluted in this order with the resolution between
the ratios of the peak area of cefixime to that of the internal standard is not more than 2.0 %.
Cefoperazone Sodium
1%
Absorbance E1 cm (288 nm): 500 ~ 550 (70 mg calculated on the anhydrous basis, 0.1 mol/L phosphate buffer solution, pH 7.0, 5 L).
CH3
Water Not more than 12.0 % (0.1 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.11 mg (potency) each
of Cefixime Hydrate and Cefixime RS, dissolve each in
0.1 mol/L phosphate buffer solution, pH 7.0 to make exactly 100 mL, pipet exactly 10 mL each of these solutions, add 10 mL of the internal standard solution and 0.1
mol/L phosphate buffer solution, pH 7.0 to make exactly
the standard solution, respectively. Perform the test with
5 L each of the test solution and the standard solution as
the following operating conditions, and determine the ratios, QT and QS, of the peak area of cefixime to that of
Amount [g (potency)] of cefixime (C16H15N5O7S2)
= Amount [g (potency)] of Cefixime RS
QT
QS
Internal standard solutionWeigh 0.37 g of 2naphthalenesulfonic acid, dissolve in 100 mL of 0.1

mol/L phosphate buffer solution, pH 7.0.
Mobile phase: To 25 mL of tetrabutylammonium hydroxide TS add water to make 1000 mL, adjust the pH to
6.5 with diluted phosphoric acid (1 in 10). To 290 mL of
NaO
N
N
N
N
HN
O
H
H
N
N
CH3
S
O
HO
C25H26N9NaO8S2: 667.65
Cefoperazone Sodium contains not less than 870 g (potency) and not more than 1015g (potency) per mg of cefoperazone (C25H27N9O8S: 645.67), calculated on the anhydrous basis.
Description Cefoperazone Sodium is a white to yellowish white crystalline powder, odorless, and has a little
of bitter taste.
Cefoperazone Sodium is freely soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol or in ether.
Cefoperazone Sodium and Cefoperazone RS, as directed
spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Weigh an appropriate amount each of Cefoperazone Sodium and Cefoperazone RS, dissolve in the mixture of acetone and water (9:1) to make the solutions so
that each mL contains 1.0 mg, and use these solutions as
and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with the developing solvent which is a mixture of methylethylketone, glacial acetic acid, and water

(18:3:3). Then allow the plate under ultra-violet light
(main wavelength: 254 nm); the spots obtained from the
test solution are the same with the corresponding spots
from the standard solution in the Rf value, respectively.
the same as that of the principal peak in the chromatogram obtained with the standard solution
(4) Cefoperazone Sodium responds to the Qualitative
Crystalliity Test

of Cefoperazone Sodium in 10 mL of water is between
4.5 and 6.5.
Sterility Test It meets the requirement, when Cefoperazone Sodium is used in a sterile preparation.
Bacterial Endotoxins Less than 0.20 EU per mg (potency) of cefoperazone, when Cefoperazone Sodium is
used in a sterile preparation.
velength: 254 nm)

Mobile phase: To 60.1 g of acetic acid and 0.101 g of
triethylamine add water to make exactly 1000 mL. To
1.20 mL of this solution add 2.80 mL of dilute acetic acid
and 120 mL of acetonitrile and water to make exactly
1000 mL.
Flow rate: 1 mL per minute
System suitability
with 25 L of the standard solution under the above operation conditions, the internal standard and cefoperazone are eluted in this order with the resolution between
times with 25 L of the standard solution under the operating conditions, the relative standard deviation of the ratios of the peak area of cefoperazone to that of the internal standard is not more than 1.0 %.
Water Crystalline powder: not more than 5.0 % (0.2 g,

volumetric titration, direct titration). Freeze-dried powder: not more than 2.0 % (0.5 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.1 g (potency) of Cefoperazone Sodium, dissolve in the mobile phase to make
exactly 100 mL, pipet exactly 10 mL of this solution, add
10.0 mL of the internal standard solution and the mobile
test solution. Separately, weigh accurately about 0.1 g
(potency) of Cefoperazone RS, dissolve in 5 mL of 0.1
mol/L phosphate buffer solution, pH 7.0, and add the
mobile phase to make exactly 100 mL. Pipet exactly 10
mL of this solution, add 10.0 mL of the internal standard
solution and the mobile phase to make exactly 50 mL,
the test with 25 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and
determine the ratios, QT and QS, of the peak area of cefoperazone to that of the internal standard.
Amount [g (potency)] of cefoperazone (C25H27N9O8S)
= Amount [g (potency)] of Cefoperazone RS
QT
QS

50 mg of acetanilide, add the mobile phase to make exactly 100 mL.
Detector: An ultraviolet absorption photometer (wa-
Cefotaxime Sodium
NaO
O
O
S
N
N
CH3
H
N
H2N
N
O
O
CH3
S
H
C16H16N5NaO7S2: 477.45
Cefotaxime Sodium contains not less than 914 g (potency) per mg of cefotaxime (C16H17N5O7S2: 455.47),
Description Cefotaxime Sodium is a white to light yellowish white crystalline powder and odorless, or has a bit
of characteristic odor.
Cefotaxime Sodium is freely soluble in water, sparingly
Identification (1) To 2 mg of Cefotaxime Sodium add
0.05 mL of water and 2 mL of sulfuric acidformalde
hyde TS, mix with shaking: the yellow color develops.
When this solution is heated in a boiling water bath for
one minute, the color turns to brown.
(2) Determine the infrared spectra of Cefotaxime Sodium and Cefotaxime Sodium RS, as directed in the potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Weigh about 20 mg each of Cefotaxime Sodium
KP 9 175
and Cefotaxime Sodium RS, dissolve in 5 mL of the
mixture of methanol and 0.067 mol/L phosphate buffer
solution, pH 8.0, and use these solutions as the test solution and the standard solution. Perform the test with
these solutions as directed under Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with the developing solvent which is a mixture of 2
mol/L ammonium acetate solution, pH 6.2 adjusted with
acetic acid, and acetone (85:15). Then allow the plate
spots obtained from the test solution are the same with
the corresponding spots from the standard solution in the
Rf value, respectively.
(4) Place 50 mg of Cefotaxime Sodium in platinum
dish, ignite, add 10 mL of water and 1 mL of hydrochloric acid, dissolve, and filter. The filtrate responds to the
Qualitative Tests 1) for sodium salt.
D : +58 ~ +64 (0.1 g
after being dried, water, 10 mL).
Cefotaxime Sodium in 10 mL of water is between 4.5
and 6.5.
%
E11cm
Absorbance
(235 nm): 360 ~ 390 (20 mg calculated on the dried basis, water, 1000 mL).
Purity (1) Related substancesPerform the test according to the Assay of Cefotaxime Sodium. Weigh accurately about 25 mg of Cefotaxime Sodium, dissolve in
the mobile phase to make exactly 25 mL, pipet exactly 1
mL of this solution and add the mobile phase to make
100 mL, and use this solution as the test solution. Time
span of measurement is about 3 times as long as the retention time of cefotaxime beginning after the solvent
peak (Each peak area other than cefotaxime is not more
than 1.0 % and the total of these peak areas is not more
than 3.0 %).
(2) DimethylanilineWeigh accurately about 1.0 g
of Cefotaxime Sodium, add 5 mL of 1 mol/L sodium hydroxide TS and 1 mL of the internal standard solution, if
necessary, centrifuge, use the supernatant as the test solution. Separately, weigh accurately about 50 mg of dimethylaniline, add 2 mL of hydrochloric acid and water to
make 50 mL. Pipet exactly 1.0 mL, add 5.0 mL of 1
mol/L sodium hydroxide TS and 1.0 mL of the internal
standard solution, if necessary, centrifuge, use the supernatant as the standard solution. Perform the test with the
the Gas Chromatography according to the following
peak area of dimethylaniline to that of the internal standard for the test solution and the standard solution, respectively. (not more than 20 ppm)
Amount (ppm) of dimethylaniline =

amount (mg) of dimethylaniline taken
the content (%) of dimethylaniline
1
QT
amount of CefotaximeSodium taken 50 QS 100000

Internal standard solutionDissolve 50.0 mg of
naphthalene in cyclohexane and make 50 mL. Pipet 5.0
mL of this solution, add cyclohexane to make 100 mL,
and use this solution as the internal standard solution.
Detector: A hydrogen flame ionization detector.
and 2 m in length, packed with diatomaceous earth for
gas chromatography impregnated with 3 % m/m of a
mixuture of polyphenylmethylsiloxane.
Column temperature: 120 o C
Injector and detector temperature: 150 o C
Carrier gas: Nitrogen gas
Sterility Test It meets the requirement, when Cefotaxime Sodium is used in a sterile preparation.
Bacterial Endotoxins Less than 0.05 EU per mg (potency) of cefotaxime, when Cefotaxime Sodium is used
in a sterile preparation.
Loss on Drying Not more than 3.0 % (1 g, 105 C, 3
hours).
Cefotaxime Sodium and Cefotaxime Sodium RS, dissolve each in the mobile phase to make exactly 25 mL,
pipet exactly 2 mL each of these solutions, add the mobile phase to make exactly 200 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the test
Liquid Chromatography according to the following operating conditions, and determine the peak areas, AT and
AS , of cefotaxime of these solutions.
Amount [g (potency)] of cefotaxime (C16H17N5O7S2)

= Amount [g (potency)] of Cefotaxime Sodium RS
AT
AS
Mobile phase: A mixture of phosphate buffer, pH 7.0

and methanol (100:18).
System suitability
System performance: Add 1.0 mL of diluted hydrochloric acid to 4.0 mL of the test solution. Heat the
solution at 40 C for 2 hours. Add 5.0 mL of 0.05 mol/L
phosphate buffer solution, pH 6.6 and 1.0mL of diluted
sodium hydroxide TS and 1 mL of the standard solution.
Use this solution as the reference solution. When the
procedure is run with the reference solution under the
above operation conditions, the resolution between the
two peaks is not less than 3.5.
Cefoxitin Sodium
with the developing solvent which is a mixture of chloroform, acetone, and formic acid (10:9:1) to a distance of
about 10 cm, and air-dry the plate. Spray evenly pdimethylaminocinnamaldehyde TS on the plate and heat
the plate at about 80 C for 5 minutes. The red-purple
spots obtained from the test solution and the standard solutions are the same in the Rf value.
(4) Cefoxitin Sodium responds to the Qualitative
+200 ~ +218
D :
(0.25 g calculated on the anhydrous basis, methanol, 25
mL, 100 mm).
Cefoxitin Sodium in 10 mL of water is between 4.2 and
7.0.
1%
NaO
O
O
O
N
NH2
H
N
O
S
H
CH3
C16H17N3NaO7S2: 449.44
Cefoxitin Sodium contains not less than 860 g (potency) per mg of cefoxitin (C16H17N3O7S2: 427.46), calculated on the anhydrous basis.
Description Cefoxitin Sodium is a white to light yellowish white particle or powder, and has a little bit of a
characteristic odor.
Cefoxitin Sodium is very soluble in water, soluble in methanol, slightly soluble in ethanol, and practically insoluble in ether.
Identification (1) Weigh 50 mg of Cefoxitin Sodium,
hydrochloride TS and 2 mL of 1 mol/L sodium hydroxide TS, allow to stand for 5 minutes, add 3 mL of 1
mol/L hydrochloric acid TS and 1 mL of acidic ferric
ammonium sulfate TS and mix with shaking; the redbrown color develops.
(2) Weigh 25 mg of Cefoxitin Sodium, dissolve in
0.05 mol/L phosphate buffer solution, pH 7.0 and make
1000 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry, it exhibits maxima between 234 nm and 238 nm,
and between 260 nm and 264 nm.
(3) Weigh 20 mg each of Cefoxitin Sodium and Cefoxitin RS, dissolve in methanol to make 10 mL, and use
these solutions as the test solution and the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot 5 L each of the
Absorbance E1 cm (262 nm): 190 ~ 210(2.0 mg calculated on the anhydrous basis, 0.05 mol/L phosphate buffer solution, pH 7.0, 100 mL).
Purity Cefoxitin lactone Weigh accurately about 0.1
g of Cefoxitin Sodium, dissolve in methanol to make exactly 10 mL, and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add methanol to
make exactly 100 mL, and use this solution as the standard solution. Perform the test with the test solution and
the standard solution as directed under Thin-layer Chromatography. Spot 5 L each of the test solution and the
solvent which is a mixture of chloroform, acetone, and
formic acid (10:9:1) to a distance of about 10 cm, and
air-dry the plate. Spray evenly p-dimethylaminocinnam
aldehyde TS on the plate and heat the plate at about 80
C for 5 minutes. The spots other than the principal spot
obtained from the test solution are not more intense than
those obtained from the standard solution (Not more than
1.0 %).
Sterility Test It meets the requirement, when Cefoxitin
Bacterial Endotoxins Less than 0.10 EU per mg of cefoxitin, when Cefoxitin Sodium is used in a sterile preparation.
direct titration).
Assay Weigh accurately about 50 mg (potency) of Cefoxitin Sodium, dissolve in the mobile phase to make exactly 100 mL, and use this solution as the test solution.
Separately, weigh accurately about 10 mg (potency) of
Cefoxitin RS, dissolve in water to make 20 mL, and use
with 10 L each of the test solution and the standard so-
KP 9 177
lution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak areas, AT and AS, of cefoxitin of these
solutions.
Amount [g (potency)] of cefoxitin (C16H17N3O7S2)
= Amount [g (potency)] of Cefoxitin RS
AT
AS
Mobile phase: A mixture of water, methanol and glacial acetic acid (50 : 50 : 1)
time of cefoxitin is about 6 minutes.
Cefradine Hydrate
HO
O
CH3
O
H2N
N
H
H
N
O
2H2O
S
H
C16H19N3O4S2H2O: 385.44
Cefradine Hydrate contains not less than 900 g (potency) and not more than 1050 g (potency) per mg of cefradine (C16H19N3O4S: 349.41), calculated on the anhydrous basis.
Description Cefradine Hydrate is a white to light yellowish white crystalline powder, is odorless or has a little
bit of a characteristic odor and bitter taste.
Cefradine Hydrate is sparingly soluble in water, slightly
Identification (1) Place 50 mg of Cefradine Hydrate in
a stopered test tube, add 2 mL of water and 1 mL of hydrochloric acid, boil for 10 minutes in water bath and
cool: the brown-red color develops.
(2) Determine the infrared spectra of Cefradine Hydrate and Cefradine RS, as directed in the potassium
at the same wavenumbers. If any difference appears between the spectra, dissolve each of Cefradine Hydrate
and Cefradine Hydrate RS in methanol, evaporate to

dryness, and repeat the test on the residues.
of Cefradine Hydrate in 10 mL of water is between 3.5
and 6.0.
Purity (1) Heavy metals Proceed with 2.0 g of Cefradine Hydrate according to Method 2 and perform the
(2) Arsenic Prepare the test solution with 2.0 g of
Cefradine Hydrate according to Method 4 and perform
(3) CefalexinWeigh accurately about 0.1 g of Cefradine Hydrate, dissolve in the mobile phase, make exactly 50 mL, and use this solution as the test solution.
Separately, weigh accurately about 25 mg of Cefalexin
RS, dissolve in the mobile phase, make exactly 250 mL,
the test with exactly 5 L each of the test solution and
determine the peak areas of cefalexin. The peak area of
cefalexin obtained from the test solution is not greater
than that from the standard solution (Not more than
5.0 %).
about 25 C.
Mobile phase: Dissolve 6.8 g of potassium dihydrogen phosphate in 800 mL of water and adjust the pH to
3.0 with dilute phosphoric acid (1 in 10). To 700 mL of
this solution add 100 mL of acetonitrile.
time of cefalexin is about 10 minutes.
System suitability
with 5 L of the test solution under the above operation
conditions, cefalexin and cefradine are eluted in this order with the resolution between these peaks being not
less than 4.0.
times with 5 L of the standard solution under the operating conditions, the relative standard deviation of peak
area of cefalexin is not more than 2.0 %.
Sterility Test It meets the requirement, when Cefradine
Hydrate is used in a sterile preparation.

Bacterial Endotoxins Less than 0.20 EU per mg of cefradine, when Cefradine Hydrate is used in a sterile
preparation.
direct titration).
Cefradine Hydrate and Cefradine RS, dissolve each in
the test stock solution and the standard stock solution.
Pipet exactly 10 mL each of the test stock solution and
the standard stock solution, add the internal standard solution to make exactly 20 mL, and use these solutions as
according to the following operating conditions, and determine the ratios, QT and QS, of the peak area of Cefradine to that of the internal standard.
Amount [g (potency)] of cefradine (C16H19N3O4S)

= Amount [g (potency)] of Cefradine RS
QT
QS
Internal standard solutionWeigh about 0.2 g (potency) of Amoxicillin RS, dissolve in water to make 100
mL.
Mobile phase: The mixture of 0.0052 mol/L sodium
acetate, methanol and glacial acetic acid (800:200:0.12)
System suitability
with 20 L of the standard solution under the above operation conditions, amoxicillin and cefradine are eluted
in this order.
times with 20 L of the standard solution under the operating conditions, the relative standard deviation of the ratios of the peak area of cefradine to that of the internal
standard is not more than 2.0 %.
tight containers.
Ceftazidime Hydrate
O
CH3
HO
CH3
N
H
N
S
O
N
S
H
5H2O
H2N
C22H22N6O7S25H2O: 636.65
Ceftazidime Hydrate contains not less than 950 g (potency) per mg of ceftazidime (C22H22N6O7S2: 546.58),
Description Ceftazidime Hydrate is a white to light
yellowish white powder.
Ceftazidime Hydrate is freely soluble in dimethylsulfoxide or in acetic acid, slightly soluble in water or in methanol, and very slightly soluble in dimethylformamide.
Ceftazidime Hydrate is soluble in 2 mol/L hydrochloric
acid, and in 2 mol/L sodium hydroxide.
Identification Determine the retention times according
to the procedure of Assay: the retention time of the principal peak in the chromatogram obtained with test solution is the same as that of the principal peak in the chromatogram obtained with the standard solution.
Crystalliity Test
quirement.
Ceftazidime Hydrate meets the re-

of Ceftazidime Hydrate in 10 mL of water is between 3.0
and 4.0.
Purity High molecular polymerWeigh accurately
about 0.4 g of Ceftazidime Hydrate, dissolve in the mobile phase, make exactly 100 mL, and use this solution as
the test solution. Use the test solution immediately after
its preparation. Separately, weigh accurately about 4 mg
of Ceftazidime High Moleuclar polymer RS, dissolve in
the mobile phase, make exactly 100 mL, pipet exactly 5
mL of this solution, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution.
Use the standard solution within one hour after its preparation. Perform the test with exactly 100 L each of the
conditions, and determine the peak heights of the high
molecular polymer, HT and HS (Not more than 0.05 %).
Amount (%) of the high molecular polymer
KP 9 179
Amount (mg/mL) of the high molecular
H T polymer in the standard solution

0.1
=
H S Amount (mg/mL) of Ceftazidime Hydrate
hydrophilic gel for gel permeation liquid chromatography
Column temperature: 20 ~ 25 C.
Mobile phase: 0.1 mol/L potassium monohydrogen
phosphate solution
Sterility Test It meets the requirement, when Ceftazidime Hydrate is used in a sterile preparation.
ceftazidime, when Ceftazidime Hydrate is used in a sterile preparation.
Loss on Drying Not less than 13.0 % and not more
than 15.0 % (0.1 g, in vacuum, 60 C, 3 hours).
Ceftriaxone Sodium Hydrate

O
ONa
NaO
CH3
N
N
N
CH3
H
N
O
S
H
3 1/2 H2O
H2N
C18H16N8Na2O7S33H2O: 661.60
Ceftriaxone Sodium Hydrate contains not less than 871
g (potency) per mg of ceftriaxone (C18H18N8O7S3:
Description Ceftriaxone Sodium Hydrate is a white to
light yellowish white crystalline powder.
Ceftriaxone Sodium Hydrate is freely soluble in water or
in propyleneglycol, sparingly soluble in methanol,
slightly soluble in ethanol, and practically insoluble in
chloroform.

Ceftazidime Hydrate and Ceftazidime RS, dissolve each
in phosphate buffer solution, pH 7.0, to make exactly
according to the following operating conditions, and determine the peak area of ceftazidime, AT and AS. Prepare
the test solution and the standard solution under light resistant conditions.

Ceftriaxone Sodium Hydrate and Ceftriaxone Sodium
RS, as directed in the potassium bromide disk method
under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Ceftriaxone Sodium Hydrate responds to the Qualitative Tests 1) for sodium salt.
Amount [g (potency)] of ceftazidime (C22H22N6O7S2)
Sterility Test It meets the requirement, when Ceftriaxone Sodium Hydrate is used in a sterile preparation.
= Amount [g (potency)] of Ceftazidime RS
AT
AS
Column: A stainless steel column packed with octadecylsilanized silica gel for liquid chromatography (3 ~ 10
m in particle diameter)
Mobile phase: To 40 mL of acetonitrile and 200 mL of
phosphate buffer solution, pH 7.0 add water to make 200
mL.
tight containers (Nitrogen-filled, 0 ~ 5 C).

of Ceftriaxone Sodium Hydrate in 10 mL of water is between 6.0 and 8.0.

ceftriaxone, when Ceftriaxone Sodium Hydrate is used in
a sterile preparation.
Assay Weigh accurately about 4.5 mg (potency) each
of Ceftriaxone Sodium Hydrate and Ceftriaxone Sodium
RS, dissolve each in the mobile phase to make exactly
under the Liquid Chromatography according to the following operating conditions, and determine the peak area
of ceftazidime, AT and AS.
Amount [g (potency)] of ceftriaxone (C18H18N8O7S3)

= Amount [g (potency)] of Ceftriaxone Sodium RS
AT
AS
Column temperature: A room temperature
Mobile phase: Weigh 2g of tetra-n-heptylammonium
bromide and 2g of tetra-n-decylammonium bromide, dissolve in 620 mL of acetonitrile, and add 320 mL of water,
55 mL of phosphate buffer solution, pH 7.0, and 5.0 mL
of citric acid buffer solution, pH 5.0.
Cefuroxime Axetil
O
O
N
NH2
N
H
N
S
O
C20H22N4O10S: 510.47
Cefuroxime Axetil contains not less than 745 g (potency) and not more than 875 g (potency) per mg of cefuroxime (C16H16N4O8S: 424.39), calculated on the anhydrous basis.
Description Cefuroxime Axetil is a white to dark yellow powder.
Cefuroxime Axetil is soluble in dimethylsulfoxide, in
dimethylformamide, in 1,4-dioxane, in chloroform, in
methanol, in acetone, in glacial acetic acid or in ethylacetate, and slightly soluble in ethanol, in ether or in toluene.
Cefuroxime Axetil dissolves in 2 mol/L sodium hydroxide TS.
Identification Determine the infrared spectra of Cefuroxime Axetil and Cefuroxime Axetil RS, as directed in
the paste method under the Infrared spectrophotometry:
Isomer Ratio Perform the test according to Assay, and

calculate the content ratio of isomer A by using the following equation (Not less than 0.48 and not more than
0.55).
Amount of isomer A in Cefuroxime Axetil

=
The peak area of isomer A

the peak area of isomer A + the peak area of isomer B
Assay Weigh accurately about 30 mg (potency) of Cefuroxime Axetil and Cefuroxime Axetil RS, dissolve
each in methanol and add methanol to make exactly 25
mL. Pipet exactly 10 mL of each solution, add exactly
5.0 mL of the interal standard solution and 3.8 mL of methanol, mix, add 0.2 mol/L ammonium dihydrogen phosphate solution to make exactly 50 mL, and use these solutions as the test solution and the standard solution. Use
these solutions within 8 hours. Perform the test with 10
the following operating conditions, and determine the ratios, HT and HS, of the peak height of cefuroxime axetil
to that of the internal standard.
Amount [g (potency)] of cefuroxime (C16H16N4O8S)

= Amount [g (potency)] of Cefuroxime Axetil RS
O
O
CH3
O
O
CH3
H3C

direct titration).
HT
HS
HT = (the peak height of isomer A + the peak height

of isomer B, in the test solution)/(the peak height of the
internal standard)
HS = (the peak height of isomer A + the peak height
of isomer B, in the standard solution)/(the peak height of
the internal standard)
54 mg of acetanilide, add methanol to make 10 mL.
methylsilanized silica gel for liquid chromatography (3 ~
10 m in particle diameter)
Mobile phase: To 620 mL of 0.2 mol/L ammonium
dihydrogen phosphate add methanol to make exactly
1000 mL.
System suitability
with the standard solution under the above operation
conditions, the internal standard, cefuroxime axetil isomer B and cefuroxime axetil isomer A are eluted in this
KP 9 181
order with the resolution between isomer A and isomer B

being not less than 1.5. Theoretical plates of the peak of
isomer A is not less than 3000 and the symmetry factor
of the peak of isomer A is not more than 1.5.
times with 5 L of the standard solution under the operating conditions, the relative standard deviation of every
peak is not more than 2.0 %.
Relative retention time: The relative retention time of
isomer B to the internal standard is about 2 and that of
isomer A is about 2.25.
Cefuroxime Sodium
NaO
O
O
O
O
O
CH3
NH2
N
H
N
S
O
C16H15N4NaO8S: 446.37
Cefuroxime Sodium contains not less than 856 g (potency) per mg of cefuroxime (C16H16N4O8S: 424.39),
Description Cefuroxime Sodium is a white to light
yellowish white crystal or crystalline powder, is odorless,
or has a little bit of a characteristic odor.
Cefuroxime Sodium is freely soluble in water, sparingly
Sterility Test It meets the requirement, when Cefuroxime Sodium is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Cefuroxime Sodium is used in a sterile preparation,. Weigh an
appropriate amount of Cefuroxime Sodium, dissolve in
water, make the solution so that each mL contains 50 mg
(potency), and use the solution as the test solution. The
direct titration).
Cefuroxime Sodium and Cefuroxime Sodium RS, dissolve in water to make exactly 100 mL. Pipet exactly 2
mL of each of these solutions, add water to make exactly
each of the test solution and the standard solution as directed under Ultraviolet-visible Spectrophotometry, and
determine the absorbance at absorption maximum around
273 nm, AT and AS, of these solutions.
Amount [g (potency)] of cefuroxime (C16H16N4O8S)

= Amount [g (potency)] of Cefuroxime Sodium RS
AT
AS
Cetirizine Dihydrochloride
Cl

Cefuroxime Sodium and Cefuroxime Sodium RS as directed in the paste method under Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumvers.
(2) Determine the absorption spectra of the 0.0015 %
aqueous solutions each of Cefuroxime Sodium and Cefuroxime Sodium RS from 190 nm to 450 nm as directed
under Ultraviolet-visible Spectrophotometry: both spectra exhibit maximum and minimum at the same wavelengths.
(3) Cefuroxime Sodium responds to the Qualitative
D : +59 ~ +266(0.5 g
mm).
Cefuroxime Sodium in 10 mL of water is between 6.0
and 8.5.
COOH
N
N
H
2HCl
and enantiomer
C21H25ClN2O32HCl : 461.81
Cetirizine Dihydrochloride contains not less than 99.0%
and not more than 100.5% of cetirizine dihydrochloride
(C21H25ClN2O32HCl), calculated on an anhydrous basis.
Description Cetirizine Dihydrochloride is a white
powder.
Cetirizine Dihydrochloride is freely soluble in water, and
practically insoluble in acetone or in methylene chloride.
Identification (1) Dissolve 20.0 mg of Cetirizine Di-
hydrochloride in 0.1 mol/L hydrochloric acid to make

100 mL. Dilute 10.0 mL of this solution with 0.1 mol/L
hydrochloric acid to 100 mL. Determine the absorption
spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry. Absorption maximum occurs at 231 nm, and the specific absorbance at this wavelength ranges from 359 to 381.
(2) Determine the infrared absorption spectra of Cetirizine Dihydrochloride and Cetirizine Dihydrochloride
(3) Dissolve 10 mg of Cetirizine Dihydrochloride in
water to make 5 mL, and use this solution as the test solution. Separately, dissolve 10 mg of Cetirizine Dihydrochloride RS in water to make 5 mL, and use this solution as the standard solution (1). Separately, dissolve 10
mg of chlorphenamine maleate RS in water to make 5
mL. To 1 mL of the solution, add 1 mL of the standard
solution (1). Use this solution as the standard solution (2).
Perform the test with these solutions as directed under
test solution and the standard solutions (1) and (2) on a
chromatography, develop with a mixture of methylene
chloride, methanol, and ammonia (90 : 10 : 1) to a distance of about 15 cm, and dry the plate in cool air. Examine in ultraviolet light at 254 nm, and compare the
principal spot from the test solution with that from the
standard solution (1). Their Rf values are the same. The
test is valid when 2 clearly separated spots are observed
with the standard solution (2).
(4) The solution of Cetirizine Dihydrochloride in water (1 in 100) responds to the Qualitative Tests for chloride (2nd method).
of Cetirizine Dihydrochloride in 20 mL of water is between 1.2 and 1.8.
Purity (1) Clarity and color of solutionWhen 2.0 g
of Cetirizine Dihydrochloride is dissolved in 20 mL of
water, the resultant solution is clear.
(2) Heavy metals Proceed the test with 2.0 g of
Cetirizine Dihydrochloride according to Method 1. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(3) Related substancesDissolve 20.0 mg of Cetirizine Dihydrochloride in the mobile phase to make 100
dissolve 5.0 mg of Cetirizine Dihydrochloride RS and
5.0 mg of cetirizine related substance I RS {(RS)-1-[(4chlorophenyl)phenylmethyl] piperazine} in the mobile
phase to make 25 mL. Dilute 1.0 mL of the solution to
100 mL with the mobile phase, and use this solution as
the standard solution (1). Dilute 2.0 mL of the test solution to 50 mL with the mobile phase. Dilute 5.0 mL of
this solution to 100 mL with the mobile phase, and use

with 20 L each of the test solution, the standard solutions (1), and (2) as directed under the Liquid Chromatography according to the following conditions. Determine
the area of each peak by the automatic integration method. The peak area of any related substance, excluding
the principal peak area corresponding to cetirizine, from
the test solution is not more that the area of the principal
peak from the standard solution (2) (0.2%); and the sum
of the peak areas of all related substances from the test
solution is not more than 1.5 times the area of the principal peak from the standard solution (2) (0.3%). Disregard any peak areas that are not more than 0.1 times the
principal peak area from the standard solution (2).
Mobile phase: A mixture of acetonitrile, water, and
dilute sulfuric acid (93 : 6.6 : 0.4).
System suitability
system so that the peak heights of cetirizine and the related substance I are about 50% of the full scale of the
recorder. When the procedure is run with 20 L of the
standard solution (1) under the above operation conditions, the resolution between the peaks of cetirizine and
the related substance I is not less 3, and the symmetry
factor is not more than 2.0.
Loss on Drying Not more than 0.5% (1 g, 105 C, constant weight).
Residue on Ignitio Not more than 0.2% (1 g).
Assay Dissolve 0.100 g of Cetirizine Dihydrochloride
in 70 mL of a mixture of water and acetone (30 : 70), titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
correction.

= 15.394 mg of C21H25ClN2O32HCl
Cetraxate Hydrochloride
KP 9 183
O
H2NH2C
H
CH2CH2CO 2H
HCl
C17H23NO4HCl: 341.83
Cetraxate Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of cetraxate hydrochloride (C17H23NO4HCl).
Description Cetraxate Hydrochloride is a white crystal
Cetraxate Hydrochloride is soluble in methanol, sparingly soluble in water or in ethanol and practically insoluble
in ether.
the solutions of Cetraxate Hydrochloride and Cetraxate
Hydrochloride RS in methanol (1 in 2500) as directed
same wavelengths.
(2) Dissolve 0.5 g of Cetraxate Hydrochloride in 5
mL of a mixture of water and 2-propanol (1 : 1) by
warming, cool to below 25 oC. Filter, dry the formed
crystals in vacuum for 4 hours, and further dry at 105 oC
for 1 hour. Determine the infrared spectra of the dried
matter and Cetraxate Hydrochloride RS, previously dried,
the Infrared Spectrophotometry both spectra exhibit
(3) A solution of Cetraxate Hydrochloride (1 in 100)
responds to the Qualitative Tests (2) for chloride.
Purity (1) Heavy metalsProceed with 2.0 g of Cetraxate Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
Cetraxate Hydrochloride according to Method 3 and perform the test with a solution of magnesium nitrate in
(3) Cis isomerDissolve 0.10 g of Cetraxate Hydrochloride in 10 mL of water and use this solution as
the test solution. To exactly 5 mL of the test solution, add
water to make exactly 100 mL. To exactly 2 mL of this
the test solution and the standard solution by the automatic integration method: the area of the peak which has
a retention time 1.3 to 1.6 times that of cetraxate from
the test solution is not larger than the peak area of cetraxate from the standard solution.
about 25 C.
Mobile phase: Adjust the pH of a mixture of water,
methanol and 0.5 mol/L ammonium acetate TS (15 : 10 :
4) to 6.0 with acetic acid.
time of cetraxate is about 10 minutes.
System suitability
System performance: Dissolve 20 mg of Cetraxate
Hydrochloride and 10 mg of phenol in 100 mL of water.
To 2 mL of this solution, add water to make 20 mL.
under the above operating conditions, cetraxate and phenol are eluted in this order with the resolution between
Detection sensitivity: Adjust the detection sensitivity so that the peak height of cetraxate obtained from 10
L of the standard solution is not less than 20 mm.
(4) 3-(p-Hydroxyphenyl)propionic acidTo about

0.10 g of Cetraxate Hydrochloride, add exactly 2 mL of
the internal standard solution and methanol to make 10
dissolve 25 mg of 3-(p-hydroxyphenyl)propionic acid in
methanol to make exactly 100 mL. To exactly 2 mL of
this solution, add exactly 2 mL of the internal standard
solution and methanol to make 10 mL and use this solution as the standard solution. Perform the test with 10 L
the following conditions and calculate the ratio, QT
and QS , of the peak area of 3-(p-hydroxyphenyl) propionic acid to that of the internal standard: QT is not
larger than QS .
Internal standard solutionA solution of Caffeine in
methanol (1 in 4000).
about 40 C
Mobile phase: Adjust the pH of a mixture of water,
methanol and 0.5 mol/L ammonium acetate TS (15 : 5 :
2) to 5.5 with acetic acid.

time of 3-(p-hydroxyphenyl)propionic acid is about 7
minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, 3-(p-hydroxy phenyl) propionic acid
and the internal standard are eluted in this order with the
Detection sensitivity: Adjust the detection sensitivity so that the peak height of 3-(p-hydroxyphenyl) propionic acid obtained from 10 L of the standard solution
is not less than 30 mm.
(5) Related substancesDissolve 0.10 g of Cetraxate Hydrochloride in 10 mL of methanol and use this solution as the test solution. Pipet 1 mL of the test solution,
with a mixture of chloroform, methanol and glacial acetic acid (20 : 4 : 3) to a distance of about 10 cm and airdry the plate. Spray evenly ninhydrin TS on the plate and
heat at 90 C for 10 minutes: the spots other than the
hours).
Chloral Hydrate contains not less than 99.5% and not

more than 101.0% of chloral hydrate (C2H3Cl3O2).
Description Chloral Hydrate is a colorless crystal, has
a pungent odor and an acrid, slightly bitter taste.
Chloral Hydrate is very soluble in water and freely soluble in ethanol or in ether.
Chloral Hydrate slowly volatilizes in air.
Identification (1) Dissolve 0.2 g of Chloral Hydrate in
2 mL of water and add 2 mL of sodium hydroxide TS:
the turbidity is produced and it separates into two clear
layers by warming.
(2) Heat 0.2 g of Chloral Hydrate with 3 drops of aniline and 3 drops of sodium hydroxide TS: the disagreeable odor of phenylisocyanide (poisonous) is perceptible.
g of Chloral Hydrate in 2 mL of water: the solution is
(2) AcidDissolve 0.20 g of Chloral Hydrate in 2
mL of water and add 1 drop of methyl orange TS: a yellow color is observed.
(3) ChloridePerform the test with 1.0 g of Chloral
Hydrate. Prepare the control solution with 0.30 mL of
(4) Chloral alcoholateWarm 1.0 g of Chloral Hydrate with 10 mL of sodium hydroxide TS, filter the upper layer, add iodine TS to the filtrate until a yellow color is observed and allow the solution to stand for 1 hour:
no yellow precipitate is produced.
(5) BenzeneWarm the solution obtained in (1) with
3 mL of water: no odor of benzene is perceptible.
Assay Weigh accurately 0.5 g of Cetraxate Hydrochloride, previously dried, dissolve in 100 mL of water and
adjust the pH of this solution to between 7.0 and 7.5 with
dilute sodium hydroxide TS. To this solution, add 10 mL
of formalin, stir for about 5 minutes and titrate with 0.1
mol/L sodium hydroxide VS for over about 20 minutes
Assay Weigh accurately about 4 g of Chloral Hydrate

in a glass-stoppered flask, add 10 mL of water and 40
mL of 1 mol/L sodium hydroxide VS and allow the mixture to stand for exactly 2 minutes. Titrate the excess sodium hydroxide immediately with 0.5 mol/L sulfuric acid
VS (indicator: 2 drops of phenolphthalein TS). Perform a


= 165.40 mg of C2H3Cl3O2.
Chlorambucil
Chloral Hydrate
Cl
OH
Cl3C
N
OH
O
HO
C2H3Cl3O2: 165.40
Cl
KP 9 185
C14H19Cl2NO2: 304.21
Chlorambucil contains not less than 98.0% and not more
than 101.0% of chlorambucil (C14H19Cl2NO2), calculated
Description Chlorambucil is a milk-white granuleshaped powder.
Chlorambucil is practically insoluble in water and soluble in acetone.
Chlorambucil dissolves in dilute sodium hydroxide TS.
Identification (1) Dissolve 50 mg of Chlorambucil in
5 mL of acetone and dilute with water to make 10 mL.
Add 1 drop of 1 mol/L sulfuric acid and, then, add 4
drops of silver nitrate TS: no opalescence is observed
immediately. Warm this solution on a steam-bath: opalescence develops.
(2) Determine the infrared absorption spectra of solutions of Chlorambucil and Chlorambucil RS in carbon
disulfide (1 to 125) as directed under the Infrared Spectrophotometry, using solid cell with 1 mm of thickness:
Melting Point

direct titration ).
Assay Weigh accurately 0.2 g of Chlorambucil, dissolve in 10 mL of acetone and dilute with 10 mL of water.
Titrate with 0.1 mol/L sodium hydroxide (indicator: 2
drops of phenolphthalein TS).
Each mL of 0.1 mol/L sodium hydroxide

= 30.421 mg of C14H19Cl2NO2
Chlorambucil Tablets
Chlorambucil Tablets contain not less than 85.0% and
not more than 110.0% of the labeled amount of the chlorambucil (C14H19Cl2NO2: 304.22).
Preparation Prepare as directed under Tablets, with
Chlorambucil.
Identification Weigh a portion of powered Chlorambucil Tablets, equivalent to 16 mg of Chlorambucil, add
20 mL of carbon disulfide and shake to mix. Filter and
evaporate the filtrate to dryness. Dissolve the residue in 2
mL of carbon disulfide. Proceed the test with the solution
as directed in the Identification (1) under Chlorambucil.
Disintegration Test Place 1 tablet in each of six tubes

of baskets. If the tablet has a soluble external coating,
immerse the basket in water at room temperature for 5
minutes. Operate the apparatus, using the first solution
maintained at 37 2 C as the immersion fluid. After 30
minutes of operation in the first solution, lift the basket
from the fluid, and observe the tablets. If the tablets have
not disintegrated completely, substitute the second solution maintained at 37 2 C as the immersion fluid, and
continue the test for total period time, including previous
exposure to water and the first solution, equal to 45 minutes. If one or two tablets do not disintegrate, proceed
the test with additional 12 tablets and determine: tablets
which do not disintegrate are not more than 2 out of total
18 tablets.
Chlorambucil Tablets. Weigh accurately a portion of the
powder, equivalent to about 2 mg of chlorambucil
(C14H19Cl2NO2), add 50 mL of ethanol, shake cautiously,
add 5.0 mL of 0.1 mol/L hydrochloric acid and 2.0 mL of
internal standard solution, shake by mechanical means
for 5 minutes and dilute with ethanol to make exactly
100 mL. Filter and use this filtrate as the test solution.
Separately, weigh accurately about 20 mg of Chlorambucil RS, previously dried in a desiccators (silica gel) for
24 hours and dissolve in ethanol to make exactly 20 mL.
To 2.0 mL of this solution, add 50 mL of ethanol, 5.0 mL
of 0.1 mol/L hydrochloric acid and 2.0 mL of internal
standard solution with cautious shaking and dilute with
ethanol to make exactly 100 mL. Use this solution as the
the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine the relative peak
areas compared to internal standard, QT and QS , of
Chlorambucil of the test solution and the standard solution, respectively.
Amounts (mg) of chlorambucil (C14H19Cl2NO2)

= amount (mg) of Chlorambucil RS
QT
1
Q S 10
Internal standard solutionAn ethanol solution (1

in 2500) of propyl p-oxybenzoate.
Operating Conditions
Column: A stainless steel column, about 2 mm in inside diameter and about 25 to 30 cm in length, packed
with octadecylsilanized silica gel for liquid chromatography (5 to 10 m in particle diameter).
Mobile phase: Mix 500 mL of ethanol and 1.0 mL of
glacial acetic acid and add water to make 1000 mL.

System suitability
with 10 L of the standard solution under the above operating conditions, the resolution between peaks of Chlorambucil and internal substance is not less than 2.0.
times with the standard solution, the relative standard
deviation of the peak area of Chlorambucil is not more
than 2.0%.
Packaging and Storage Preserve in well-closed containers (light-resistant, well-closed containers in case of
uncoated tablets).
Chloramphenicol
NO2
OH
O
Cl
N
H
Cl
OH
C11H12Cl2N2O5: 323.13
Chloramphenicol contains not less than 900 g (potency)
of per mg of chloramphenicol (C11H12Cl2N2O5), calculated on the dried basis.
Description Chloramphenicol is a whtie to yellowish
white crystals or crystalline powder, is odorless, and has
a bitter taste.
Chloramphenicol is freely soluble in methanol or in
ethanol, slightly soluble in water or in ether.
Identification (1) Weigh 10 mg of Chloramphenicol,
dissolve in 1 mL of 50 % ethanol, add 3 mL of calcium
chloride solution (1 in 100) and 50 mg of zinc powder,
and heat for 10 minutes in water bath. Decant the supernatant into a test tube, add 0.1 g of glacial acetic acid and
2 drops of benzoyl chloride, mix with shaking for 1
minute, add 10 drops of ferric chloride TS (if the solution
is not clear, add dilute hydrochloric acid): a purple to
red-purple color develops. If the test is run as above except the addition of zinc powder, the solution is colorless.
(2) To 50 mg of Chloramphenicol, add 3 mL of sodium hydroxide ethanol TS, and heat for 15 minutes in
water bath and cool down: The solution responds to the
Qualitative Tests for chloride.
D : +18.5 ~ +21.5
(1.25 g, ethanol anhydrous, 25 mL (dissolve with heating), 200 mm).
Melting Point
pH
Between 149 C and 153 C .
The pH of a saturated solution of Chloramphenicol
in water is between 4.5 and 7.5.

Absorbance
1000 mL).
%
E11cm
(278 nm): 289 ~ 307 (20 mg, water,
Purity (1) Heavy metalsProceed with 2.0 g of Chloramphenicol according to Method 2 and perform the test.
(2) Free chlorineTo 5 mL of 0.1 % aqueous solution of Chloramphenicol, add 2 to 3 drops of silver nitrate TS: no precipitate appears.
Sterility Test It meets the requirement, when Chloramphenicol is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Chloramphenicol is used in a sterile preparation,. Weigh an
appropriate amount of Chloramphenicol, dissolve in saline injection solution to make the solution so that each
mL contains 5.0 mg, and use the solution as the test solution. The amount of injection is 1.0 mL of the test solution per kg of body weight of rabbit.
Loss on Drying Not more than 0.5 % (1.0 g, 100 C).
Chloramphenicol and Chloramphenicol RS, dissolve in
the mobile phase to make exactly 50 mL, and use these
respectively. Perform the test with 10 L of each of the
operating conditions, and determine the peak areas of
chloramphenicol, AT , AS.
Amount [g (potency)] of chloramphenicol

(C11H12Cl2N2O5)
= Amount [g (potency)] of Chloramphenicol RS
AT
AS
Mobile phase: A mixture of water, methanol and
acetic acid (550:450:1)
System suitability
with 10 L of the standard solution under the above operating conditions, the theoretical plate number is not
less than 1800, and the symmetry factor is not more than
KP 9 187
2.0.
above operating conditions, the relative standard deviation of the principal peak area is not more than 1.0 %.
Packaging and Storage Preserve in tight containers .
Chloramphenicol Palmitate
O

(C11H12Cl2N2O5)
= Amount [g (potency)] Chloramphenicol RS
Chloramphenicol Sodium
Succinate
O
H
O
O
O
CI
O2N
N
H
H
OH
CI
C27H42Cl2N2O6: 561.54
Chloramphenicol Palmitate contains not less than 555 g
(potency) and not more than 595 g (potency) of per mg
of chloramphenicol (C11H12Cl2N2O5: 323.13).
Description Chloramphenicol Palmitate is a whtie to
grayish white crystalline powder or powder, and has not
a taste.
Chloramphenicol Palmitate is freely soluble in acetone or
in chloroform, soluble in methanol or in ethanol, and
Identification (1) Determine the absorption spectrum
of 0.0025 w/v % solution of Chloramphenicol Palmitate
in ethanol anhydrous as directed under Ultravioletvisible Spectrophotometry, it exhibits maximum between
268 nm and 274 nm.
(2) Weigh 50 mg of Chloramphenicol Palmitate, add
2 mL of potassium hydroxide ethanol TS, heat for 15
minutes in water bath, and cool down: the solution responds to the Qualitative Tests for chloride.
D : +21 ~ +25 (1.25 g,
ethanol anhydrous, 25 mL (dissolve with heating), 200
mm).
Melting Point
Assay Weigh accurately about 90 mg of Chloramphenicol Palmitate and about 50 mg (potency) of Chloramphenicol RS, dissolve each in ethanol anhydrous to
make exactly 100 mL, pipet exactly 5 mL each of these
solutions, add ethanol anhydrous to make exactly 250
standard solution, respectively. Determine the absorbances, AT and AS, at 271 nm of the test solution and the
standard solution as directed under Ultraviolet-visible
Spectrophotometry.
AT
AS
Cl
R3
NO2
H
N
H
Cl
R1
1 Isomer: R1 = CO-CH2-CH2-CO2Na, R3 = H
3 Isomer: R1 = H, R3 = CO-CH2-CH2-CO2Na
C15H15Cl2N2NaO8: 445.18
Chloramphenicol Sodium Succinate contains not less
than 650 g (potency) of per mg of chloramphenicol
(C11H12Cl2N2O5: 323.13).
Description Chloramphenicol Sodium Succinate is a
whtie to yellow-brown crystalline powder or powder.
Chloramphenicol Sodium Succinate is freely soluble in
water or in methanol.
Identification (1) To 50 mg of Chloramphenicol Sodium Succinate, add 5 mL of pyridine, 5 mL of 1 mol/L
sodium hydroxide TS, mix with shaking, and heat in water bath for several minutes: The pyridine layer turns to
deep red color.
(2) To 0.1 g mg of Chloramphenicol Sodium Succinate, add 0.2 g of resorcin and 0.2 mL of sulfuric acid,
and heat until the color turns to deep red. To this solution,
add water slowly: an orage color with green fluorescence
develops.
(3) Determine the absorption spectrum of 0.002
w/v % aqueous solution of Chloramphenicol Sodium
Succinate as directed under Ultraviolet-visible Spectrophotometry, it exhibits maximum between 271 nm and
281 nm.
(4) Weigh 50 mg of Chloramphenicol Sodium Succinate, add 2 mL of potassium hydroxide ethanol TS, heat
for 15 minutes in water bath, and cool down: the solution
(5) Chloramphenicol Sodium Succinate responds to
the Qualitative Tests 1) for sodium salt.
[ ] 20
D :
+5 ~ +8 (1.25 g,

of Chloramphenicol Sodium Succinate in 10 mL of water
Sterility Test It meets the requirement, when Chloramphenicol Sodium Succinate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Chloramphenicol Sodium Succinate is used in a sterile preparation. Weigh an appropriate amount of Chloramphenicol
Sodium Succinate, dissolve in Isotonic Sodium Chloride
Injection to make a solution so that each mL contains 5.0
mg, and use the solution as the test solution. The amount
of injection is 1.0 mL of the test solution per kg of body
weight of rabbit.
direct titration).
Assay Weigh accurately an amount of Chloramphenicol Sodium Succinate and Chloramphenicol Sodium
Succinate RS, dissolve each in water to make solutions
so that each mL contains 30 g (potency), and use these
respectively. Determine the absorbances, AT and AS, at
276 nm of the test solution and the standard solution as
directed under Ultraviolet-visible Spectrophotometry.

(C11H12Cl2N2O5)
= Amount [g (potency)] Chloramphenicol Sodium Succinate RS
AT
AS
Chlordiazepoxide
NHCH3
N
Cl
C16H14ClN3O: 299.76
Chlordiazepoxide, when dried, contains not less than
98.5% and not more than 101.0% of chlordiazepoxide
(Cl6H14ClN3O).
Description Chlordiazepoxide is a white to pale yellow crystal or crystalline powder.
Chlordiazepoxide is freely soluble in glacial acetic acid,
sparingly soluble in ethanol, very lightly soluble in ether

Chlorodiazepoxide dissolves in dilute hydrochloric acid.
Chlorodiazepoxide is gradually affected by light.
solutions of Chlordiazepoxide and Chlordiazepoxide RS
in 0.1 mol/L hydrochloric acid TS (1 in 200000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Chlordiazepoxide and Chlordiazepoxide RS, previously dried, as directed in the potassium bromide disk method under the
(3) Proceed with Chlordiazepoxide as directed under
the Flame Coloration Test (2) and perform the test: a
green color develops.
Chlordiazepoxide according to Method 2 and perform
(2) Related substancePerform the test without exposure to daylight, using light-resistant vessels. Dissolve
0.20 g of Chlordiazepoxide in exactly 10 mL of a mixture of methanol and ammonia TS (97 : 3) and use this
solution as the test solution. Pipet 1 mL of the test solution, add a mixture of methanol and ammonia TS (97 : 3)
standard solution (1). Separately, dissolve 10 mg of 2amino-5-chlorobenzophenone RS in methanol to make
exactly 200 mL and use this solution as the standard solution (2). Perform the test with the test solution and the
standard solutions (1) and (2) as directed under the Thinlayer Chromatography. Spot 25 L of the test solution
and 5 L each of the standard solutions (1) and (2) on a
chromatography. Develop the plate with a mixture of
ethyl acetate and dehydrated ethanol (19 : 1) to a distance of about 12 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the
are not more intense than the spot from the standard solution (1). Spray evenly a solution of sodium nitrite in 1
mol/L hydrochloric acid TS (1 in 100) on the plate, allow
to stand for 1 minute and spray evenly N-(1-naphthyl)N'-diethyl-ethylenediamine oxalateacetone TS on the
plate: the spots from the test solution are not more intense than the spots from the standard solution (2).
P2O5, 60 C, 4 hours).
Assay Weigh accurately about 0.6 g of Chlordiazepox-
KP 9 189
ide, previously dried and dissolve in 50 mL of glacial

acetic acid. Titrate with 0.1 mol/L perchloric acid VS until the color of the supernatant liquid changes from purple through blue purple to blue (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.
chromatography. Proceed as directed in the Purity (2)
under Chlordiazepoxide.

= 29.976 mg of Cl6H14ClN3O
Particle Size Distribution Test It meets the requirement.

tight containers.
Chlordiazepoxide Powder
Chlordiazepoxide Powder contains not less than 93.0%
and not more than 107.0% of the labeled amount of
chlordiazepoxide (Cl6H14ClN3O: 299.76).
Powders, with Chlordiazepoxide.
Identification (1) Weigh a portion of Chlordiazepoxide Powder, equivalent to 10 mg of Chlordiazepoxide according to the labeled amount, add 100 mL of 0.1 mol/L
hydrochloric acid TS, shake and filter. To 5 mL of the filtrate, add 0.1 mol/L hydrochloric acid TS to make 100
mL, determine the absorption spectrum as directed under
the Ultraviolet-visible Spectrophotometry: it exhibits
maxima between 244 nm and 248 nm and between 306
nm and 310 nm and a minimum between 288 nm and
292 nm.
(2) Weigh a portion of Chlordiazepoxide Powder,
equivalent to 20 mg of Chlordiazepoxide according to
the labeled amount, add 10 mL of methanol, shake for 5
minutes, then filter by suction through a glass filter, evaporate the filtrate with the aid of a current of air to dryness and dry the residue in vacuum at 60 C for 1 hour.
Determine the infrared absorption spectrum of the residue as directed in the potassium bromide disk method
under the Infrared Spectrophotometry: it exhibits absorption at the wave numbers of about 1625 cm-1, 1465 cm-1,
1265 cm-1, 850 cm-1 and 765 cm-1.
Purity Related substancesPerform this test without
exposure to daylight, using light-resistant vessels, To a
portion of Chlordiazepoxide Powder, equivalent to 50
mg of Chlordiazepoxide according to the labeled amount,
add exactly 5 mL of a mixture of methanol and ammonia
TS (97 : 3), shake, centrifuge and use the supernatant
liquid as the test solution. Separately, dissolve 50 mg of
Chlordiazepoxide RS in a mixture of methanol and ammonia TS (97 : 3) to make exactly 50 mL and use this solution as the standard solution (1). Dissolve 5.0 mg of 2amino-5-chlorobenzophenone RS in methanol to make
exactly 200 mL and use this solution as the standard solution (2). Perform the test with the test solution and the
Uniformity of Dosage Units(divided) It meets the requirement.

Assay Perform this test without exposure to daylight,
using light-resistant vessels. Weigh accurately a quantity
of Chlordiazepoxide Powder, equivalent to about 0.1 g of
chlordiazepoxide (Cl6H14ClN3O), transfer to a glassstoppered flask, add exactly 90 mL of methanol, stopper,
shake vigorously for 15 minutes and centrifuge. Pipet 10
mL of the supernatant liquid, add exactly 5 mL of the internal standard solution, add methanol to make exactly
100 mL and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Chlordiazepoxide
RS, previously dried in a desiccator (in vacuum, P2O5,
o
60 C ) for 4 hours, dissolve in methanol, add exactly 5

mL of the internal standard solution, add methanol to
make exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L each of the
operating conditions and calculate the ratios, QT and
QS , of the peak area of Chlordiazepoxide to that of the

internal standard for the test solution and the standard solution, respectably.
Amount (mg) of chlordiazepoxide (Cl6H14ClN3O)
= amount (mg) of Chlordiazepoxide RS
QT
QS
Internal standard solutionA solution of isobutyl

salicylate in methanol (1 in 20),
about 25 C.
Mobile phase: A mixture of methanol and 0.02 mol/L
monobasic ammonium phosphate TS (7 : 3).
time of Chlordiazepoxide is about 5 minutes.
System suirability
with 10 L of the standard solution under the above operating conditions, Chlordiazepoxide and internal standard are eluted in this order with the resolution between
these peaks neing not less than 9.
times, the relative standard deviation of the ratios of the
peak area of Chlordiazepoxide to that of internal standard.
tight containers.
Preserve in light-resistance,
Chlordiazepoxide Tablets
Chlordiazepoxide Tablets contain not less than 93.0%
chlordiazepoxide (Cl6H14ClN3O: 299.76).
Method of Preparation Prepare as directed under Tablets, with Chlordiazepoxide.
Identification (1) Weigh a portion of powdered Chlordiazepoxide Tablets, equivalent to 10 mg of Chlordiazepoxide according to the labeled amount, add 100 mL of
0.1 mol/L hydrochloric acid TS, shake and filter. To 5
mL of the filtrate, add 0.1 mol/L hydrochloric acid TS to
make 100 mL. Determine the absorption spectrum of this
solution as directed under the Ultraviolet-visible absorption spectrophotometry: it exhibit the maximum absorption at the wavelength between 244 and 248 nm and the
minimum absorption at the wavelength 288 and 292 nm.
(2) Weigh a portion of powdered Chlordiazepoxide
Tablets, equivalent to 10 mg of Chlordiazepoxide according to the labeled amount, add 10 mL of ether, shake
vigorously and centrifuge. Evaporate 5 mL of the supernatant liquid by warming on a water-bath to dryness. Determine the infrared absorption spectrum of the residue
the Infrared Spectrophotometry: it exhibits absorption at
the wave numbers of about 1625 cm-1, 1465 cm-1, 1265
cm-1, 850 cm-1 and 765 cm-1.
Purity Related substancesPerform the test without
exposure to daylight, using light-resistant vessels, To a
portion of powdered Chlordiazepoxide Tablets, equivalent to 50 mg of Chlordiazepoxide according to the labeled amount, add exactly 5 mL of a mixture of methanol and ammonia TS (97 : 3), shake, centrifuge and use
the supernatant liquid as the test solution. Separately,
dissolve 50 mg of Chlordiazepoxide RS in a mixture of
methanol and ammonia TS (97 : 3) to make exactly 50
Dissolve 5.0 mg of 2-amino-5-chlorobenzophenone RS
in methanol to make exactly 200 mL and use this solution as the standard solution (2). Perform the test with the
test solution and the standard solutions (1) and (2) as directed under the Thin-layer Chromatography. Spot 25 L
of the test solution and 10 L each of the standard solutions (1) and (2) on a plate of silica gel with fluorescent
indicator for thin-layer chromatography. Proceed as directed in the Purity (2) under Chlordiazepoxide.
Dissolution Test
Perform the test with 1 tablet of
Chlordiazepoxide Tablets at 100 revolutions per minute
according to Method 2 under the Dissolution Test, using
900 mL of the Dissolution medium solution 2 as the dissolution solution. Take 30 mL or more of the dissolved
solution after 60 minutes from the start of the test and filter through a membrane filter with pore size of not more
than 0.8 m. Discard the first 10 mL of the filtrate, pipette the subsequent V mL, add the Dissolution medium
solution 2 to make exactly V' mL so that each mL contains about 3.7 g of chlordiazepoxide (Cl6H14ClN3O)
according to the labeled amount and use this solution as
mg of Chlordiazepoxide RS, previously dried in a desiccator for 4 hours (in vacuum, P2O5, 60 C) and dissolve
in the Dissolution medium solution 2 to make exactly
200 mL. Pipette 3 mL of this solution, add the Dissolution medium solution 2 to make exactly 50 mL and use
this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard solution, respectably, at 260 nm as directed under
The dissolution rate of Chlordiazepoxide Tablets in 60
minutes is not less than 70%.
Dissolution rate (%) with respect to the labeled of chlordiazepoxide (Cl6H14ClN3O)

= W S AT V ' 1 27
AS
WS : Amount (mg) of Chlordiazepoxide RS.

C: Labeled amount (mg) of chlordiazepoxide
(Cl6H14ClN3O) in 1 tablet.
Assay Perform the test without exposure to daylight,
using light-resistant vessels. Weigh accurately a portion
of powdered Chlordiazepoxide Tablets, equivalent to
about 0.1 g of chlordiazepoxide (Cl6H14ClN3O), transfer
to a glass-stoppered flask, add 10 mL of water and shake
well to disintegrate. Add 60 mL of methanol, shake well,
add methanol to make exactly 100 mL and centrifuge.
Pipet 10 mL of the supernatant liquid, add exactly 5 mL
of the internal standard solution, add methanol to make
Separately, weigh accurately about 10 mg of Chloroiazepoxide RS, previously dried in a desiccator (in vacuum,
P2O5, 60 C) for 4 hours, dissolve in 1 mL of water and
methanol, add exactly 5 mL of the internal standard solution, add methanol to make exactly 100 mL and use this
solution as the standard solution. and proceed as directed
in the assay under Chlordiazepoxide Powder.
KP 9 191
Amount (mg) of chlordiazepoxide (Cl6H14ClN3O)

= amount (mg) of Chlordiazepoxide RS
QT
10
QS
Internal standard solutionA solution of isobutyl

salicylate in methanol (1 in 20).
tight containers.
Chlordiazepoxide Hydrochloride
NHCH3
N
Cl
HCl
C16H14ClN3OHCl: 336.22
Chlordiazepoxide Hydrochloride contains not less than
98.0% and not more than 102.0% of chlordiazepoxide
hydrochloride (C16H14ClN3OHCl), calculated on the
dried basis.
Description
Chlordiazepoxide Hydrochloride is a
white crystalline powder and is odorless. Chlordiazepoxide Hydrochloride is soluble in water or in ethanol and
sparingly soluble in hexane.
Chlordiazepoxide Hydrochloride is affected by light.
Identification (1) To about 20 mg of Chlordiazepoxide
Hydrochloride, add 5 mL of hydrochloric acid and 10
mL of water and heat to boiling to hydrolyze. To the
cooled solution, add 2 mL of sodium nitrite solution (1 in
1000), 1 mL of ammonium sulfamate solution (1 in 200)
and 1 mL of N-1-naphthylethylenediamine dihydrochloride solution (1 in 1000): a reddish violet color is observed.
(2) The relative retention time of the major peak in
the chromatogram of the test solution corresponds to that
of the Standard solution obtained as directed in the Assay.
(3) Determine the infrared spectra of Chlordiazepoxide Hydrochloride and Chlordiazepoxide Hydrochloride
RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry:
Melting Point Between 212 C and 218 C (with decomposition).
Purity
(1) Heavy metalsProceed with 1.0 g of
Chlordiazepoxide Hydrochloride according to Method 1

(2) Related substancesTransfer about 50 mg of
Chlordiazepoxide Hydrochloride to a volumetric flask
and dissolve in 2.5 mL of acetone by shaking. Allow to
stand until precipitate and use the supernatant as the test
solution. Separately, weigh a portion of 7-Chloro-1,3dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one-4-oxide
RS, dissolve in acetone to make the concentration of 100
g per mL and use this solution as the standard solution
(1). Weigh a portion of 2-Amino-5-chlorobenzophenone
RS, dissolve in acetone to make the solution containing
10 g per mL and use this solution as the standard solution (2). Perform the test with the test solution and the
plate of silica gel for thin-layer chromatography. Develop the plate, previously not equilibrated with the developer, with ethyl acetate until the solvent front has moved
about three-fourths of the length of the plate, air-dry the
plate. Spray evenly 1 mol/L sulfuric acid in the plate, dry
the plate at 105 C for 15 minutes and then spray sodium
nitrite (1 in 1000), ammonium sulfamate (1 in 200) and
N-(1-naphthyl)ethylenediamine hydrochloric acid (1 in
1000) sequentially. The spots, equivalent to those from
the standard solutions, from the test solution are not
more intense than the spots from the standard solutions
(1) and (2).
P2O5, 60 C, 4 hours).
Assay Perform the test under the conditions protected
from light. Transfer about 0.1 g of Chlordiazepoxide Hydrochloride, accurately weighed, to a volumetric flask,
dissolve in mobile phase by sonicating for minutes, dilute with mobile phase to make 50 mL and mix. Transfer
10 mL of the resulting solution, dilute with mobile phase
to make 100 mL, mix and use this solution as the test solution. Separately, weigh a portion of Chlordiazepoxide
Hydrochloride RS and accurately dissolve in mobile
phase to make the concentration of 1 mg per mL. Pipet
10 mL of this solution, add mobile phase to make exactly
100 mL and use this solution as a standard solution. Perform the test with 5 L each of the test solution and the
standard solution and calculate the peak areas, AT and
AS , the test solution and the standard solution respectively.

Amount (mg) of Chlordiazepoxide Hydrochloride
(C16H14ClN3OHCl) = 0.5 C
AT
AS

C: Concentration of Chlordiazepoxide Hydrochloride
RS solution (g/mL).
(5 to 10 m in particle diameter).
40).
System suitability
with 5 L of the standard solution under the above operating conditions, the theoretical plates are not less than
3600, and the symmetry factor is no more than 2.0
above operating conditions, the relative standard deviation of the peak area of chlordiazepoxide hydrochloride
is not more than 2.0 %.
tight containers.
Capsules
(1 in 20000).
Dissolution Test Perform the test with 1 capsule of
Chlordiazepoxide Hydrochloride Capsules at 100 revolutions per minute according to Method 1 under the Dissolution Test, using 900 mL of water as a dissolution solution. Take the dissolved solution after 30 minutes from
the beginning of the test and filter through a membrane
filter with pore size of not more than 0.8 m. Pipet V
mL of the filtrate accurately, add water to make the concentration of about 6 g per mL with the volumes of V
weigh accurately 30 mg of Chlordiazepoxide Hydrochloride RS and dissolve in water to make exactly 100 mL.
Pipet 2 mL of this solution, add water to make exactly
Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 245 nm,
using water as the blank, as directed under the Ultraviolet-visible Spectrophotometry. Remove the contents of
12 Chlordiazepoxide Hydrochloride Capsules as completely as possible with the aid of a current of air, determine the absorbance at the same dilution and in the same
manner as for the Capsules and make any necessary
modifications.
The dissolution rate of Chlordiazepoxide Hydrochloride
Capsules in 30 minutes should be not less than 85%.
Dissolution rate (%) of the labeled quantity of chlordiazepoxide hydrochloride capsules (C16H14ClN3OHCl)
= WS
AT V ' 90 1
AS V
C 5
Chlordiazepoxide Hydrochloride Capsules contain not

less than 90.0% and not more than 110.0% of the labeled
amount
of
chlordiazepoxide
hydrochloride
(C16H14ClN3OHCl: 336.22).
WS: Amount of Chlordiazepoxide Hydrochloride RS

(mg),
C: Labeled quantity of chlordiazepoxide hydrochloride (C16H14ClN3OHCl) (mg).

Capsules, with Chlordiazepoxide Hydrochloride.

to following method.
Perform this procedure without exposure of daylight using light-resistant vessels. Transfer the contents of 1 capsule to a 200 mL volumetric flask, dissolve in and dilute
with water to volume, and filter, discarding the first 20
mL of the filterate. Dilute a portion of the filtrate quantitatively and step-wise with 0.1N hydrochloric acid to obtain a solution having a concentration of about 6 g of
Chlordiazepoxide Hydrochloride per mL. Dissolve a
suitable quantity of Chlordiszeposide Hydrocholride RS,
accurately weighed, in 0.1 N hydrochloric acid to obtain
a standard solution having a known concentration of
about 6 g per mL. Concomitantly determine the absorbances AT and AS of the test solution and the standard solution at the wavelength of maximum absorbance
of about 245nm, with a suitable spectrophotometer, using
0.1 mol/L hydrochloric acid as the blank.
Identification (1) The solution used for measurement

of absorbance in the Assay exhibits maxima at 245 2
nm and 311 2 nm and the ratio, A245 / A311 , is between 2.90 and 3.45.
(2) A portion of the contents of Chlordiazepoxide
Hydrochloride Capsules responds to Identification (1)
under Chlordiazepoxide Hydrochloride.
Purity Related substancesAccurately weigh a portion of Chlordiazepoxide Hydrochloride Capsules,
equivalent to about 25 mg of chlordiazepoxide hydrochloride (C16H14ClN3OHCl) and perform the test as directed in Purity (2) under Chlordiazepoxide Hydrochloride. Use 15 L of 7-chloro-1,3-dihydro-5-phenyl-2H1,4-benzodiazepin-2-one-4-oxide in acetone (1 in 1000)
and 10 L of 2-amino-5-chlorobenzophenone in acetone
KP 9 193
Calculate the quantity, in mg, of C16H14ClN3OHCl in the

A
Capsule by the formula = T C T
AS
T : Labeled amount (mg) of Chlordiazepoxide Hydrochloride in the 1 Capsule.

D : Concentration (g/mL) of Chlordiazepoxide Hydrochloride in the test solution, based on the labeled
amount per Capsule and the extent of dilution
C : Concentration (g/mL) of Chlordiazepoxide Hydrochloride RS in the standard solution
Assay Perform this procedure without exposure to daylight, using light-resistant vessels. Weigh accurately the
contents of not less than about 20 Chlordiazepoxide Hydrochloride Capsules and determine the average weight
per capsule. Mix the combined contents and transfer an
accurately weighed portion of the powder, equivalent to
about 60 mg of chlordiazepoxide hydrochloride
(C16H14ClN3OHCl), to a volumetric flask. Add methanol
to make 100 mL, mix and filter and discard the first 15
mL of the filtrate. Pipet 5 mL of the clear filtrate into a
volumetric flask and add sulfuric acid in ethanol (1 in
360) to make 100 mL. Pipet 10 mL of this solution into a
volumetric flask and dilute with sulfuric acid in ethanol
(1 in 360) to make 50 mL and use this solution as the test
solution. Dissolve an accurately a portion of Chlordiazepoxide Hydrochloride in methanol to obtain a solution
having a known concentration of about 60 mg per mL.
Dilute this solution quantitatively and step-wise with sulfuric acid in ethanol (1 in 360) to obtain a standard solution having a known concentration of about 6 g per mL.
Concomitantly determine the absorbances of the test solution and the standard solution at the wavelength of
maximum absorbance at about 245 nm, as directed under
the Ultraviolet-visible Spectrophotometry, using sulfuric
acid in ethanol (1 in 360) as the blank. Calculate the absorbances, AT and AS , for the test solution and the
Amount (mg) of chlordiazepoxide hydrochloride

A
(C16H14ClN3OHCl) = 10 C T
AS
C: Concentration of Chlordiazepoxide Hydrochloride

RS solution (g/mL).
for Injection
Chlordiazepoxide Hydrochloride for Injection is a prepa-
ration for injection which is reconstituted before use and

contains not less than 93.0% and not more than 107.0%
of the labeled amount of chlordiazepoxide hydrochloride
(C16H14ClN3OHCl: 336.22).
Method of Preparation Prepare as directed under Injections, with Chlordiazepoxide Hydrochloride.
Description Chlordiazepoxide Hydrochloride for Injection is a white crystalline powder and is odorless.
Chlordiazepoxide Hydrochloride for Injection is soluble
in water or in ethanol and sparingly soluble in hexane.
Chlordiazepoxide Hydrochloride for Injection is affected
by light.
Identification Perform the test, as directed under
Chlordiazepoxide Hydrochloride.
pH The pH of the solution containing about 1.0 g of
Chlordiazepoxide Hydrochloride for Injection in 100 mL
of water is between 2.5 and 3.5.
Purity Heavy metals and related substances Perform the tests according to Methods (1) and (2), as directed under Chlordiazepoxide Hydrochloride.
P2O5, 60 C, 4 hours).
Bacterial Endotoxins Less than 3.57 EU per 1 mg of
Chordiazepoxide Hydrochloride.
It

Assay Proceed as directed under Chlordiazepoxide
Hydrochloride.
Chlorhexidine Gluconate
Solution
Chlorhexidine Gluconate Solution is a solution of digluconate of chlorhexidine.
Chlorhexidine Gluconate Solution contains not less than
19.0 w/v% and not more than 21.0 w/v% of chlorhexidine gluconate (C22H30Cl2N102C6H12O7: 897.76).
Description Chlorhexidine Gluconate Solution is a

clear, colorless or pale yellow liquid, is odorless and has
a bitter taste.
Chlorhexidine Gluconate Solution is miscible with glacial acetic acid or with water.
One mL of Chlorhexidine Gluconate Solution is miscible
with not more than 5 mL of dehydrated ethanol or not
more than 3 mL of acetone. A white turbidity is produced
by further addition of dehydrated ethanol or acetone.
Chlorhexidine Gluconate Solution is gradually colored
by light.
20
Specific gravity d 20
: Between 1.06 and 1.07.
Identification (1) To 50 L of Chlorhexidine Gluconate Solution, add 5 mL of methanol, 1 mL of bromine
TS and 1 mL of 8 mol/L sodium hydroxide TS: a deep
red color is observed.
(2) To 0.5 mL of Chlorhexidine Gluconate Solution,
add 10 mL of water and 0.5 mL of cupric sulfate TS: a
white precipitate is produced. Heat to boiling: the precipitate changes to pale purple.
(3) To 10 mL of Chlorhexidine Gluconate Solution,
add 5 mL of water, cool on ice and add 5 mL of sodium
hydroxide TS dropwise with stirring: a white precipitate
is produced. Collect the precipitate by filtration, wash
with water, recrystalize from diluted ethanol (7 in 10)
and dry at 105 C for 30 minutes: the crystals thus obtained melt between 130 C and 134 C.
(4) Neutralize the filtrate obtained in (3) with 5
mol/L hydrochloric acid TS. To 5 mL of this solution,
add 0.65 mL of glacial acetic acid and 1 mL of freshly
distilled phenylhydrazine and heat in a water-bath for 30
minutes. After cooling, scratch the inner wall of the vessel with a glass rod to induce crystallization. Collect the
crystals, dissolve in 10 mL of hot water, add a small
amount of activated charcoal and filter. Cool the filtrate,
scratch the inner side of the vessel, collect the formed
crystals and dry: the crystals thus obtained melt at about
195 C (with decomposition).
pH Add 5.0 mL of Chlorhexidine Gluconate Solution
to water to make 100 mL: the pH of this solution is between 5.5 and 7.0.
Purity p-ChlroanilineTo 2.0 mL of Chlorhexidine
Gluconate Solution, add water to make exactly 100 mL.
Pipet 5 mL of the solution and add 20 mL of water and 5
mL of 1 mol/L hydrochloric acid TS. Add 0.3 mL of sodium nitrite TS, shake and allow to stand for 2 minutes.
Add 4 mL of ammonium sulfamate TS and then allow to
stand for 1 minute. Add 5 mL of N-(1-naphthyl)-Ndiethylethylenediamine oxalate-acetone TS, allow to
stand for 10 minutes, add 1 mL of ethanol and then add
water to make 50 mL: the color of the solution is not
more intense than the following control solution.
Control solutionDissolve 20 mg of p-chloroaniline

in 10 mL of 1 mol/L hydrochloric acid TS and add water
to make exactly 100 mL. Pipet 5 mL of the solution, add

20 mL of water and 5 mL of 1 mol/L hydrochloric acid
TS and proceed as directed for the preparation of the test
solution.
Residue on Ignition Not more than 0.1% (2 g, after
evaporation).
Assay Pipet 2 mL of Chlorhexidine Gluconate Solution,
evaporate to dryness on a water-bath, dissolve the residue in 60 mL of glacial acetic acid for nonaqueous titration and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 22.444 mg of C22H30Cl2N102C6H12O7
tight containers.
Chlorhexidine Hydrochloride
NH
Cl
NH
NH
NH
NH
NH(CH2)6NH
NH
NH
NH
Cl
2HCl
C22H30Cl2N102HCl: 578.37
Chlorhexidine Hydrochloride, when dried, contains not
less than 98.0% and not more than 101.0% of chlorhexidine hydrochloride (C22H30Cl2N102HCl).
Description Chlorhexidine Hydrochloride is a white,
Chlorhexidine Hydrochloride is soluble in formic acid,
slightly soluble in methanol or in warm methanol and
practically insoluble in water, in ethanol or in ether.
Chlorhexidine Hydrochloride is gradually affected by
light.
Identification (1) Dissolve 10 mg of Chlorhexidine
Hydrochloride in 5 mL of methanol by warming and add
1 mL of bromine TS and 1 mL of 8 mol/L sodium hydroxide TS: a deep red color is observed.
(2) Dissolve 0.3 g of Chlorhexidine Hydrochloride in
10 mL of 6 mol/L hydrochloric acid TS, cool in ice and
add 10 mL of 8 mol/L sodium hydroxide TS drop-wise
with stirring: a white precipitate is produced. Collect the
precipitate, wash with water, recrystallize from diluted
ethanol (7 in 10) and dry at 105 C for 30 minutes: the
crystals so obtained melt between 130 C and 134 C.
(3) Dissolve 0.1 g of Chlorhexidine Hydrochloride in
50 mL of dilute nitric acid: the solution responds to the
Purity
(1) Heavy metalsProceed with 2.0 g of
KP 9 195
Chlorhexidine Hydrochloride according to Method 2 and
(2) ArsenicTo 1.0 g of Chlorhexidine Hydrochloride in a crucible, add 10 mL of a solution of magnesium
nitrate in ethanol (1 in 10), fire the ethanol to burn and
heat gradually to incinerate. If a carbonized substance
remains, moisten with a small volume of nitric acid and
ignite to incinerate. Cool, add 10 mL of dilute hydrochloric acid to the residue, dissolve by warming in a waterbath, use this solution as the test solution and perform the
(3) p-ChloroanilineDissolve 0.10 g of Chlorhexidine Hydrochloride in 2 mL of formic acid and add 15
mL of 1 mol/L hydrochloric acid TS and 20 mL of water
immediately. Add 0.3 mL of sodium nitrite TS, shake
and allow to stand for 2 minutes. Add 4 mL of ammonium sulfamate TS and then allow to stand for 1 minute.
Add 5 mL of N-(1-naphthyl)-N-diethylethylene diamineoxalate-acetone TS, allow to stand for 10 minutes, add
1 mL of ethanol and then add water to make 50 mL: the
color of the solution is not more intense than the following control solution.
Control solutionDissolve 20 mg of p-chloroaniline

in 10 mL of 1 mol/L hydrochloric acid TS and add water
to make exactly 100 mL. Pipet 5 mL of the solution and
add water to make exactly 100 mL. To 2.0 mL of this solution, add 2 mL of formic acid, 15 mL of 1 mol/L hydrochloric acid TS and 20 mL of water and proceed in
the same manner.
hours).
Assay Weigh accurately 0.2 g of Chlorhexidine Hydrochloride, previously dried, dissolve in 2.0 mL of formic acid, add 60 mL of acetic anhydride and titrate with
0.1 mol/L perchloric acid VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). Perform a

= 14.459 mg of C22H30Cl2N102HCl
Chlormadinone Acetate
CH3
O
H3C
O
CO
OCCH3
H3C
O
H
Cl
C23H29C1O4: 404.93
Chlormadinone Acetate, when dried, contains not less
than 98.0% and not more than 101.0% of chlormadinone
acetate (C23H29C1O4).
Description Chlormadinone Acetate is a white to pale
yellow crystal or crystalline powder and is odorless.
Chlormadinone Acetate is freely soluble in chloroform,
soluble in acetonitrile, slightly soluble in ethanol or in
ether and practically insoluble in water.
Identification (1) Dissolve 2 mg of Chlormadinone
Acetate in 1 mL of ethanol and add 1 mL of mdinitrobenzene TS and 1 mL of a solution of potassium
hydroxide (1 in 5): a red-purple color develops.
(2) To 50 mg of Chlormadinone Acetate, add 2 mL of
potassium hydroxide-ethanol TS and boil in a water-bath
for 5 minutes. After cooling, add 2 mL of diluted sulfuric
acid (2 in 7) and boil gently for 1 minute: the odor of
ethylacetate is perceptible.
(3) Determine the infrared spectra of Chlormadinone
Acetate and Chlormadinone Acetate RS, previously dried,
the Infrared Spectrophotometry: both spectra exhibit
(4) Perform the test with Chlormadinone Acetate as
directed under the Flame Coloration Test (2): a green
color appears.
D : Between -10.0 C
and -14.0 C (after drying, 0.2 g, acetonitrile, 10 mL, 100
mm).
Melting Point between 211 C and 215 C.
Chlormadinone Acetate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
Chlormadinone Acetate according to Method 3 and perform the test (not more than 2 ppm).

(3) Related substancesDissolve 20 mg of Chlormadinone Acetate in 10 mL of acetonitrile and use this
solution as the test solution. Pipet 1 mL of the test solution, add acetonitrile to make exactly 100 mL and use
with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine each
method: the total area of peaks other than the peak of
Chlormadinone Acetate from the test solution is not larger than the peak area of Chlormadinone Acetate from the
standard solution.
about 30 C.
Mobile phase: A mixture of acetonitrile and water
(13 : 7).
time of Chlormadinone Acetate is about 10 minutes.
System suitability
Test for required detection: Pipet exactly 5 mL of
the standard solution, add acetonitrile to make exactly 50
mL. The peak area of Chlormadinone Acetate obtained
from 10 L of this solution is between 7 and 13% of the
peak area of Chlormadinone Acetate obtained from 10
L of the standard solution.
System performance: Dissolve 8 mg of Chlormadinone Acetate and 2 mg of butyl parahydroxybenzoate in
100 mL of acetonitrile. When the procedure is run with
10 L of this solution under the above operating conditions, butyl parahydroxybenzoate and chlormadinone
acetate are eluted in this order, with the resolution between their peaks being not less than 8.0.
System repeatability: When the test is repeated 6 times
above conditions: the relative standard deviation of the
peak areas of chlormadinone acetate is not more than
1.0%.
Time span of measurement: About 1.5 times as long
as the retention time of chlormadinone acetate after the
solvent peak.
P2O5, 4 hours).
Assay Weigh accurately about 20 mg each of Chlormadinone Acetate and Chlormadinone Acetate RS, previously dried, and dissolve in ethanol to make exactly
100 mL. Pipet 5 mL each of these solutions, add ethanol
to make exactly 100 mL and use these solutions as the

test solution and the standard solution, respectively. Perform the test with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry and determine the absorbance, AT and AS , at
285 nm, for the test solution and the standard solution,
respectively.
Amount (mg) of chlormadinone acetate (C23H29ClO4) =
amount (mg) of Chlormadinone Acetate RS
tight containers
AT
AS
Chlorothiazide
O
NH2SO2
O
S
NH
Cl
C7H6ClN3O4S2: 295.72
Chlorothiazide contains not less than 98.0% and not
more than 102.0% of chlorothiazide (C7H6ClN3O4S2)
Description
Chlorothiazide is a white crystalline
Chlorothiazide is very slightly soluble in water, freely
soluble in dimethyl formamide or in dimethyl sulfoxide,
slightly soluble in methanol or in pyridine, and practically insoluble in ether, in benzene or in chloroform.
solutions of Chlorothiazide and Chlorothiazide RS in sodium hydroxide solution (1 in 250) (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
both spectra exhibit the similar intensities of absorption
at the same wavelength and the difference of absorption
is not less than 3.0% when calculated on the dried basis
at the maximum absorption wavelength of about 292 nm.
(2) Determine the infrared absorption spectra of
Chlorothiazide and Chlorothiazide RS as directed in the
paste method under the Infrared Spectrophotometry: both
same wavenumbers.
Purity (1) ChlorideDissolve 1.0 g of Chlorothiazide
in a mixture of 10 mL of water and 10 mL of sodium hydroxide (1 in 10) solution. Cool in an ice-bath and add 20
mL of water and 5 mL of nitric acid: a flocculent, white
precipitate is formed. Titrate with 0.05 mol/L of silver nitrate (potentiometric titration, Endpoint Detection Me-
KP 9 197
thod in Titrimetry), using a silver-silver chloride electrode system: not more than 0.28 mL is required (not
more than 0.05%).
(2) Heavy metalsProceed with 1.0 g of Chlorothiazide according to Method 2 and perform the test.
(3) SeleniumUsing a solution of 0.20 g of Chlorothiazide in 25 mL of dilute nitric acid (1 in 30) in 1000
mL of oxygen flask as the absorbing liquid, proceed as
directed under Oxygen Flask Combustion Method. After
combustion, wash inside of the A, B and C with 10 mL
of water, transfer the solution of the oxygen flask to the
150 mL of beaker using 20 mL of water, heat slowly until boiling and then boil for 10 minutes, cool to the room
temperature and use this solution as the test solution.
Separately, take 6 mL exactly of the selenium standard
solution in 25 mL of dilute nitric acid (1 to 30) and 25
mL of water and use this solution as the standard solution.
After adjusting pH to 2.0 0.2 by adding ammonia solution (1 to 2) to each of the test solution and the standard solutions, dilute each solution with exactly 60 mL
of water, transfer to the each separatory funnel using
10.0 mL of water and wash each separatory funnel with
10.0 mL of water. After dissolving 0.2 g of hydroxylamine in this solution followed by addition of 5.0 mL of
2,3-diaminonaphtalene TS with stirring and closing with
stopper and stand for 100 minutes at room temperature.
After adding 5.0 mL of cyclohexane, shaking vigorously
for 2 minutes, standing, separating two layers, discard
aqueous layer and take cyclohexane layer, after water of
the cyclohexane extract is removed on centrifuge. Perform the test as directed under the Ultraviolet-visible
Spectrophotometry using the solution obtained according
to the same method by adding 25 mL of water to 25 mL
of dilute nitric acid as the reference solution. Absorbance
of the test solution when measured at near 380 nm at absorbance maximum wavelength is not larger than that
obtained from the standard solution (not more than
0.003%).
(4) 4-Amino-6-chloro-1,3-benzenedisulfonamide
Weigh accurately a portion of 4-amino-6-chloro-1,3benzenedisulfonamide RS dissolve in mobile phase, to
make each mL of mobile phase containing 1.5 g of 4amino-6-chloro-1,3-benzene-disulfonamide and use this
20 L each of the test solution obtained from the Assay
Chromatography according to the operating conditions
under the Assay: the amount of 4-amino-6-chloro-1,3benzene disulfonamide is not more than 1.0% when main
peak areas, AT and AS of 4-amino-6-chloro-1,3benzenedisulfonamide of the test solution and the standard solution, respectively, are measured.
Amount (mg) of 4-amino-6-chloro-1,3A
benzenedisulfonamide = 0 .2 C T
AS
C: Concentration (g/mL) of 4-Amino-6-chloro-1,3benzenedisulfonamide RS in standard solution.

hour).
Assay Weigh accurately about 30 mg of Chlorothiazide
in 200 mL of volumetric flask, put a volume of acetonitrile, not more than 10% of the total volume, add the mobile phase to make exactly 200 mL and use this solution
as the test solution. Separately, weigh a portion of Chlorothiazide RS and 4-Amino-6-chloro-1,3-benzenedisul
fonamide RS accurately, add the mobile phase to make
each mL contains 0.15 mg of Chlorothiazide and 1.5 g
of 4-amino-6-chloro-1,3-benzenedisulfonamide and use
with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine
the peak areas, AT and AS, of the test solution and the
standard solution, respectably.
Amount (mg) of Chlorothiazide (C7H6ClN3O4S2)

= 200 C
AT
AS
C: Concentration (mg/mL) of Chlorothiazide RS in the

standard solution.
octadesyl silanized silica gel for liquid chromatography
Mobile phase: A mixture of 0.1 mol/L sodium hydrogen phosphate and acetonitrile (9 : 1) whose pH is adjusted to 3.0 0.1 by adding phosphoric acid.
System suitability
with 20 L of the standard solution under the above operating conditions, 4-amino-6-chloro-1,3-benzenedisul
fonamide and chlorothiazide are eluted in this order with
the resolution of these peaks being not less than 3.5.
times with 20 L of the standard solution: the relative
standard deviation of the peak areas of chlorothiazide is
not more than 1.5%.
Chlorothiazide Tablets
Chlorothiazide Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of chlorothiazide (C7H6ClN3O4S2: 295.72).
Method of Preparation Prepare as directed under Tablets, with Chlorothiazide.
Identification (1) Powder 1 tablet of Chlorthiazide
Tablets and fuse with a pellet of sodium hydroxide: the
ammonia fumes produced turn moistened red litmus paper blue and the residue responds to the Qualitative Test
for sulfite.
(2) The retention time of the main peak obtained
from the test solution as directed in the Assay corresponds to that from the standard solution.
Dissolution Test Perform the test with 1 tablet of Chlorothiazide Tablets at 75 revolutions per minute according
0.05 mol/L phosphate buffer solution, pH 8.0, as a dissolution solution prepared from 50 mL of 0.2 mol/L potassium dihydrogen phosphate buffer solution, 42.3 mL of
0.2 mol/L sodium hydroxide and 200 mL of water. Take
a volume of dissolved solution after 60 minutes from the
start of the test, filter, dilute with a volume of dissolution
solution, if necessary and use this solution as the test solution. Separately, weigh accurately a portion of Chlorothiazide RS, previously dried at 105 C for 1 hour, dissolve in the dissolution solution to make same concentration as the test solution and use this solution as the standard solution. Determine the absorbances, AT and AS ,
of the test solution and the standard solution, respectively,
at 294 nm as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Chlorothiazide Tablets in 60 minutes is not less than 75%.
lution and the standard solution as directed under the

Liquid Chromatography according to the following operating conditions. Determine the peak areas, AT and AS ,
of the test solution and the standard solution, respectively.
Amount (mg) of chlorothiazide (C7H6ClN3O4S2)
= Amount (mg) of Chlorothiazide RS
AT
10
AS
octadesylsilanized silica gel for liquid chromatography
Mobile phase: A mixture of 0.08 mol/L sodium dihydrogen phosphate and methanol (95 : 5) whose pH is
adjusted to 2.9 0.1 by adding phosphoric acid.
System suitability
with 15 L of the standard solution under the above operating conditions, the symmetry factor is not more than
2.0.
times with 15 L of the standard solution: the relative
standard deviation of the peak areas of chlorothiazide is
not more than 2.0%.
Chlorphenesin Carbamate
Cl
OH
OCH2CHCH2O
NH2

Chlorothiazide Tablets. Weigh accurately a quantity of
powder, equivalent to about 0.25 g of chlorothiazide
(C7H6ClN3O4S2) in a volumetric flask, add 50 mL of 0.05
mol/L sodium dihydrogen phosphate and sonicate for
about 2 minutes. Add 100 mL of acetonitrile and sonicate
about for 3 minutes, dilute with water to make exactly
500 mL, mix, filter and use this solution as the test solution. Seperately, weigh accurately 25 mg of Chlorothiazide RS, previously dried at 105 C for 1 hour, add 5 mL
of 0.05 mol/L sodium dihydrogen phosphate, followed
by 20 mL of acetonitrile, sonicate with occasional shaking often about for 3 minutes. Add water to make exactly
50 mL, mix, filter and use this solution as the standard
solution. Perform the test with 15 L each of the test so-
Cl0H12ClNO4: 245.66
Chlorphenesin Carbamate, when dried, contains not less
than 98.0% and not more than 102.0% of chlorphenesin
carbamate(Cl0H12ClNO4 ).
Description Chlorphenesin Carbamate is a white crystal or crystalline powder, is odorless and has a slightly
bitter taste.
Chlorphenesin Carbamate is freely soluble in methanol,
in ethanol or in pyridine, soluble in isopropanol, sparingly soluble in ether, slightly soluble in water and practically insoluble in hexane.
A solution of Chlorphenesin Carbamate in ethanol (1 in
KP 9 199
solutions of Chlorphenesin Carbamate and Chlorphenesin Carbamate RS in ethanol (3 in 200000) as directed
same wavelengths.
(2) Determine the infrared spectra of Chlorphenesin
Carbamate and Chlorphenesin Carbamate RS, previously
(3) Perform the test with Chlorphenesin Carbamate
as directed under the Flame Coloration Test (2): a green
color appears.
Melting Point
Purity (1) Heavy metalsDissolve 2.0 g of Chlorphenesin Carbamate in 20 mL of ethanol and add 2 mL of
dilute acetic acid and water to make 50 mL. Perform the
control solution as follows: to 2.0 mL of standard lead
solution, add 20 mL of ethanol, 2 mL of dilute acetic acid
and water to make 50 mL (not more than 10 ppm).
Chlorphenesin Carbamate according to Method 3 and
(3) Related substances(i) Chlorphenesin-2carbamate: Dissolve 0.10 g of Chlorphenesin Carbamate
in 20 mL of a mixture of n-hexane for liquid chromatography and isopropanol(7 : 3) and use this solution as the
test solution. Perform the test with 10 L of the test solution as directed under the Liquid Chromatography according to the following conditions. Determine the peak
area, Aa , of Chlorphenesin Carbamate and the peak area,
Ab , of chlorphenesin-2-carbamate by the automatic integration method: the ratio, Ab /(Aa + Ab ) , is not larger
than 0.007.
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with silica gel for liquid chromatography (5 m in particle diameter).
Column temperature: At constant temperature.of
about 40 C.
Mobile phase: a mixture of n-hexane for liquid
chromatography, isopropanol and glacial acetic acid
(700 : 300 : 1)
time of Chlorphenesin Carbamate is about 9 minutes.
System suitability
Test for required detection: Pipet 1 mL of the test
solution, add a mixture of hexane for liquid chromatography and isopropanol (7 : 3) to make 100 mL, and use
this solution as the test solution in the system suitability.

The peak area of chlorphenesin carbamate obtained from
10 L of this solution is between 40 and 60% of the peak
area of chlorphenesin carbamate obtained from the test
solution of the system suitability.
System performance: Dissolve 0.1 g of Chlorphenesin Carbamate in methanol to make 50 mL. To 25 mL
of this solution, add 25 mL of dilute sodium hydroxide
TS and warm at 60 C for 20 minutes. To 20 mL of this
solution, add 5 mL of 1 mol/L hydrochloric acid TS,
shake well with 20 mL of ethylacetate, allow to stand to
separate the ethyl acetate layer and take the ethyl acetate
layer. When the procedure is run with 10 L of this solution under the above operating conditions, chlorphenesin,
chlorphenesin carbamate and chlorphenesin-2- carbamate are eluted in this order, with the ratios of the retention time of chlorphenesin and chlorphenesin-2carbamate to chlorphenesin carbamate being about 0.7
and about 1.2, respectively and with the resolution between the peaks of chlorphenesin and Chlorphenesin
Carbamate being not less than 2.0.
times with 10 L of the test solution in the system suitability under the above operation conditions, the relative
standard deviation of the peak area of chlorphenesin carbamate is not more than 2.0%.
(ii) Other related substances: Dissolve 0.10 g of
Chlorphenesin Carbamate in 10 mL of ethanol and use
solution and add ethanol to make exactly 20 mL. Pipet 2
mL of this solution, add ethanol to make exactly 20 mL
a plate of silica gel for liquid chromatography. Develop
the plate with a mixture of ethyl acetate, methanol and
strong ammonia water (17 : 2 : 1) to a distance of about
10 cm and air-dry the plate. Allow to stand in iodine vapor for 20 minutes: the spots other than the principal spot
from the test solution are not more intense than the spot
from the standard solution.
silica gel, 4 hours).
Assay Weigh accurately about 0.5 g of Chlorphenesin
Carbamate, previously dried, dissolve in 20 mL of pyridine, add exactly 50 mL of 0.1 mol/L potassium hydroxide-ethanol VS and warm at 70 C for 40 minutes. After
cooling, add 100 mL of ethanol and titrate the excess potassium hdroxide with 0.1 mol/L hydrochloric acid VS
until the color of the solution changes from blue through
blue-green to yellow (indicator: 1 mL of thymol blue TS).
correction.

= 24.566 mg of Cl0H12ClNO4
%
Absorbance E11cm
(after drying, 5 mg, 0.25 mol/L sulfuric acid TS, 250
mL).
Chlorpheniramine Maleate
N
CH2CH2N(CH3)2
CO2H
C
Cl
C
CO2H
and enantiomer
C16H19ClN2.C4H4O4: 390.86
Chlorpheniramine Maleate, when dried, contains not less
than 98.0% and not more than 101.0% of dlchlorpheniramine maleate (C16H19ClN2C4H4O4).
Description Chlorpheniramine Maleate is a white, fine
crystal, is odorless and has a bitter taste.
Chlorpheniramine Maleate is very soluble in glacial acetic acid, freely soluble in water or in methanol, and sparingly soluble in ethanol.
A solution of Chlorpheniramine Maleate shows no optical rotation.
solutions of Chlorpheniramine Maleate and Chlorpheniramine Maleate RS in 0.1 mol/L hydrochloric acid TS (1
(2) Determine the infrared spectra of Chlorpheniramine Maleate and Chlorpheniramine Maleate RS, previously dried, as directed in the paste method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers..
(3) Dissolve 0.1 g of Chlorpheniramine Maleate in 5
mL of methanol, and use this solution as the test solution.
Separately, dissolve 56 mg of maleinic acid in 10 mL of
methanol, and use this solution as the standard solution.
the Thin-layer Chromatography. Spot each 5 L of the
with a mixture of ether, methanol, glacial acetic acid and
water (70 : 20: 7 : 3) to a distance of about 12 cm and
air-dry the plates. And examine the plate under ultraviolet light (main wavelength: 254 nm): a spot among two
of the spots obtained from the test solution shows the
similar intense and same Rf value with the spot obtained from standard solution.
pH Dissolve about 1.0 g of Chlorpheniramine Maleate
in 100 mL of freshly boiled and cooled water: the pH of

1.0 g of Chlorpheniramine Maleate in 50 mL of water:
(2) Heavy metalsProceed with1.0 g of Chlorpheniramine Maleate according to Method 4, and perform the
lead solution (not more than 20 ppm).,.
(3) Related substancesDissolve 0.10 g of Chlorpheniramine Maleate in 100 mL of the mobile phase, and
of the test solution and add the mobile phase to make exactly 100 mL. Pipet exactly 2 mL of this solution, add
the mobile phase again to make exactly 20 mL and use
with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions; and determine each
peak area of both solutions according to the automatic integration method: the peak area other than the peak of
Maleic acid and Chlorpheniramine obtained from the test
solution is not larger than 2/3 times the peak area of
Chlorpheniramine obtained from the standard solution.
The total area of the peaks other than the peaks of maleic
acid and chlorpheniramine obtained from the test solution is not larger than the peak area of chlorpheniramine
obtained from the standard solution.
Detector: An ultraviolet absorption photometer
about 25 C.
Mobile phase: Dissolve 8.57 g of ammonium dihydrogen phosphate and 1 mL of phosphoric acid in water
to make 1000 mL. To 800 mL of this solution add 200
mL of acetonitrile.
time of chlorpheniramine is about 11 minutes.
System suitability
Test for required detectability: To exactly 2.5 mL
of the standard solution add the mobile phase to make
exactly 25 mL. Confirm that the peak area of chlorpheniramine obtained with 20 L of this solution is equivalent
with 20 L of the standard solution under the above operating conditions, the number o theoretical plates and
KP 9 201
the symmetry factor of the peak of chlorpheniramine are
not less than 40000 and not more than 2.0, respectively.
above operating conditions, the relative standard deviation of the peak area of chlorpheniramine is not more
than 4.0%.
as the retention time of chlorpheniramine after the solvent peak.
hours).
Assay Dissolve about 0.4 g of Chlorpheniramine Maleate, previously dried and accurately weighed, in 20 mL
of glacial acetic acid. Titrate with 0.1 mol/L perchloric
acid VS until the color of the solution changes from purple through blue-green to green (indicator: 2 drops of
methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.

= 19.543 mg of C16H19ClN2C4H4O4
tight containers.
d-Chlorpheniramine Maleate
N
CH2CH2N(CH3)2
H
Cl
C

+43.0 (after drying, 0.5 g, dimethylformamide, 10 mL,
100 mm).
pH Dissolve 1.0 g of d-Chlorpheniramine Maleate in
100 mL of freshly boiled and cooled water: the pH of
%
Absorbance E11cm
(after drying, 5 mg, 0.25 mol/L sulfuric acid TS, 250
mL).
CO2H
C
(2) Determine the infrared spectra of dChlorpheniramine Maleate and d-Chlorpheniramine Maleate RS, previously dried, as directed under Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(3) Dissolve 0.1 g of d-Chlorpheniramine Maleate in
5 mL of methanol, and use this solution as the test solution. Separately, dissolve 56 mg of maleic acid in 10 mL
of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot 5 L each of the
test solution and standard solution on a plate of silica gel
for thin-layer chromatography. Deveop the plate with a
mixture of ether, methanol, glacial acetic acid and water
(70 : 20 : 7 : 3) to a distance of about 12 cm, and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm), a spot among two of the spots obtained
from the test solution shows the same intense to the spot
with the stasndard solution, and its R value is about 0.4.
CO2H
C16H19ClN2C4H4O4: 390.86
d-Chlorpheniramine Maleate, when dried, contains not
less than 99.0% and not more than 101.0% of dchlorpheniramine maleate (C16H19ClN2C4H4O4).
Description d-Chlorpheniramine Maleate is a white,
crystal powder, is odorless and has a bitter taste.
d-Chlorpheniramine Maleate is very soluble in methanol
or in glacial acetic acid, and freely soluble in imethylformamide or in ethanol.
d-Chlorpheniramine Maleate is dissolves in dilute hydrochloric acid.
solutions of d-Chlorpheniramine Maleate and dChlorpheniramine Maleate RS in hydrochloric acid TS (3
in 100000) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths

g of d-Chlorpheniramine Maleate in 50 mL of water: the
solution is colorless and clear.
(2) Heavy metalsProceed 1.0 g of dChlorpheniramine Maleate according to Method 4, and
perform the test.Prepare the control solution with 2.0 mL
of standard lead solution (not mre than 20 ppm).
(3) Related substancesDissolve 0.10 g of dChlorpheniramine Maleate in 100 mL of the mobile
phase, and use this solution as the test solution. Pipet 3
mL of the test solution, and add the mobile phase to
the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 20 L each of the test solution and standard solution as directed under Liquid Chromatography according
to the following conditions; and determine each peak
area by the automatic integration method: the peak area
other than maleic acid and chlorpheniramine is not larger
than 2/3 times thepeak area of chlorpheniramine obtained
from the standard solution, and the total area of the peaks
other than maleic acid and chlorpheniramine is not larger
than the peak area of chlorpheniramine with the standard
solution.
(10 L in particle diameter).
about 25.
Mobile phase: Dissolve 8.57 g of ammonium dihydrogen phosphate and 1 mL of phosphoric acid in water
to make 1000 mL. To 800 mL of this solution add 200
mL of acetonitrile.
System suitability
Test for required detectability: To exactly 2.5 mL
of the standard solution add the mobile phase to make
exactly 25 mL. Confirm that the peak area of chlorpheniramine obtained from 20 L of this solution is equivalent
the symmetry factor of the peak of chlorpheniramine are
not less than 4000 and not more than 2.0, respectively.
above operating conditions, the relative standard deviation of the peak area of chlorpheniramine is not more
than 4.0%.
as the retention time of chlorpheniramine after the solvent peak.
hours).
Residue on Ignition
Assay Weigh accurately 0.3 g of d-Chlorpheniramine

Maleate, previously dried, and dissolve in 20 mL of glacial acetic acid. Titrate with 0.1 mol/L perchloric acid VS
until the color of the solution changes from purple
through blue-green to green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination

= 19.543 mg of C16H19ClN2C4H4O4
tight containers.
Injection
Chlorpheniramine Maleate Injection is an aqueous solution for injection.
Chlorpheniramine Maleate Injection contains not less
amount of dl-chlorpheniramine maleate (C16H19ClN2
C4H4O4: 390.86).
Method of Preparation Prepare as directed under Injections, with Chlorpheniramine Maleate.
Description Chlorpheniramine Maleate Injec-tion is a
Identification Take a volume of Chlorpheniramine
Maleate Injection, equivalent to 25 mg of Chlorpheniramine Maleate according to the labeled amount, add 5 mL
of dilute sodium hydroxide TS, and extract with 20 mL
of hexane. Wash the hexane layer with 10 mL of water,
shake with 0.5 g of anhydrous sodium sulfate for several
minutes, and filter. Evaporate the filtrate in a water bath
at 50 under a reduced pressure, anddetermine the
infrared absorption spectrum of the residue as directed in
the liquid film method under Infrared Chromatography:
it exhibits absorption at the wavenumbers of about 2940
cm-1, 2810 cm-1, 2770 cm-1, 1589 cm-1, 1491 cm-1, 1470
cm-1, 1434 cm-1, 1091 cm-1 and 1015-1 cm .
Bacterial Endotoxins Less than 8.8 EU per each mg
of Chlorpheniramine Maleate.
Insoluble Particulate Matter for Injections
the requirement.
It meets

Assay Transfer an exactly measured volume of Chlorpheniramine Maleate Injection, equivalent to about 3 mg
of chlorpheniramine maleate (C16H19ClN2.C4H4O4), to a
separator, add 20 mL of water and 2 mL of sodium hydroxide TS and extract with two 50 mL volumes of ether.
Combine the ether extracts, wash with 20 mL of water,
and then extract with 20-mL, 20-mL and 5-mL portions
of 0.25 mol/L sulfuric acid TS successively. Combine all
acid extracts, and add 0.25 mol/L sulfuric acid TS to
make exactly 200 mL. Pipet exactly 20 mL of this solution , transfer to a 100-mL separator, add 2 mL of sodium
KP 9 203
hydroxide TS, and extract with two 50-mL portions of
ether. Proceed in the same manner as for the preparation
of the test solution, and use the solution as the standard
solution. Determine the absorbances AT and AS of
the test solution and standard solution at a wavelength of
the maximum absorbance at about 265 nm as directed
under Ultraviolet-visible Spectrophotometry.
Amount (mg) of chlorpheniramine maleate
(C16H19ClN2C4H4O4)
= amount (mg) of Chlorpheniramine Maleate RS
AT
1
AS 10

Chlorpheniramine Maleate Powder contains not less than

of dl-chlorpheniramine maleate (C16H19ClN2C4H4O4:
390.86).
Powders, with Chlorpheniramine Maleate.
Identification Weigh a portion of Chlorpheniramine
Maleate Powder, equivalent to 50 mg of Chlorpheniramine Maleate according to the labeled amount, shake
with 40 mL of 0.1 mol/L hydrochloric acid TS, and filter.
Transfer the filtrate to a separator, and wash 40 mL of
hexane. Add 10 mL of sodium hydroxide TS, and extract
with 20 mL of hexane. Wash the hexane layer with 5 mL
of water. Centrifuge, if necessary, shake the hexane extract with 0.5 g of anhydrous sodium sulfate for several
minutes, and filter. Evaporate the filtrate in a water bath
under reduced pressure, and determine the spectrum of
the residue as directed in the liquid film method under
Infrared Spectrophotometry: it exhibits absorption at the
wavenumber of about 2940 cm-1, 2810 cm-1, 2770 cm-1,
1589 cm-1, 1491 cm-1, 1470 cm-1, 1434 cm-1, 1091 cm-1
and 1015 cm-1.
Uniformity of Dosage Units (divided)

quirement.

(C16H19ClN2C4H4O4)
= amount (mg) of chlorpheniramine maleate RS
Powder
Particle Size Distribution Test for Preparations

nutes, then add the internal standard solution to make exactly 100 mL, and use this solution as the test solution.
Separately, weigh accurately about 20 mg of Chlorpheniramine Maleate RS, previously dried at 105 for 3
hours, and add the internal standard to make exactly 100
mL. Pipet 20 mL of this solution, add the internal standard solution to make exactly 100 mL, and use this solution as the standard solution. Perform the test with 30 L
each of thetest solution and standard solution as directed
under Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS ,
of the peak area of chlorpheniramine to that of the internal standard.
It
It meets the re-
Assay Weigh accurately an amount of Chlorpheniramine Maleate Powder, equivalent to about 4 mg of

chlorpheniramine maleate (C16H19ClN2.C4H4O4), add 70
mL of the internal standard solution, shake for 15 mi-
QT 1
QS 5
Internal standard solutionTo 7 mL of a solution of

methyl parahydroxybenzoate in methanol (1 in 1000) add
water to make 1000 mL.
about 40 C.
Mobile phase: Dissolve 1.0 g of sodium 1-heptane
sulfonate in 900 mL of water, add 10 mL of glacial acetic
acid and water to make 1000 mL. To 650 mL of this solution add 350 mL of acetonitrile.
System suitability
with 30 L of the standard solution under the above operating conditions, the internal standard and chlorpheniramine are eluted in this order with the resolution between these peaks being not less than 2.0.
above operating conditions, the relative standard deviation of the ratio of the peak area of chlorpheniramine to
Range of measurement: About 4 times as long as the retention time of chlorpheniramine after the solvent peak.

Tablets
Chlorpheniramine Maleate Tablets contain not less than
of dl-chlorpheniramine maleate (C16H19ClN2C4H4O4:
390.86).
Method of Preparation Prepare as directed under Tablets, with Chlorpheniramine Maleate.
Identification Weigh a portion of powdered Chlorpheniramine Maleate Tablets, equivalent to 50 mg of Chlorpheniramine Maleate according to the labeled amount,
shake with 40 mL of 0.1 mol/L hydrochloric acid TS and
filter. Transfer the filtrate to a separator and wash with
40 mL of hexane. Add 10 mL of sodium hydroxide TS
and extract with 20 mL of hexane. Wash the hexane layer
with 5 mL of water. Centrifuge, if necessary, shake the
hexane extract with 0.5 g of anhydrous sodium sulfate
for several minutes and filter. Evapolate the filtrate in a
water bath at about 50 under reduced pressure, and
determine the spectrum of the residue as directed in the
liquid film method under Infrared Spectrophotometry: it
exhibits absorption at the wavenumber of about 2940 cm1
, 2810 cm-1 , 2770 cm-1 , 1589 cm-1 , 1491 cm-1, 1470
cm-1 , 1434 cm-1 , 1091 cm-1 and 1015 cm-1 .
Uniformity of Dosage Units Perform the test according to the following method: it meets the requirement of
the Content uniformity test.
To 1 tablet of Chlorpheniramine Maleate Tablets add 10
mL of water, shake to disintegrate the tablet, then add
water to make exactly V mL of a solution containing
about 80 g of chlorpheniramine maleate (C16H19ClN2
C4H4O4) per mL, and filter through a membrane filter
with pore size of not more than 0.5 um. Pipet 5 mL of the
filtrate, add exactly 2.5 mL of internal standard solution,
add water to make 10 mL, and use this solution as the
of Chlorpheniramine Maleate RS, previously dried at
105 for 3 hours, and add water to make exactly 100
mL. Pipet 20 mL of this solution, add exactly 25 mL of
the internal standard solution, add water to make 100 mL,
the test with 30 L each of the test solution and the standard solution as directed under Liquid Chromatography
according to the conditions described in the Assay, and
determine the ratios, QT and QS , of the peak area of
chlorpheniramine to that of the internal standard.

(C16H19ClN2C4H4O4)
QT
V
QS 250

methyl parahydroxybenzoate (1 in 250) add water to
make 1000 mL.
Assay Weigh accurately and Weigh accurately the mass
of not less than 20 Chlorpheniramine Maleate Tablets,
and powder. Weigh accurately a portion of the powder,
equivalent to about 4 mg of chlorpheniramine maleate
(C16H19ClN2.C4H4O4), add 70 mL of the internal standard
solution, shake for 15 minutes, then add the internal
standard solution to make exactly 100 mL, filter through
a membrane filter with pore size of not more than 0.5 m,
and use this solution as thetest solution. Separately,
weigh acculately about 20 mg of Chlorpheniramine Maleate RS, previously dried at 105 for 3 hours, and add
the internal standard to make exactly 100 mL. Pipet 20
mL of this solution, add the internal standard solution to
make exactly 100 mL, and use this solution as the standard solution. Perform the test with 30 L each of the
test solution and standard solution as directed under Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS , of the peak
area of chlorpheniramine to that of this internal standard.

(C16H19ClN2.C4H4O4)
QT 1
QS 5

methyl parahydroxybenzoate in methanol (1 in 1000) add
Column: Astainless steel column, about 4.6 mm in inside diameter and about 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
40 C.
sulfonate in 900 mL of water, add 10 mL of glacial acetic
acid and water to make 1000 mL. To 650 mL of this solution add 350 mL of acetonitrile.
System suitability
with 30 L of the standard solution under the above operating conditions, the internal standard and chlorpheni-
KP 9 205
ramine are eluted in this order with the resolution between these peaks being not less than 2.0.
above operating conditions, the relative standard deviation of the ratio of the peak area of chlorpheniramine to
Range of measurement: About 4 times as long as
the retention time of chlorpheniramine after the solvent
peak.
Packaging and Storage Preserve in tight containers..
within 10 minutes: the pH of this solution is between 4.0

and 5.0.
Purity (1) Clarity and color of solution A solution
of 1.0 g of Chlorpromazine Hydrochloride in 20 mL of
water, when observed within 10 minutes, is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 1.0 g of Chlorpromazine Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
hours).
Chlorpromazine Hydrochloride
CH3
CH2CH2CH2N
N
CH3
Cl
HCl
C17H19ClN2SHCl: 355.33
Chlorpromazine Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of chlorpromazine hydrochloride (C17H19ClN2SHCl).
Description Chlorpromazine Hydrochloride is a white
to pale yellow, crystalline powder, is odorless and has a
faint, characteristic odor.
Chlorpromazine Hydrochloride is very soluble in water,
freely soluble in ethanol or in glacial acetic acid, sparingly soluble in acetic anhydride and practically insoluble in
ether.
Chlorpromazine Hydrochloride is gradually colored by
light.
Identification (1) To 5 mL of a solution of Chlorpromazine Hydrochloride (1 in 1000), add 1 drop of ferric
chloride TS: a red color is observed.
(2) Dissolve 0.1 g of Chlorpromazine Hydrochloride
in 20 mL of water and 3 drops of dilute hydrochloric acid,
add 10 mL of picric acid TS and allow to stand for 5
hours. Collect the resulting precipitate, wash with water,
recrystallize from a small volume of acetone and dry at
105 C for 1 hour: the crystals so obtained melt between
175 C and 179 C.
(3) Dissolve 0.5 g of Chlorpromazine Hydrochloride
in 5 mL of water, add 2 mL of ammonia TS and heat in a
water-bath for 5 minutes. Cool, filter and render the filtrate acidic with dilute nitric acid: the solution responds
to the Qualitative Tests (2) for chloride.
pH Dissolve 1.0 g of Chlorpromazine Hydrochloride in
20 mL of freshly boiled and cooled water and measure

Assay Weigh accurately 0.7 g of Chlorpromazine Hydrochloride, previously dried, dissolve in 50 mL of a

= 35.533 mg of C17H19ClN2S HCl
tight containers.
Injection
Chlorpromazine Hydrochloride Injection is an aqueous
solution for injection and contains not less than 95.0%
chlorpromazine
hydrochloride
(C17H19ClN2SHCl:
355.33).
Method of Preparation Prepare as directed under Injections, with Chlorpromazine Hydrochloride.
Description Chlorpromazine Hydrochloride Injection
is a clear, colorless or pale yellow liquid.
Identification (1) Proceed with a volume of Chlorpromazine Hydrochloride Injection, equivalent to 5 mg
of Chlorpromazine Hydrochloride according to the labeled amount, as directed in the Identification (1) under
Chlorpromazine Hydrochloride.
(2) Proceed with a volume of Chlorpromazine Hydrochloride Injection, equivalent to 0.1 g of Chlorpromazine Hydrochloride according to the labeled amount, as
directed in the Identification (2) under Chlorpromazine

Hydrochloride.
It
Determination of Volume of Inhection in Containers

Assay Transfer an exactly measured volume of Chlorpromazine Hydrochloride Injection, equivalent to about
0.15 g of chlorpromazine hydrochloride (C17H19ClN2S
HCl), to a separator, add 30 mL of water and 10 mL of a
solution of sodium hydroxide (1 in 5) and extract with
two 30 mL volumes and three 20 mL volumes of ether.
Wash the combined ether extracts with successive 10 mL
volumes of water until the last washing shows no red
color upon the addition of phenolphthalein TS. Concentrate the ether extracts on a water-bath to 20 mL, add 5 g
of anhydrous sodium sulfate, allow to stand for 20 minutes and filter through a pledget of absorbent cotton.
Wash with ether, combine the washings with the filtrate
and evaporate the ether on a water-bath. Dissolve the residue in 50 mL of acetone and 5 mL of glacial acetic acid
color of the solution changes from red-purple to bluepurple (indicator: 3 drops of bromocresol green methylrosaniline chloride TS). Perform a blank determination

= 17.767 mg of C17H19ClN2SHCl
hermetic containers or color containers.
Syrup
Chlorpromazine Hydrochloride Syrup contains, in each
100 mL, not less than 0.19 g and not more than 0.21 g of
chlorpromazine
hydrochloride
(C17H19ClN2SHCl:
355.33).
Method of Preparation Prepare as directed under Syrups, with Chlorpromazine Hydrochloride.
Identification (1) Transfer a volume of Chlorpromazine Hydrochloride Syrup, equivalent to about 20 mg of
Chlorpromazine Hydrochloride, to a separator. Add 10
mL of water and 2 mL of sodium hydroxide solution (1
in 2) and mix. Extract with three 30 mL volumes of ether.
Filter the combined ether extracts through anhydrous sodium sulfate. With the aid of a stream of nitrogen, evaporate the ether to about 5 mL. Quantitatively transfer the
solution to a centrifuge tube. Evaporate with a stream of
nitrogen and mild heat to dryness. Dissolve the residue in
100 mL of methanol to obtain and use this solution as the
test solution. Separately, dissolve a suitable amount of
Chlorpromazine RS in methanol to have a concentration
of about 0.2 mg per mL, and use this solution as the
standard solution.
Perform the test as with these solutions directed under
the Thin-layer chromatography. Spot 15 L of the test
solution and standard solution on a plate of silica gel for
freshly prepared mixture of ethyl acetate that has been
saturated with ammonium hydroxide, ether and methanol
(75 : 25 : 20) to a distance of about 15 cm. Remove the
plate from the chamber, air-dry and spray with iodoplatinate reagent. The Rf value of the principal spot from
the test solution corresponds to that obtained from the
standard solution.
(2) Dilute a volume of the Chlorpromazine Hydrochloride Syrup with an equal volume of water: the resulting solution responds to Qualitative Tests for chloride.
Iodoplatinate reagentThis reagent is prepared by

dissolving 0.1 g of platinic chloride in 10 mL of 0.1
mol/L hydrochloric acid, adding 25 mL of potassium
iodide solution (1 in 25), 0.5 mL of formic acid and diluting with water to make 100 mL.
Purity Chlorpromazine sulfoxide Transfer an accurately measured volume of the Syrup, equivalent to about
20 mg of chlorpromazine hydrochloride, to a 125 mL separator. Add 10 mL of water and 2 mL of sodirm hydroxide solution (1 in 2), and mix. Extract with three 30 mL
portions of ether. Filter the combined ether extracts
through anhydrous sodium sulfate. With the aid of stream
of nitrogen evaporate the ether to about 5 mL. Quantitatively transfer the solution to a 40 mL centrifuge tube.
Evaporate with a stream of nitrogen and mild heat to
dryness. Dissolve the residue in 1.0 mL of methanol and
use this solution as test solution. Transfer 5 mL of a solution in dilute hydrochloric acid (1 in 100) of Chlorpromazine Hydrochloride RS containing 10.6 mg per mL
to a 50 mL volumetric flask. Add 2 mL of 30% hydrogen
peroxide and heat at 60 C for 10 minutes. Cool, dilute
with 1 mol/L sodium bisulfite solution to volume, and
mix. Transfer 10.0 mL of this solution to a 60 mL separator, add 2 mL of sodium hydroxide solution (1 in 2), and
mix. Extract with three 30 mL portions of ether. Filter the
extracts through ether-wetted anhydrous sodium sulfate
into a 250 mL conical flask. Cautiously evaporate the extracts to dryness. Dissolve the residue in 10.0 mL of methanol, and filter if necessary, and used this solution as
Chlorpromazine Sulfoxide standard solution. Each mL of
this solution contains 1 mg of chlorpromazine sulfoxide.
the Thin-layer chromatography. Spot 15 L each of the
KP 9 207
test solution and the Chlorpromazine sulfoxide standard
solution to a plate prepared of silica gel for the thin-layer
chromatography. Develop the plate with a freshly prepared mixture of ethyl acetate that has been saturated
with ammonium hydroxide, ether, and methanol (75 :
25 : 20) until the solvent front has moved about threefourths of the length of the plate. Remove the plate from
the chamber, air-dry, and spray with Iodoplatinate reagent. The chromatogram from the Test solution may exhibit a secondary spot whose Rf value corresponds to,
and whose size and intensity are not greater than, those
of the spot from the Clorpromazine sulfoxide standard
solution (5.0%).
Iodoplatinate reagentThis reagent is prepared by

dissolving 0.1 g of platinic chloride in 10 mL of 0.1
mol/L hydrochloric acid, adding 25 mL of potassium
iodide solution (1 in 25), 0.5 mL of formic acid and diluting with water to make 100 mL.
Chlorpromazine Hydrochloride Syrup, equivalent to
about 10 mg of chlorpromazine hydrochloride
(C17H19ClN2SHCl), to a volumetric flask, add 0.1 mol/L
hydrochloric acid to make 50 mL and mix. Transfer 10
mL of this solution to a separator, add about 20 mL of
water and strong ammonia water to make alkaline and
extract with four 25 mL volumes of ether. Extract the
combined ether layers with 25 mL of 0.1 mol/L hydrochloric acid. Transfer the aqueous layers to a volumetric
flask, evaporate ether, add 0.1 mol/L hydrochloric acid to
make 250 mL, mix and use this solution as the test solution. Separately, weigh accurately a portion of Chlorpromazine Hydrochloride RS, previously dried at 105 C
for 2 hours, dissolve in 0.1 mol/L hydrochloric acid TS
to make a solution containing 8 g/mL and use this solution as the standard solution. Determine the absorbances
of the test solution and the standard solutions, respectively, at 254 nm and 277 nm, using 0.1 mol/L hydrochloric
acid TS as the blank, as directed under the Ultravioletvisible Spectrophotometry.
Amount (mg) of chlorpromazine hydrochloride

(C17H19ClN2SHCl) in each mL of the syrup
= 1.25 C
( A254 -A277 ) T
( A254 -A277 ) S
C: Concentration of Chlorpromazine hydrochloride in

the standard solution (g/mL),
V: Volume of Chlorpromazine Hydrochloride Syrup
taken (mL),
( A254-A277 )T : Absorbance of the test solution,
( A254-A277 )S : Absorbance of the standard solution.

Tablets
Chlorpromazine Hydrochloride Tablets contain not less
amount of chlorpromazine hydrochloride (C17H19ClN2S
HCl: 355.33).
Method of Preparation Prepare as directed under Tablets, with Chlorpromazine Hydrochloride.
Identification (1) Shake a portion of powdered Chlorpromazine Hydrochloride Tablets, equivalent to 0.2 g of
Chlorpromazine Hydrochloride according to the labeled
amount, with 40 mL of 0.1 mol/L hydrochloric acid TS
and filter. To 1 mL of the filtrate, add 4 mL of water and
1 drop of ferric chloride TS: a red color is observed.
(2) To 20 mL of the filtrate obtained in (1), add 10
mL of picric acid TS drop-wise and proceed as directed
in the Identification (2) under Chlorpromazine Hydrochloride.
Dissolution Test Perform the test with 1 tablet of
Chlorpromazine Hydrochloride Tablets at 75 revolutions
per minute according to Method 2 under the Dissolution
Test, using 900 mL of the Dissolution medium solution 2
as a dissolution solution. Take 20 mL or more of the dissolved solution after 30 minutes from the start of the
Dissolution Test and filter through a membrane filter
with pore size of not more than 0.8 m. Discard the first
10 mL of the filtrate, pipet the subsequent V mL, add the
Dissolution medium solution 2 to make exactly V mL so
that each mL of the filtrate contains about 5.6 g of
chlorpromazine hydrochloride (C17H19ClN2SHCl) according to the labeled amount and use this solution as the
of Chlorpromazine Hydrochloride RS, previously dried
at 105 C for 2 hours, dissolve the Dissolution medium
solution 2 to make exactly 200 mL. Pipet 5 mL of this
solution, add the Dissolution medium solution 2 to make
exactly 100 mL, further pipet 5 mL of this solution, add
the Dissolution mediun solution 2 to make exactly 20 mL
the absorbances, AT and AS , of the test solution and
the standard solution, respectively, at 254 nm as directed
under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Chlorpromazine Hydrochloride
Tablets in 30 minutes should be not less than 75%.

of chlorpromazine hydrochloride
(C17H19ClN2SHCl) = W S AT V ' 1 45
AS
WS : Amount (mg) of Chlorpromazine Hydrochloride

RS.
C: Labeled amount (mg) of chlorpromazine hydrochloride (C17H19ClN2SHCl) in 1 tablet.

Assay Perform the procedure without exposure to daylight using the light-resistant vessels. Weigh accurately
and powder not less than 20 Chlorpromazine Hydrochloride Tablets. Weigh accurataly a portion of the powder,
equivalent to about 50 mg of chlorpromazine hydrochloride (C17H19ClN2SHCl), add 60 mL of a mixture of dilute phosphoric acid (1 in 500) and dehydrated ethanol,
treat with sonicator for 5 minutes, add a mixture (1:1) of
dilute phosphoric aicd (1 in500) and dehydrated ethanol
after mixed with strongly shaking, add a mixture (1:1) of
dilute phosphoric aicd (1 in500) and dehydrated ethanol
to make exactly 100 mL, filtrate with membrain filter
with a pore size not exceeding 0.45 m. Discard the first
3 mL of the filtrate, take the subsequent 2.5 mL, add exactly 5 mL of the internal standard solution, add a mixture (1:1) of dilute with phosphoric aicd (1 in500) and
dehydrated ethanol to make exactly 25 mL, and use this
about 25 mg of Chlorpromazine Hydrochloride RS, previously dried at 105 C for 2 hours, dilute with a mixture
(1:1) of dilute phosphoric aicd (1 in500) and dehydrated
ethanol to make exactly 100 mL. To exactly 5 mL of this
solution, add exactly 5 mL of the internal standard solution, dilute with a mixture (1:1) of dilute phosphoric aicd
(1 in500) to make exactly 25 mL and use this solution as
under the Liquid Chromatography according to the following operating conditions. And calculate the ratios,
QT and QS , of the peak area of chlorpromazine hydrochloride to that of the internal standard, for the test
Amount (mg) of chlorpromazine hydrochloride

(C17H19ClN2SHCl) = amount (mg) of Chlorpromazine
Hydrochloride RS QT
QS
Internal standard solutionA solution ethylparahydroxybenzoate in a mixture of diluted phosphoric acid (1

in 500) and dehydrated ethanol (1 : 1) (1 in 4500).
Column: A stainless steel column, about 4 mm in inside diameter and 15 to 30 cm in length, packed with
cyano groups chemically bonded silica gel for liquid
chromatography (5 m to10 m in particle diameter).
about 25 C.
Mobile phase: A mixture of diluted 0.05 mol/L so-
dium dihydrogen phosphate TS (1 in 2) and acetonitrile

(27 : 13).
time of Chlorpromazine hydrochloride is about 6.5 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, the internal standard and chlorpromazine are eluted in this order with the resolution between
these peaks the resolution being not less than 10.
System repeatability : When the test is repeated 6
above operating conditions, the relative standard deviation of the ratio of the peak area of chlorpromazine to
tight containers.
Chlorpropamide
Cl
SO 2NHCONHCH 2CH 2CH 3
C10Hl3ClN2O3S: 276.74
Chlorpropamide, when dried, contains not less than
98.0% and not more than 101.0% of chlorpropamide
(C10Hl3ClN2O3S).
Description Chlorpropamide is a white crystal or crystalline powder.
Chlorpropamide is freely soluble in methanol or in acetone, soluble in ethanol and slightly soluble in ether and
Identification (1) Dissolve 80 mg of Chlorpropamide
and Chlorpropamide RS in 50 mL of methanol, then to 1
mL each of these solutions, add 0.01 mol/L hydrochloric
acid TS to make 200 mL and determine the absorption
spectrum of solutions as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Chlorpropamide
and Chlorpropamide RS, previously dried, as directed in
(3) Perform the test with Chlorpropamide as directed
under the Flame Coloration Test (2): a green color appears.
Melting Point
Purity (1) AcidTo 3.0 g Chlorpropamide, add 150
KP 9 209
mL of water and warm at 70 C for 5 minutes. Allow to
stand in ice-water for 1 hour and filter. To 25 mL of the
filtrate, add 2 drops of methyl red TS and 0.30 mL of 0.1
mol/L sodium hydroxide VS: a yellow color develops.
(2) ChlorideTo 40 mL of the filtrate obtained in
(1), add 6 mL of dilute nitric acid and water to make 50
(4) Heavy metalsProceed with 2.0 g of Chlorpropamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(5) Related substancesDissolve 0.60 g of Chlorpropamide in acetone to make exactly 10 mL and use this
solution as the test solution. Pipet 1 mL of the test solution, add acetone to make exactly 300 mL and use this
solution as the standard solution (1). Separately, dissolve
60 mg of p-chlorobenzene sulfonamide in acetone to
make exactly 300 mL and use this solution as the standard solution (2). Perform the test with the test solution
and the standard solutions (1) and (2) as directed under
test solution, the standard solutions (1) and (2) on a plate
plate with a mixture of cyclohexane, isoamyl alcohol,
methanol and strong ammonia water (15 : 10 : 5 : 1) to a
distance of about 10 cm and air-dry the plate. After drying the plate at 100 C for 1 hour, spray evenly sodium
hypochlorite TS on the plate and air-dry for 15 minutes.
Then spray evenly potassium iodide-starch TS on the
plate: the spot from the test solution equivalent to the
spot from the standard solution (2) is not more intense
than the spot from the standard solution (2) and the spots
other than the spot mentioned above and other than the
principal spot from the test solution is not more intense
than the spot from the standard solution (1).
hours).
Assay Weigh accurately about 0.5 g of Chlorpropamide, previously dried, dissolve in 30 mL of neutralized
ethanol and add 20 mL of water. Titrate with 0.1 mol/L

= 27.674 mg of C10Hl3ClN2O3S
Chlorpropamide Tablets
Chlorpropamide Tablets contain not less than 95.0% and
not more than 105.0% of the labeled amount of chlorpropamide (C10Hl3ClN2O3S: 276.74).
Method of Preparation Prepare as directed under Tablets, with Chlorpropamide.
Identification Take a quantity of powdered Chlorpropamide Tablets, equivalent to 80 mg of Chlorpropamide
according to the labeled amount, add 50 mL of methanol,
shake and filter. To 1 mL of the filtrate, add 0.01 mol/L
hydrochloric acid TS to make 200 mL and determine the
absorption spectrum of this solution as directed under the
Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 231 nm and 235 nm.
Chlorpropamide Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of diluted phosphate buffer solution, pH 6.8, (1
in 2) as a dissolution solution. Take 20 mL or more of the
dissolved solution 45 minutes after starting the test and
filter through a membrane filter with pore size of not
more than 0.8 m. Discard the first 10 mL of the filtrate,
pipet the subsequent V mL of the nitrate, add diluted
phosphate buffer solution, pH 6.8, (1 in 2) to make exactly V' mL so that each mL contains about 10 g of chlorpropamide (C10Hl3ClN2O3S) according to the labeled
amount and use this solution as the test solution. Separately, weigh accurately about 50 mg of Chlorpropamide
RS, previously dried at 105 C for 3 hours, dissolve in 10
mL of methanol and add water to make exactly 50 mL.
Pipet 1 mL of this solution, add diluted phosphate buffer
solution, pH 6.8, (1 in 2) to make exactly 100 mL and
absorbances, AT and AS, of the test solution and the standard solution, respectively, at 232 nm as directed under
The dissolution rate of Chlorpropamide Tablets in 45 minutes should be not less than 70%.
Dissoution rate (%) with respect to the amount of chlorpropamide (C10Hl3ClN2O3S)

= WS
AT V ' 1
18
AS V C
WS : Amount (mg) of Chlorpropamide RS.

C: Labeled amount (mg) of chlorpropamide
(C10Hl3ClN2O3S) in 1 tablet.

Chlorpropamide Tablets. Weigh accurately a quantity of
the powder, equivalent to about 50 mg of chlorpropamide (C10Hl3ClN2O3S), add 75 mL of the mobile phase,
shake for 10 minutes and add the mobile phase to make
exactly 100 mL. Centrifuge this solution, pipet 10 mL of
the supernatant liquid, add the mobile phase to make exactly 100 mL and use this solution as the test solution.
Separately, weigh accurately about 50 mg of Chlorpropamide RS, previously dried at 105 C for 3 hours and
dissolve in the mobile phase to make exactly 100 mL.
Pipet 10 mL of this solution, add the mobile phase to
operating conditions. Determine the peak areas, AT
and AS , of Chlorpropamide of the test solution and the
Amount (mg) of chlorpropamide (C10Hl3ClN2O3S)
= amount (mg) of Chlorpropamide RS
AT
AS
Detector:An ultraviolet absorption photometer (wavelength: 240 nm).
about 25 C.
Mobile phase: A mixture of diluted glacial acetic acid
(1 in 100) and acetonitrile (1 : 1).
time of chlorpropamide is about 5 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, the numbers of theoretical plates are
not less than 1500 plates, and the symmetry factor of the
peak of chlorpropamide are not less than 1500 and not
more than 1.5, respectively.
above operating conditions, the relative standard deviation of the peak areas of chlorpropamide is not more than
1.5%.
Chlorzoxazone
Cl
NH
C7H4ClNO2: 169.57
Chlorzoxazone contains not less than 98.0% and not
more than 102.0% of chlorzoxazone (C7H4ClNO2), calculated on the dried basis.
Description Chlorzoxazone is white to pale yellow
crystals or crystalline powder, is odorless, tasteless and a
little irritant.
Chlorzoxazone is freely soluble in dimethylformamide,
soluble in methanol, in ethanol or in acetone, slightly soluble in ether and practically insoluble in water.
solutions of Chlorzoxazone and Chlorzoxazone RS in
methanol (1 in 50000) as directed under the Ultravioletvisible Spectrophotometry: the maximum and minimum
absorption occurs at the same wavelength.
(2) Determine the infrared spectra of Chlorzoxazone
and Chlorzoxazone RS, previously dried, as directed in
Chlorzoxazone according to Method 2 and perform the
(2) Related substancesWeigh accurately a portion
of Chlorzoxazone, dissolve in methanol, so that each mL
contains 20 mg of Chlorzoxazone and use this solution as
the test solution. Separately, weigh accurately a portion
of 2-Amino-4-chlorophenol RS, previously dried at 105
C for 2 hours and dissolve in methanol so that each mL
contains 100 g and 50 g of Chlorzoxazone and use
these solutions as the standard solutions (1) and (2). Perform the test with the test solution and the standard solutions and (1) and (2) as directed under the Thin-layer
and the standard solutions (1) and (2) on a plate of silica
with a mixture of hexane and dioxane (63 : 37) to a distance of about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the
are not more intense than the spot from the standard solution (1) (not more than 0.5 %). Also allow to stand in
iodine vapor: the spots other than the principal spot from
the test solution are not more intense than the spot from
the standard solution (2) (not more than 0.25 %).
hours).
KP 9 211
Assay Weigh accurately 50 mg of Chlorzoxazone and
Chlorzoxazone RS, previously dried at 105 C for 2
hours, dissolve in methanol and dilute with methanol to
make exactly 100 mL, respectively. Transfer each 4.0 mL
of these solutions to a volumetric flask and dilute with
methanol to make 100 mL and use these solutions as the
test solution and the standard solution, respectively. Perform the test with each of the test solution and the standard solution as directed under the Ultraviolet-visible
Spectrophotometry using methanol as a blank and determine the absorbances at 282 nm, AT and AS , of the
test solution and the standard solution, respectively.
Amount (mg) of chlorzoxazone (C7H4ClNO2)

= Amount (mg) of Chlorzoxazone RS
AT
AS
Packaging and Storage Preserve in tight container.
Chlorzoxazone Tablets
Chlorzoxazone Tablets contains not less than 90.0 % and
not more than 110.0 % of the labeled amount of chlorzoxazone (C7H4ClNO2: 169.56).
Method of Preparation Prepare as directed under Tablets, with Chlorzoxazone.
solutions (2 in 100000) of Chlorzoxazone and Chlorzoxazone RS in methanol as directed under the Ultravioletvisible Spectrophotometry: the maximum and minimum
absorption occurs at the same wavelength.
(2) The retention time of the main peak obtained as
directed in the Assay from the test solution corresponds
to the standard solution.
Dissolution Test
Perform the test with 1 tablet of
Chlorzoxazone Tablets at 75 revolutions per minute according to Method 2 under the Dissolution Test, using
1800 mL of phosphate buffer solution, pH 6.8 as a dissolution solution. Take a portion of dissolved solution after
60 minutes of the test, filter, discard the first 10 mL of
the filtrates and use next filtrate as the test solution. Separately, weigh accurately a portion of Chlorzoxazone RS,
previously dried at 105 C for 2 hours, dissolve in the
dissolution solution to make the same concentration as
that of the test solution and use this solution as the standard solution. Perform the test with the test solution and
the standard solution as directed under Assay.
The dissolution rate of Chlorzoxazone Tablets in 60 minutes is not less than 75%.

Chlorzoxazone Tablets. Weigh accurately a portion of
powder, equivalent to about 0.125 g of chlorzoxazone
(C7H4ClNO2) in a volumetric flask, add about 70 mL of
acetonitrile and shake vigorously for 30 minutes. Dilute
with acetonitrile to make exactly 100 mL and filter. Discard the first 10 mL of the filtrates, transfer 5 mL of next
filtrate to a volumetric flask containing 10.0 mL of internal standard solution, dilute with diluted glacial acetic
acid (1 in 100) to make exactly 50 mL, mix and use this
0.125 g of Chlorzoxazone RS, previously dried at 105 C
for 2 hours, add a volume of acetonitrile to make exactly
100 mL and use this solution as the standard stock solution. Transfer 5 mL of this solution to a volumetric flask
containing 10.0 mL of internal standard solution, dilute
with diluted glacial acetic acid (1 in 100) to make 50 mL,
mix and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following operating conditions
and calculate the ratios, Q T and QS of the peak area
of chlorzoxazone to that of the internal standard, for the
Amount (mg) of chlorzoxazone (C7H4ClNO2)

= amount (mg) of Chlorzoxazone RS
QT
QS
Internal standard solutionDilute 0.125 g of phenacetin with acetonitrile to make 100 mL.
Mobile phase: A mixture of water, acetonitrile and
glacial acetic acid (70 : 30 : 1).
System suitability
System performance: Dissolve 85 mg of pchlorophenol in 10 mL of acetonitrile. Transfer 1 mL of
this solution to a volumetric flask containing 4 mL of the
stock solution, 10 mL of the internal standard solution
and diluted glacial acetic acid (1 in 100) to make 50 mL
and mix. Proceed with this solution under the above operating conditions: phenacetin, chlorzoxazone and pchlorphenol are eluted in this order and the resolution between the cloxazone peak and the p-chlorophenol peak is
not less than 2.0.
times with 20 l of the standard solution: the relative

standard deviation of the peak areas of Chlorzoxazone is
not more than 1.5%.
Cholecalciferol
H
CH 3
H3C
H 3C
CH 3
CH 2
H
HO
H
Vitamin D3
C27H44O: 384.65
Cholecalciferol contains not less than 97.0% and not

more than 103.0% of cholecalciferol (C27H44O).
Description Cholecalciferol is a white crystal and is
odorless.
Cholecalciferol is freely soluble in ethanol, in chloroform, in ether or in isooctane, and practically insoluble in
water.
Cholecalciferol is affected by air and by light.
Melting pointBetween 84 C and 88 C.
Place Cholecalciferol in a capillary, dry for 3 hours in a
desicator (vacuum, not exceeding 2.67 kPa), fire seal the
capillary tube immediately, put it in a bath fiuid previously heated to a temperature of about 10 C beolw the
expected melting point, and heat at a rate of rise of about
3 per minute, and read the melting point.
Identification (1) Dissolve 0.5 mg of Cholecalciferol
in 5 mL of chloroform, add 0.3 mL of acetic anhydride
and 0.1 mL of sulfuric acid, and mix under shaking: a red
color is produced, and rapidly changes through purple
and blue to green.
(2) Determine the infrared absorption spectra of Cholecalciferol and Cholecalciferol RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
+ 112 (50 mg, ethanol, 10 mL, 100 mm). Prepare the solution without delay, using Cholecalciferol from a container opened not longer than 30 minutes previously, and
determine the rotation within 30 minutes after the solution has been prepared.
%
Absorbance E11cm
(10 mg, ethanol, 1000 mL).
Purity
7-DehydrocholesterolDissolve 10 mg of
Cholecalciferol in 2.0 mL of diluted ethanol (9 in 10),
add a solution prepared by dissolving 20 mg of digitonin
in 2.0 mL of diluted ethanol (9 in 10), and allow the mixture to stand for 18 hours: no precipitate is formed.
Assay Dissolve separately about 30 mg each of Cholecalciferol and Cholecalciferol RS, accurately weighed, in
isooctane to make exactly 50 mL. Pipet 10 mL each of
these solutions, add 3 mL each of the internal standard
solution, then add the mobile phase to make 50 mL, and
use these solutions as the test solution and the standard
solution, respectively. Perform the test with 10 L each
under the Liquid Chromatography according to the following conditions, and calculate the ratios, QT and QS ,
of the peak area of cholecalciferol to that of the internal
standard for the test solution and the standard solutions,
respectively. Proceed with the operation avoiding contact
with air or other oxidizing agents, and using lightresistant containers.
Amount (mg) of cholecalciferol (C27H44O)

= amount (mg) of Cholecalciferol RS QT
QS
Internal standard solutionA solution of dimethyl

phthalate in isooctane (1 in 100).
Column: A stainless steel column, about 4 mm in inside diameter and 10 cm to 30 cm in length, packed with
silica gel for liquid chromatography (5 m to 10 m in
particle diameter).
Mobile phase: A mixture of hexane and namylalcohol (997 : 3).
time of Cholecalciferol is about 25 minutes.
Selection of column: Dissolve 15 mg of Cholecalciferol RS in 25 mL of isooctane. Transfer this solution to
a flask, heat under a reflux condenser in an oil-bath for 2
hours, and cool to room temperature rapidly. Transfer
this solution to a quartz test tube, and irradiate under a
short-wave lamp (main wavelength: 254 nm) and a longwave lamp (main wavelength: 365 nm) for 3 hours. To
this solution, add the mobile phase to make 50 mL. Proceed with 10 L of this solution under the above operating conditions. Use a column with the ratios of the retention time of previtamin D3, trans-vitamin D3, and tachysterol D3 to that of cholecalciferol being about 0.5, about
0.6, and about 1.1, respectively, and with resolution between previtamin D3 and trans-vitamin D3, and that between cholecalciferol and tachysterol D3 being not less
than 1.0.
KP 9 213
hermetic containers under nitrogen atmosphere, and in a
cold place.
Chorionic Gonadotrophin
Chorionic Gonadotrophin is dried preparation of gonadstimulating hormone obtained from the urine of pregnant
women through the removal of the virus or non-active
process. . Chorionic Gonadotrophin contains not less
than 2500 chorionic gonadotrophin units per mg. Chorionic Gonadotrophin contains not less than 80.0% and
not more than 125.0% of the labeled amount of Chorionic Gonadotrophin.
Description Chorionic Gonadotrophin is a white to
pale yellow-brown powder.
Chorionic Gonadotrophin is odorless.
Chorionic Gonadotropin is freely soluble in water and
Identification Calculate b by the following equation,
using Y3 and Y4 obtained in the Assay: b is less than
120.
E
I
Y3 Y4
E=
f
b=
f : Number of test animals per group.

I = log
TH
TL
Purity (1) Clarity and color solutionDissolve 0.05 g

of Chorionic Gonadotrophin in 5 mL of isotonic sodium
chloride solution: the solution is clear and colorless or
pale yellow.
(2) EstrogenInject subcutaneously into each of
three female albino rats or albino mice ovaectomized at
least two weeks before the test, single dose of 100 units
according to the labeled units dissolved in 0.5 mL of isotonic sodium chloride solution. Take vaginal smear twice
daily, on the third, fourth and fifth day. Place the smear
thinly on a slide glass, dry, stain with Giemsas TS, wash
with water and again dry: no estrus figure is shown microscopically.
Loss on Drying Less than 5.0% (0.1 g, in vacuum,
phosphorus pentoxide, 4 hours).
Bacterial Endotoxins Less than 0.03 EU per each unit
of Chorionic Gonadotrophin.
Abnormal Toxicity Weigh the suitable amount of
Chorionic Gonadotrophin, prepare a solution containing
120 units per each mL, and use this solution as the test
solution. Inject 5.0 mL of the test solution into the peritoneal cavity of each of two or more of, well nourished,
healthy guinea pigs weighing about 350 g and observe
the conditions of the animals for more than days : all the
animals exhibit no abnormalities.
Specific activity When calculate from the results obtained by the Assay and the following test, the specific
activity is not less than 3000 human chorionic gonadotrophin Units per mg protein
(1) Test solutionTo an exactly amount of Chorionic Gonadotrophin add water to make a solution so that
each mL contains about 500 Units of chorionic gonadotrophin according to the labeled amount
(2) Standard solutionWeigh accurately about 10mg
of bovine serum albumin, and dissolve in water to make
exactly 20mL. To a suitable volume of this solution add
water to make four solutions containing exactly 300, 200,
100 and 50g of the albumin per mL, respectively.
(3) ProcedurePipet 0.5mL each of the test solution
and the standard solutions, put them in glass test tubes
about 18mm in inside diameter and about 130 mm in
length, add exactly 5mL of alkaline copper TS, mix, and
allow the tubes to stand in a water bath at 30 for 10
minutes. Then add exactly 0.5mL of diluted Folins TS
(1 in 2), mix, and warm in a water bath at 30 for 20
minutes. Determine the absorbances of these solutions at
750nm as directed under Ultraviolet-visible Spectrophotometry using a solution obtained in the same manner
with 0.5mL of water as the blank.
Plot the absorbances of the standard solutions on the vertical axis and their protein concentrations on the horizontal axis to prepare a calibration curve, and determine the
protein content of the test solution from its absorbance
by using this curve. Then calculate the amount of the
protein in the sample.
Assay (1) Test animalsSelect healthy female albino
rats weighing about 45 g.
(2) Standard solutionDissolve a quantity of Chorionic Gonadotrophin RS in bovine serum albuminisotonic sodium chloride solution to prepare four kinds
of solutions, having 7.5, 15, 30 and 60 units per 2.5 mL,
respectively. Inject these solutions into four groups consisting of five test animals each and weigh their ovaries,
as directed in procedure of (iv). Inject bovine serum albumin-isotonic sodium chloride solution to another
group and use this group as the control group. According
to the result of this test, designate the concentration of
the RS which will increase the weights of the ovaries
about 2.5 times the weight of the ovaries of the control
group as a low-dose concentration of the standard solution and the concentration 1.5 to 2.0 times the low-dose
concentration as a high dose concentration. Dissolve a
quantity of chorionic gonadotrophin RS in bovine serum
albumin-isotonic sodium chloride solution and prepare a
high-dose standard solution, S H and a low-dose stan-
dard solution, SL , whose concentrations are equal to

those determined by the above test.
(3) Test solutionAccording to the labeled units,
weigh accurately a suitable quantity of Chorionic Gonadotrophin, dissolve in bovine serum albumin-isotonic sodium chloride solution and prepare a high-dose sample
solution, TH and a low-dose test solution, TL , having
units equal to the standard solutions in equal volumes,
respectively.
(4) ProcedureDivide the test animals at random into 4 groups, A, B, C and D, with not less than 10 animals
and equal numbers in each group. Inject subcutaneously
0.5 mL of S H , SL , TH , TL in each group for 5 days.
On the sixth day, excise the ovaries and remove the adhering water by lightly pressing between filter paper and
immediately weigh the ovaries.
(5) CalculationDesignate the weight of ovaries by
S H , SL , TH , TL as y1 , y2 , y3 and y4 , respectively. Sum up y1 , y2 , y3 and y4 on each set to obtain Y1 , Y2 , Y3 and Y4 .
Units per mg of Chorionic Gonadotrophin
= antilog M (units per mL of the high dose of the standard solution)
M =
I = log
b
a
IYa
Yb
SH
T
= log H
SL
TL
Ya = Y1 Y2 + Y3 + Y4
s2 =
y2 f
n
y 2 : The sum of the squares of each
y1 , y2 , y3
and y4 .
Y = Y12 + Y22 + Y32 + Y42
n = 4( f 1)
L = 2 (C 1)(CM 2 + I 2 )
C=
Yb2
Yb2 4 fs 2 t 2
t 2 = Value shown in the following tablet against n
used to calcuate s2.
t 2 = F1
1
2
3
4
5
6
7
8
9
10
11
12
161.45
18.51
10.129
7.709
6.608
5.987
5.591
5.318
5.117
4.965
4.844
4.747
13
14
15
16
17
18
19
20
21
22
23
24
t 2 = F1
4.667
4.600
4.543
4.494
4.451
4.414
4.381
4.351
4.325
4.301
4.279
4.260
n
25
26
27
28
29
30
40
60
120
t 2 = F1
4.242
4.225
4.210
4.196
4.183
4.171
4.085
4.001
3.920
3.841

tight containers in a cold place.
Yb = Y1 Y2 + Y3 Y4
a: Mass (mg) of sample,
b: Total volume (mL) of the high dose of the test solution prepared by diluting with bovine serum albuminisotonic sodium chloride solution.
Chorionic Gonadotrophin
for Injection
F compared by the following equation should be

2
smaller than F1 against n when s is calculated.

And compute L (P = 0.95) by the following equation:
L should be not more than 0.3. If F exceeds F1 , or
if L exceeds 0.3, repeat the test increasing the number
of the test animals ro arranging the assay method in a
better way until F is smaller than F or L is not
more than 0.3.
F =
(Y1 Y2 Y3 + Y4 ) 2
4 fs 2
F : Number of test animals per group.
Chorionic Gonadotrophin for Injection is a preparation

for injection which is reconstituted before use. Chorionic
Gonadotrophin for Injection contains not less than 80.0%
and not more than 125.0% of the labeled units of Chorionic Gonadotrophin.
Method of Preparation Prepare as directed under Injections, with Chorionic Gonadotrophin.
Description Chorionic Gonadotrophin for Injection is
a white to pale yellow-brown powder or masses.
Chorionic Gonadotropin is freely soluble in water.
KP 9 215
under Chorionic Gonadotrophin.
(0.2 g calculated on the anhydrous basis, 0.067 mol/L

phosphate buffer solution at pH 7.0, 50 mL, 100 mm).

P2O5, 4 hours).
Bacterial Endotoxins Less than 0.03 EU per each mL
of Chorionic Gonadotrophin.
It meets the re-
Insoluble Particulate Matter Test

quirement.
Insoluble Particulate Matter Test for Injections It

Assay Proceed as directed in the Assay under Chorionic Gonadotrophin. The ratio of the assayed units to the
labeled units should be calculated by the following equation.
The ratio of the assayed units to the labeled units

= antilog M
hermetic containers in a cold place.
Cilazapril Hydrate
O
H
N
O
H3C
CO2H
H2O
N
N
C22H31N3O5,H2O : 435.51
Cilazapril Hydrate contains not less than 98.5% and not
more than 101.5% of cilazapril (C22H31N3O5), calculated
Description Cilazapril Hydrate is a white, crystalline
powder.
Cilazapril Hydrate is freely soluble in methanol or in methylene chloride, and slightly soluble in water.
spectra of Cilazapril Hydrate and Cilazapril Hydrate RS
20
[ ]365
nm : 383 to 399
Purity (1) Related substance I Dissolve 0.20 g of

Cilazapril Hydrate in methanol to make 5 mL, and use
this solution as the test solution. Separately, dissolve 2
mg of cilazapril related substance I RS {1,1dimethylethyl(1S,9S)-9-[[(S)-1-(ethoxycarbonyl)-3phenylpropyl]amino]-10-oxooctahydro-6H-pyridazino[1,
2-][1,2]diazepine-1-carboxylate}, accurately weighed,
in methanol to make exactly 50 mL, and use this solution
as the standard solution (1). Dissolve 5 mg of cilazapril
hydrate related substance I RS and 5 mg of Cilazapril
Hydrate in methanol to make exactly 10 mL, and use this
Chromatography. Spot 5 L each of the test solution , the
standard solution (1), and the standard solution (2) on a
plate of silica gel for thin-layer chromatography, develop
with a mixture of ethyl acetate, methanol, hexane, glacial
acetic acid, and water (60 : 15 : 15 : 5 : 5) to a distance of
about 10 cm, and dry the plate in air. Spray the plate first
with a freshly prepared mixture of 12 w/v% acetic acid
and potassium iodobismuthate solution (10:1) and then
with hydrogen peroxide TS. Any spot, corresponding to
the related substance I, from the test solution is not more
intense than the spot from the standard solution (1)
(0.1%). The test is valid when the chromatogram obtained with the standard solution (2) shows 2 clearly separated spots.
(2) Other related substances Dissolve 25 mg of
Cilazapril Hydrate, accurately weighed, in the mobile to
make 50 mL, and use this solution as the test solution.
Dilute 1.0 mL of the test solution to 50 mL with the mobile phase. Dilute 5.0 mL of this solution to 20 mL with
the mobile phase, and use this solution as the standard
solution (1). Separately, dissolve 10 mg of cilazapril hydrate related substance IV RS {(1S,9S)-9-[[(R)-1(ethoxycarbonyl)-3-phenylpropyl]amino]-10-oxoocta
hydro-6H-pyridazino-[1,2-][1,2]diazepine-1-carboxylic
acid}in the test solution to make exactly 20 mL, and use
with 20 L each of the test solution and the standard solutions as directed under the Liquid Chromatography according to the following conditions. In the chromatogram
obtained with the test solution: the area of any peak corresponding to the related substance IV is not greater than
0.4 times the area of the principal peak from the standard
solution (1) (0.2%); the area of any peak corresponding
to cilazapril hydrate related substance II {(1S,9S)-9-[[(S)1-carboxy-3-phenylpropyl] amino]-10-oxooctahydro-6Hpyridazino[1,2-][1,2] diazepine-1-carboxylic acid} is
not greater than the area of the principal peak from the
standard solution (1) (0.5%); the area of any peak corresponding to cilazapril hydrate related substance III
{ethyl(1S,9S)-9-[[(S)-1-(ethoxycarbonyl)-3phenylpropyl]
amino]-10-oxooctahydro-6Hpyridazino[1,2-][1,2] diazepine-1-carboxylate} is not
greater than 0.2 times the area of the principal peak from

the standard solution (1) (0.1%); the area of any peak,
apart from the principal peak and the peaks corresponding to the related substances II, III and IV, is not greater
than 0.2 times the area of the principal peak from the
standard solution (1) (0.1%); and the sum of the areas of
all the peaks, apart from the principal peak, is not greater
than twice the area of the principal peak from the standard solution (1) (1%). Disregard any peak with an area
less than 0.1 times that of the principal peak from the
standard solution (1) and any peak due to the related substance I.
Mobile phase: Mix 10 mL of triethylamine and 750
mL of water, adjust to pH 2.30 with phosphoric acid, and
add 200 mL of tetrahydrofuran.
System suitability
Test for required detectability: Perform the test with
(1) according to the above operating conditions. The retention times relative to cilazapril are about 0.6 for the
related substance II, 0.9 for the related substance IV, and
1.6 for the related substance III.
System performance: Perform the test with 20 L
each of the standard solutions (1) and (2) according to
the above operating conditions. Adjust the sensitivity of
the system so that the height of the principal peak from
the standard solution (1) is at least 50% of the full scale
of the recorder. The test is valid when the resolution between the peaks of cilazapril and the related substance IV
from the standard solution (2) is at least 2.5.
Time span of measurement: 2 times as long as the retention time of cilazapril. When the related substance I
with a relative retention time of 4 to 5 is present, the
chromatography should be continued until it is eluted.
Water Between 3.5% and 5.0% (0.30 g, volumetric titration, direct titration).
Assay Dissolve 0.30 g of Cilazapril Hydrate, accurately weighed, in 10 mL of ethanol and add 50 mL of water,
and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 41.75 mg of C22H31N3O5
Cimetidine
HN
N
NCN
H3C
CH2SCH2CH2NH
NHCH3
C10H16N6S: 252.34
Cimetidine, when dried, contains not less than 99.0% and
not more than 101.0% of cimetidine (C10H16N6S).
Description Cimetidine is a white crystalline powder,
Cimetidine is freely soluble in methanol or in glacial
acetic acid, sparingly soluble in ethanol, slightly soluble
in water and practically insoluble in ether.
Cimetidine dissolves in dilute hydrochloric acid.
Cimetidine is gradually colored by light.
Identification (1) To 0.1 mL of a solution of Cimetidine in ethanol (1 in 100), add 5 mL of citric acid-acetic
anhydride TS and heat in a water bath for 15 minutes: a
red-purple color develops.
(2) Determine the infrared spectra of Cimetidine and
Cimetidins RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
pH Dissolve 0.5 g of Cimetidine in 50 mL of freshly
boiled and cooled water, shake for 5 minutes and filter:
the pH of the filtrate is between 9.0 and 10.5.
Melting Point

g of Cimetidine in 10 mL of methanol: the solution is
clear and colorless to pale yellow in color.
(2) Heavy metalsProceed with 2.0 g of Cimetidine
(3) ArsenicDissolve 1.0 g of Cimetidine in 5 mL
of dilute hydrochloric acid and perform the test with this
(4) Related substancesDissolve 0.5 g of Cimetidine in 10 mL of methanol and use this solution as the
test solution. Pipet exactly 1 mL of the test solution, add
methanol to make exactly 100 mL and pipet exactly 1
mL of this solution, add methanol to make exactly 10 mL
the test with these solutions as directed under the Thinlayer Chromatography. Spot 4 L each of the test solution and the standard solution on a plate of silica gel for
thin-layer chromatography. Develop the plate with the
mixture of ethyl acetate, methanol and strong ammonia
KP 9 217
water (21 : 2 : 2) to a distance of about 15 cm, air-dry the
plate and then dry at 80 C for 30 minutes. Allow the
plate to stand in iodine vapor for 45 minutes: any spot
other than the principal spot from the test solution is not
hours).
Assay Weigh accurately about 0.24 g of Cimetidine,
previous dried, dissolve in 75 mL of glacial acetic acid

= 25.234 mg of C10H16N6S
Cimetidine Tablets
Cimetidine Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of cimetidine
(C10H16N6S: 252.34).
Method of Preparation Prepare as directed under Tablets, with Cimetidine.
Identification The retention time of the major peak in
the chromatogram of the Assay preparation corresponds
to that of the standard preparation as obtained in the Assay.
Dissolution Test Perform the test with 1 tablet of Cimetidine Tablets at 100 revolutions per minute according
to Method 1 under Dissolution Test, using 900 mL of
0.01 mol/L hydrochloric acid as a dissolution solution.
Take the dissolved solution 15 minutes after start of the
test and make any necessary dilute in 0.01 mol/L hydrochloric acid and use this solution as the test solution.
Separately, weigh accurately sufficient quantity of Cimetidine RS and dissolve in 0.01 mol/L hydrochloric acid
and make the same concentration as the test solution and
absorbances of the test solution and standard solution at
the maximum absorption wavelength of about 218 nm as
directed under the Ultraviolet-visible Spectrophotometry,
using 0.01 mol/L hydrochloric acid as the blank.
The dissolution rate of Cimetidine Tablets in 15 minutes
is not less than 80%.

Cimetidine Tablets. Weigh accurately a portion of the
powder, equivalent to 0.1 g of cimetidine (C10H16N6S),
add 50 mL of methanol, shake, mix for 2 minutes, then
add 40 mL of water, ultrasonicate, mix for 15 minutes
and add water to make exactly 250 mL. Pipet 5 mL of
this solution and add mobile phase to make exactly 200
weigh accurately 20 mg of Cimetidine RS, dissolve in a
mixture of water and methanol (4 : 1) to make exactly 50
mL, pipet 5 mL of this solution and add mobile phase to
make exactly 200 mL and use this solution as the standard solution. Perform the test with 50 mL each of the
test solution and standard solution as directed under the
Liquid Chromatography according to the following conditions and calculate the ratios, AT and AS , of the
peak area of Cimetidine, for the test solution and the
Amount (mg) of cimetidine (C10H16N6S)

= amount(mg) of Cimetidine RS
AT
AS
Mobile phase: To 200 mL of methanol, add 0.3 mL of
phosphoric acid , add water to make 1000 mL and mix.
above operating conditions, relative standard deviation of
the peak areas is not more than 2.0%.
Cimetidine Hydrochloride
HN
HCl
NCN
H3C
CH2SCH2CH2NH
NHCH3
C10H16N6SHCl : 288.80
Cimetidine Hydrochloride contains not less than 98.0%
and not more than 102.0% of cimetidine hydrochloride
(C10H16N6SHCl), calculated on the dried basis
.

Description Cimetidine Hydrochloride is a white crystalline powder.
Cimetidine Hydrochloride is freely soluble in water, and
sparingly soluble in ethanol.
Identification (1) Dissolve about 15 mg, accurately
weighed, of Cimetidine Hydrochloride and Cimetidine
Hydrochloride RS, respectively, in 0.05 mol/L sulfuric
acid TS to exactly 100 mL. Pipet 5.0 mL each of the solutions, add 0.05 mol/L sulfuric acid TS to make exactly
50 mL and use these solutions as the test solution and the
standard solution, respectively. Determine the absorption
spectra of the test and standard solutions, respectively, as
directed under Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Cimetidine Hydrochloride and Cimetidine Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry, respectively:
Purity (1) Heavy metalsProceed with 1.0 g of Cimetidine Hydrochloride according to Method 2 and perform
(2) Related substancesWeigh accurately about 0.1
g of Cimetidine Hydrochloride, add mobile phase to
make exactly 250 mL, and use this solution as the test
solution. Pipet exactly 1.0 mL of the test solution, add
mobile phase to make exactly 500 mL, and use this solution as the standard solution. Perform the test with exactly 50 L each of the test and the standard solutions as directed under Liquid Chromatography according to the
following conditions. Determine each peak area by the
automatic integration method and calculate the percentage of each related substance: Each related substance
is not greater than 0.2%, and the sum of all related substances is not more than 1.0%.
Amount (%) of each related substance = 0 . 2
Ai
AS
Ai : the peak area of each related substance in the

chromatogram obtained from the test solution
AS : the peak area of cimetidine in the chromatogram
obtained from the standard solution
Mobile phase: Dissolve 0.94 g of sodium 1hexanesulfonate in 240 mL of methanol, and add 0.3 mL
of phosphoric acid and water to make 1000 mL.

System suitability
System performance: Dissolve 50 mg of Cimetidine Hydrochloride in 100 mL of 1 mol/L hydrochloric
acid TS and heat on a steam bath for about 10 minutes
and cool. Pipet 1.0 mL of this solution and add mobile
phase to make 250 mL. When the procedure is run with
50 L of this solution under the above operating condition, the resolution between the peaks of cimetidine and
its amide analog is not less than 4.0. And when the procedure is run with 50 L of the standard solution under
the above operating condition, the capacity factor is not
less than 3.0 and the number of theoretical plates is not
less than 2000.
above operating conditions, the relative standard deviation of the peak area of cimetidine is not more than 7.0%.
hours).
Assay Weigh accurately about 0.115 g of Cimetidine
Hydrochloride, add 50 mL of water to dissolve, add 50
mL of methanol and water to make exactly 250 mL. Pipet 5.0 mL of this solution, add mobile phase to make
exactly 200 mL, and use this solution as the test solution.
Separately, weigh accurately about 50 mg of Cimetidine
Hydrochloride RS, add a mixture of water and methanol
(80 : 20) to make exactly 100 mL. Pipet 5.0 mL of this
solution, add mobile phase to make exactly 200 mL, and
use this solutions the standard solution. Perform the test
with exactly 50 L each of the test solution and the standard solution as directed under Liquid Chromatography
peak area of cimetidine, AT and AS , respectively.
Amount (mg) of Cimetidine Hydrochloride

(C10H16N6SHCl)
= Cimetidine Hydrochloride RS (mg)
AT
2 .5
AS
Mobile phase: To 200 mL of methanol add 0.3 mL of
phosphoric acid and water to make 1000 mL.
Flow rate: about 2 mL/minute
System suitability
with 50 L of the standard solution under the above op-
KP 9 219
erating condition, the number of theoretical plates is not
less than 1000 and capacity factor is not less than 0.6.
above operating conditions, the relative standard deviation of the peak area of cimetidine is not more than 2.0%.

tight containers.
Cinnarizine
H
N
N
C26H28N2 : 368.51
Cinnarizine contains not less than 99.0% and not more
than 101.0% of cinnarizine (C26H28N2), calculated on the
dried basis.
Description Cinnarizine is a white powder.
Cinnarizine is freely soluble in methylene chloride, soluble in acetone, slightly soluble in ethanol or in methanol, and practically insoluble in water.
Identification (1) Dissolve 0.2 g of anhydrous citric
acid in 10 mL of acetic anhydride in a water-bath at
80 C and maintain the temperature for 10 minutes. Add
about 20 mg of Cinnarizine. A purple color develops.
(2) Determine the infrared absorption spectra of Cinnarizine and Cinnarizine RS as directed in the potassium
(3) Dissolve 10 mg of Cinnarizine in methanol to
Separately, dissolve 10 mg of Cinnarizine RS in methanol to make 5 mL, and use this solution as the standard
solution (1). Dissolve 10 mg of Cinnarizine RS and 10
mg of Flunarizine Dihydrochloride RS in methanol and
dilute to 20 mL with methanol. Use the solution as the
standard solution (2). Perform the test with these solutions as directed under the Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solutions on a plate of silica gel with fluorescent indicator for
thin-layer chromatography, develop with a mixture of
acetone, methanol and 1 mol/L sodium chloride solution
(50:30:20) to a distance of about 15 cm, and dry the plate
in air. Examine in ultraviolet light at 254 nm, and compare the principal spot from the test solution with that
from the standard solution (1). Their Rf values are the
same. This test is valid when the chromatogram from the

standard solution (2) shows two clearly separated spots.
g of Cinnarizine in methylene chloride to make 20 mL.
The solution is clear and has no more color than the following control solution.
Control solutionTo a mixture of 24 mL of Ferric

Cholride Calorimetric Stock Solution, 10 mL of Cobaltous Chloride Colorimetric Stock Solution and 4 mL of
Cupric Sulfate Colorimetric Stock Solution add 62 mL of
1 w/w% hydrochloric acid and mix. To 2.5 mL of this
solution add 97.5 mL of 1 w/w% hydrochloric acid and
mix.
(2) Acidity or alkalinitySuspend 0.5 g of Cinnarizine in 15 mL of water. Boil for 2 minutes, cool, and filter. Dilute the filtrate to 20 mL with water, and use this
solution as the test solution. To 10 mL of the test solution, add two drops of phenolphthalein TS and 0.25 mL
of 0.01 mol/L sodium hydroxide. The solution is pink.
When two drops of methyl red TS and 0.25 mL of 0.01
mol/L hydrochloric acid are added to 10 mL of the test
solution, the solution is red.
(3) Heavy metals Dissolve 1.0 g of Cinnarizine in
a mixture of acetone and water (85:15). Add dilute hydrochloric acid until dissolution is complete. Dilute to 20
mL with a mixture of acetone and water (85:15), and use
this solution as the test solution. To 12 mL of the test solution, add 2 mL of sodium acetate buffer solution (pH
3.5), and mix with 1.2 mL of thioacetamide. Allow to
stand still for 2 minutes. Mix 10 mL of diluted lead standard solution with 2 mL of the test solution, proceed in
the same manner as above, and use this solution as the
standard solution. The color obtained with the test solution is not more intense than that observed with the standard solution (not more than 20 ppm).
(4) Related substancesDissolve 25.0 mg of Cinnarizine in methanol to make exactly 100 mL, and use this
solution as the test solution. Separately, dissolve 12.5 mg
of Cinnarizine RS and 15.0 mg of Flunarizine Dihydrochloride RS in methanol to make 100 mL. Dilute 1.0
mL of this solution to 20 mL with methanol, and use the
solution as the standard solution (1). Dilute 1.0 mL of the
test solution to 100 mL with methanol. Dilute 5.0 mL of
this solution to 20 mL with methanol, and use this solution as the standard solution (2). Perform the test with 10
L each of methanol (as a blank), the test solution and
the standard solutions as directed under the Liquid
Chromatography according to the following conditions.
In the chromatogram of the test solution, the area of any
peak, other than the principal peak, is not greater than the
area of the principal peak from the standard solution (2)
(0.25%); and the sum of the areas of the peaks, other
than the principal peak, is not greater than twice the area
of the principal peak from the standard solution (2)

(0.5%). Disregard any peak due to the blank and any
peak with an area less than 0.2 times the area of the principal peak from the standard solution (2).
Column: A stainless steel column about 4.0 mm inside diameter and 10 cm in length, packed with basedeactivated octadecylsilanized silica gel for liquid chromatography (3 m in particle diameter).
Mobile phase: Variable mixtures of mobile A and
mobile phase B, and program the chromatograph as follows.
Mobile phase A: 1 w/v% ammonium acetate solution
Mobile phase B: 0.2 v/v% solution of glacial acetic
acid in acetonitrile
Time
(min)
0 ~ 20
20 ~ 25
Mobile
phase A (%)
75 10
10
25 ~ 30 75
30 = 0
75
Mobile
Elution
phase B (%)
25 90
linear gradient
90
isocratic
switch to initial
25
eluent composition
25
restart gradient

System suitability
system so that the height of the principal peak is at least
50% of the full scale of the recorder. When the procedure
is run with the standard solution (1) under the above operating conditions, the retention times are about 11 minutes for cinnarizine and about 11.5 minutes for flunarizine. The test is valid when the resolution of these peaks
between cinnarizine and flunarizine is at least 5.0. If necessary, adjust the time programm for the gradient elution.
Loss on Drying Not more than 0.5% (1 g, vacuum, 60
C, 4 hours).
Assay Dissolve 0.15 g of Cinnarizine, accurately
weighed, in 50 mL of a mixture of ethyl methyl ketone
and glacial acetic acid (7 : 1), and titrate with 0.1 mol/L
perchloric acid VS (indicator: 4 drops of naphtholbenzein TS). Perform a blank determination and make any necessary correction.

= 18.426 mg of C26H28N2.
Ciprofloxacin Hydrochloride
Hydrate
HN
N
HCl
H2O
OH
F
O
C17H18FN3O3HClH2O: 385.82
Ciprofloxacin Hydrochloride Hydrate contains not less
than 98.0% and not more than 102.0% of ciprofloxacin
hydrochloride (C17H18FN3O3HCl), calculated on the anhydrous basis.
Description Ciprofloxacin Hydrochloride Hydrate is a
pale yellow, crystalline powder.
Ciprofloxacin Hydrochloride Hydrate is sparingly soluble in water, slightly soluble in acetic acid or methanol,
very slightly soluble in dehydrated ethanol, and practically insoluble in acetone, acetonitrile, ethyl acetate,
hexane or dichloromethane.
Ciprofloxacin Hydrochloride Hydrate and Ciprofloxacin
Hydrochloride Hydrate RS, previously dried, as directed
(2) Dissolve 0.1 g of Ciprofloxacin Hydrochloride
Hydrate in water to make 10 mL and use this solution as
the test solution. Separately, dissolve 0.1 g of Ciprofloxacin Hydrochloride Hydrate RS in 10 mL of water and
each of the test and the standard solution on a plate of silica gel for thin-layer chromatography. Allow the plate to
stand in the container with ammonia gas for 15 minutes.
Develop the plate with a mixture of dichloromethane,
methanol, strong ammonia water and acetonitrile (4 : 4 :
nm and 365 nm): the spot from the test solution exhibits
similar intensity and same Rf value as the spot from the
standard solution.
(3) A solution of Ciprofloxacin Hydrochloride Hydrate (1 in 50) responds to the Qualitative Tests for chloride.
pH Dissolve 1.0 g of Ciprofloxacin Hydroxide Hydrate
in 40 mL of freshly boiled and cooled water: the pH of
KP 9 221
Purity (1) Heavy metalsProceed with 1.0 g of Ciprofloxacin Hydrochloride Hydrate according to Method
2 and perform the test. Prepare the control solution with
(2) SulfatePerform the test with 0.375 g of Ciprofloxacin Hydrochloride Hydrate. Prepare the control solution with 0.30 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.04%).
(3) Fluoroquinolonic acidWeigh a suitable
amount of Ciprofloxacin Hydrochloride Hydrate, dissolve in water to make a solution containing 10 mg per
weigh accurately about 5.0 mg of Fluoroquinolonic Acid
RS, add 50 L of ammonia TS and water to make 50 mL.
Pipet 2.0 mL of this solution, add water to make 10 mL
the test according to Thin-layer Chromatography with
the test solution and the standard solution. Spot 5 L
each of the test and the standard solution on a plate with
silica gel for thin-layer chromatography. Allow the plate
to stand in the container with 50 mL of ammonia TS for
15 minutes. Develop the plate with a mixture of dichloromethane, methanol, strong ammonia water and acetonitrile (4 : 4 : 2 : 1) to a distance of about 15 cm and airdry the plate for 15 minutes. Examine under the ultraviolet light (main wavelength: 250 nm): Rf value corresponding to the principal spot from the standard solution,
the spots other than the principal spot from the test solution are not larger or not more intense than the spot from
the standard solution (not more than 0.2%).
(4) Related substancesPerform the test according
to the operating conditions in the Assay. Determine each
peak area of impurities, Ai , from the test solution and
the total area of all peaks, AT and calculate the content

of each peak area of impurities according to the following equation.
Amount (%) of each of impurities = 100
Ai
AS
Each derivative of ciprofloxacin ethylenediamine and related substance is not more than 0.2% and the total of all
related substances is not more than 0.5%.
Assay Weigh accurately about 25 mg of Ciprofloxacin
Hydrochloride Hydrate, dissolve in mobile phase to
make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately a suitable amount of
Ciprofloxacin Hydrochloride Hydrate RS (determined
formerly water contents as directed under water determination assay), dissolve in mobile phase to make a solu-
tion containing about 0.5 mg per mL and use this solution as the standard solution. Perform the test with 10 L
each of the test and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and determine the peak area of
ciprofloxacin hydrochloride, AT and AS , of the test
Amount (mg) of ciprofloxacin hydrochloride
(C17H18FN3O3HCl) = 50 C
AT
AS
C: the concentration of Ciprofloxacin Hydrochloride

Hydrate RS in the standard solution, calculated on the
anhydrous basis (mg/mL).
Column Temperature: A constant temperature of
about 30 C.
Mobile phase: A mixture of 0.025 mol/L phosphoric
acid adjusted to pH 3.0 0.1 with triethylamine and acetonitrile (87 : 13).
System suitability
System performance: Dissolve Ciprofloxacin
Ethylenediamine derivative RS in the standard solution
of ciprofloxacin to make a solution containing 0.5 mg
per mL. Perform the test with 10 L of this solution according to the above operating conditions. Ciprofloxacin
ethylenediamine derivative and ciprofloxacin are eluted
in this order and the resolution between ciprofloxacin
ethylenediamine derivate and ciprofloxacin are not less
than 6.
above operating conditions, relative standard derivation
of the peak area of ciprofloxacin is no more than 1.5%.
Ciprofloxacin Hydrochloride
Tablets
Ciprofloxacin Hydrochloride Tablets contain not less
amount of ciprofloxacin (C17H18FN3O3 : 331.34).
Method of Preparation Prepare as directed under tab-

lets, with Ciprofloxacin Hydrochloride Hydrate.
Identification (1) The retention time of the major peak
in the chromatography of the test solution corresponds to
that of the standard solution obtained as directed in the
Assay.
(2) Place a number of tablets, equivalent to 1.5 g of
ciprofloxacin, in a suitable flask containing 750 mL of
water and sonicate for about 20 minutes. Dilute with water to 1000 mL and centrifuge a portion of this suspension and use the supernatant solution obtained as the test
solution. Separately, dissolve a suitable quantity of Ciprofloxacin Hydrochloride Hydrate RS in water to obtain
a solution containing 1.5 mg per mL and use this solution
for thin-layer chromatography. Allow the plate to stand
in the container with ammonia gas for 15 minutes. Develop the plate with a mixture of dichloromethane, methanol, ammonia TS and acetonitrile (4 : 4 : 2 : 1) to a
distance of about 15 cm. Remove the plate and allow it
to air-dry for about 15 minutes. Examine under ultraviolet light (main wavelength: 254 nm and 366 nm): the
principal spot from the test solution exhibits the same
Rf value as the principal spot from the standard solution.

according to the operating conditions of the Assay of Ciprofloxacin Hydrochloride Hydrate and determine the
peak areas, AT and AS , of ciprofloxacin for the test
Amount (mg) of ciprofloxacin (C17H18FN3O3) =
C
L AT 331 .34
D A S 367 .81
C : Concentration of ciprofloxacin hydrochloride in

the standard solution, calculated on the anhydrous basis
(mg/mL).
L : Labeled amount of ciprofloxacin in each tablet
(mg).
D : Concentration of Ciprofloxacin Hydrochloride in
the test solution (mg/mL).
Cisplatin
Cl
Cl
Dissolution Test Perform the test with 1 tablet of Ciprofloxacin Hydrochloride Tablets at 50 revolutions per
using 900 mL of 0.01 mol/L hydrochloric acid as a dissolution medium. 30 minutes later after starting the test,
take the dissolution medium and filter. If necessary,
make a test solution by diluting with the dissolution medium. Separately weigh accurately a portion of ciprofloxacin hydrochloride hydrate and dissolve in the dissolution medium to the same concentration with the test solution and use this solution as the standard solution. Determine the absorbances of the test solution and the standard solution at 276 nm as directed under the Ultravioletvisible Spectrophotometry, using the dissolution medium
as a blank. The dissolution rate of ciprofloxacin hydrochloride in 30 minutes is not less than 80%.
Assay Transfer 5 tablets in 400 mL of water and sonicate for about 20 minutes. Dilute with water to make exactly 500 mL. Dilute an accurately measured volume of
this solution with water to obtain a solution containing
the equivalent of the labeled amount of ciprofloxacin
(C17H18FN3O3) about 0.3 mg per mL and use this solution as the test solution. Separately dissolve a suitable
amount, accurately weighed, of Ciprofloxacin Hydrochloride Hydrate RS (formerly determined water contents
as directed under water determination assay) in water to
obtain a solution containing about 0.3 mg per mL and
NH3
Pt
NH3
Cl2H6N2Pt : 300.05
Cisplatin, when dried, contains not less than 98.0% and
not more than 102.0% of cisplatin (Cl2H6N2Pt).
Description Cisplatin is a yellow crystalline powder.
Identification (1) Add 2 to 3 drops of stannous chloride dihydrate solution (1 in 100) to 5 mL of a solution of
Cisplatin in water (1 in 2000): brown precipitate forms.
of Cisplatin and Cisplatin RS, respectively, in a solution
of sodium chloride (9 in 1000) in 0.01 mol/L hydrochloric acid TS (1 in 2000) as directed under Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(3) Determine the infrared spectra of Cisplatin and
Cisplatin RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) TrichloroammineplatinatePerform this
procedure without exposure of daylight, using lightresistant ressels. Weigh 50 mg of Cisplatin, and add a solution of sodium chloride (9 in 1000) to make exactly
100 mL and use this solution as the test solution. Separately, weigh 10 mg of Trichloroammineplatinate RS,
previously dried at 80 C for 3 hours, add a solution of
KP 9 223
sodium chloride (3 in 1000) to make exactly 200 mL. Pipet 2.0 mL of this solution, add a solution of sodium
chloride (9 in 1000) to make exactly 20 mL and use this
exactly 40 L each of the test solution and the standard
solution as directed under Liquid Chromatography according to the following conditions, and determine each
peak area by the automatic integration method: the peak
area trichloroammineplatinate from the test solution is
not larger than the peak area from the standard solution.
quartanaryammonium group introduced octadecylsilanized silica gel for Liquid Chromatography (10 m in
particle diameter).
about 25 C.
Mobile phase: A solution of ammonium sulfate (1 in
800)
time of trichloroammineplatinate is about 8 minutes.
System suitability
with 40 L of the standard solution under the above operating condition, the number of theoretical plates and
the symmetry factor of the peak of trichloroammineplatinate are not less than 1500 and not more than 2.0, respectively.
above operating conditions, the relative standard deviation of the peak area of trichloroammineplatinate is not
more than 3.0%.
hours).
Assay Perform this procedure without exposure of daylight, using light-resistant ressels. Weigh accurately
about 25 mg each of Cisplatin and Cisplatin RS, previously dried, add dimethylformamide to make exactly
standard solution, respectively. Perform the test with exactly 40 L each of the test solution and the standard solution as directed under Liquid Chromatography according to the following conditions, and determine peak area
of cisplatin, AT and AS , by the automatic integration
method, respectively.
Amount (mg) of cisplation (Cl2H6N2Pt)

= amount (mg) of Cisplation RS AT
AS

diameter and 25 cm in length, packed with aminopropylsilyl silica gel for Liquid Chromatography (5 m in particle diameter).
about 25 C.
Mobile phase: A mixture solution of ethyl acetate, methanol, water and dimethylformamide (25 : 16 : 5 : 5)
time of cisplatin is about 4 minutes.
System suitability
with 40 L of the standard solution under the above operating condition, the number of theoretical plates and
the symmetry factor of the peak of cisplatin are not less
than 3000 and not more than 2.0, respectively.
above operating conditions, the relative standard deviation of the peak area of cisplatin is not more than 1.0%.
Citric Acid Hydrate

CH2CO2H
HO
CO2H
H2O
CH2CO2H
C6H8O7H2O: 210.14
Citric Acid Hydrate contains not less than 99.5% and not
more than 100.5% of anhydrous citric acid (C6H8O7 :
Description Citric Acid Hydrate is a colorless crystal,
white granule or crystalline powder, is odorless and has a
strong acid taste.
Citric Acid Hydrate is very soluble in water, and freely
soluble in ethanol
Citric Acid Hydrate is efflorescent in dry air.
Identification Determine the infrared spectra of Citric
Acid Hydrate and Citric Acid Hydrate RS, previously
dried at 105 C for 2 hours, as directed in the potassium
bromide disk method under Infrared Spectrophotometry:
both spectra similar intensities of absorption at the same
wave numbers.
g of Citric Acid Hydrate in water to make 10 mL: the solution is clear and has no more color than the following
control solutions (1), (2), or (3).
Control solution (1): To 1.5 mL of cobalt (II) chloride colorimetric stock solution and 6.0 mL of iron (III) chloride
colorimetric stock solution add water to make 1000 mL.

Control solution (2): To 0.15 mL of cobalt (II) chloride
colorimetric stock solution, 7.2 mL of iron (III) chloride
colorimetric stock solution and 0.15 mL of copper (II)
sulfate colorimetric stock solution add water to make
1000 mL.
Control solution (3): To 2.5 mL of cobalt (II) chloride colorimetric stock solution, 6.0 mL of iron (III) chloride
colorimetric stock solution and 1.0 mL of copper (II) sulfate colorimetric stock solution add water to make 1000
mL.
(2) SulfatesDissolve 2.0 g of Citric Acid Hydrate
in water to make 30 mL, and use this solution as the test
solution. Separately, dissolve 0.181 g of potassium sulfate in diluted dehydrated ethanol (3 in 10) to make exactly 500 mL. Pipet exactly 5 mL of this solution, and
add diluted dehydrated ethanol (3 in 10) to make exactly
100 mL. To 4.5 mL of this solution add 3 mL of a solution of barium chloride dihydrate (1 in 4), shake, and allow to stand for 1 minute. To 2.5 mL of this solution add
15 mL of the test solution and 0.5 mL of acetic acid, and
allow to stand for 5 minutes: the solution has no more
turbidity than the following control solution.
Control solutionDissolve 0.180 g of potassium sulfate in water to make exactly 500 mL. Pipet exactly 5 mL
of this solution and add water to make exactly 100 mL.
(3) Oxalic acidDissolve 0.80 g of Citric Acid Hydrate in 4 mL of water, add 3 mL of hydrochloric acid
and 1 g of zinc, and boil for 1 minute. After allowing to
stand for 2 minutes, take the supernatant liquid, add 0.25
mL of a solution of phenyl hydrazinium hydrochloride (1
in 100), heat to boil, and then cool quickly. To this solution add the equal volume of hydrochloric acid and 0.25
mL of a solution of potassium hexacyanoferrate (III) (1
in 20), mix, and allow to stand for 30 minutes: the solution has no more color than the following control solution prepared at the same time.
Control solutionTo 4 mL of a solution of oxalic acid dihydrate (1 in 10000) add 3 mL of hydrochloric acid
and 1 g of zinc.
(4) Heavy metalsProceed with 2.0 g of Citric Acid
test with 0.5 g of Citric Acid Hydrate, provided that the
solution is heated at 90 C for 1 hour and then cool
quickly: the solution has no more color than Matching
Fluid K.
Assay Weigh accurately about 1.5 g of Citric Acid Hy-
drate, dissolve in 50 mL of water and titrate with 1 mol/L

= 64.04 mg of C6H8O7
Anhydrous Citric Acid

CH2CO2H
HO
CO2H
CH2CO2H
C6H8O7: 192.12
Anhydrous Citric Acid contains not less than 99.5% and
not more than 101.0% of anhydrous citric acid (C6H8O7),
Description Anhydrous Citric Acid is a colorless crystal, white granule or crystalline powder.
Anhydrous Citric Acid is very soluble in water, and freely soluble in ethanol.
under Citric Acid Hydrate.
Purity Proceed as directed in the Purity under Citric
Acid Hydrate.
direct titration).
Assay Weigh accurately about 0.55 g of Anhydrous Citric Acid, dissolve in 50 mL of water, and titrate with 1
mol/ L sodium hydroxide VS (indicator: 2 drops of phenolphthalein TS).

= 64.04 mg of C6H8O7
KP 9 225
ter to make 20 mL, and use this solution as the test solution. The pH of the solution is between 8.0 and 10.0.
Clarithromycin
Purity Heavy metalsProceed with 2.0 g of Clarithromycin according to Method 4 and perform the test.
O
H3C
CH3
O
HO
OH
H3C
CH3
OH
CH3
CH3
H3C
O
O
H3C
CH3

direct titration).
O
H3C
CH3
O
O
CH3
Residue on Ignition Not more than 0.1 % (2.0 g).
O
CH3
OH
CH3
C38H69NO13: 747.95
Clarithromycin is a derivative of erythromycin.
Clarithromycin contains not less than 900 g (potency)
per mg of clarithromycin (C38H69NO13), calculated on the
anhydrous basis.
Description Clarithromycin is a white crystalline
powder, is odorless, and has a bitter taste.
Clarithromycin is soluble in acetone or in chloroform,
slightly soluble in methanol, in ethanol, or in ether, and
Identification (1) To 5 mg of Clarithromycin add 2 mL
of sulfuric acid, and mix with shaking: the red-brown
color develops.
(2) To 3 mg of Clarithromycin, add 2 mL of acetone,
and add 2 mL of hydrochloric acid: the orange color develops and the color turns immediately to red to dark
purple.
(3) Dissolve Clarithromycin in chloroform to make a
solution so that each mL contains about 2.5 mg, and use
this solution as the test solution. Separately, dissolve Clarithromycin RS in chloroform to make a solution so that
each mL contains about 2.5 mg, and use this solution as
the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot
5 L of the test solution and the standard solution on a
plate of silica gel for thin-layer chromatography. Develop the plate with the mixture of chloroform, methanol
and strong ammonia water (100 : 5 : 1), air-dry the plate.
Spray evenly sulfuric acid on the plate and heat the plate
at 105 C for 10 minutes. The spots obtained from the
test solution and the standard solution are the same in the
Rf value.
D : -81 ~ -97 (0.25 g
calculated on the anhydrous basis, chloroform, 25 mL,
100 mm).
pH Weigh 50 mg of Clarithromycin, dissolve in 20 mL
of methanol, and take 10 mL of this solution and add wa-

Clarithromycin and Clarithromycin RS, and dissolve
each in the mobile phase to make exactly 20 mL. Pipet
exactly 2 mL each of these solutions, add 2.0 mL of the
internal standard solution, add the mobile phase to make
according to the following operating conditions, and calculate the ratios, QT and QS, of the peak area of clarithromycin to that of the internal standard.
Amount [g (potency)] of clarithromycin (C38H69NO13)

= Amount [g (potency)] of Clarithromycin RS
QT
QS
Internal standard solutionA solution of butyl parahydroxybenzoate in the mobile phase (1 in 20000)
50 C
Mobile phase: A mixture of 0.06 mol/L potassium dihydrogenphosphate solution and acetonitrile (13:7)
time of clarithromycin is about 8 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, clarithromycin and the internal standard are eluted in this order with the resolution between
above operating conditions, the relative standard deviation of the ratios of the peak area of clarithromycin to
that of the internal standard is not more than 2.0 %.

Clebopride Malate
O
HO
CO2H
Cl
N
H
H
HO2C
H2N
the chromatogram obtained with standard solution (2)

according to the above operation condition, shows two
clearly separated bands.
-naphthol solutionDissolve 5g of -naphthol in
40 mL of 2 mol/L sodium hydroxide TS, add water to
make 100 mL.
OCH3
and enantiomer
C20H24ClN3O2C4H6O5 : 507.96
Clebopride Malate, when dried, containes not less than
98.5% and not more than 101.0% of clebopride malate
(C20H24ClN3O2C4H6O5).
Description Clebopride Malate is a white, crystalline
powder.
Clebopride Malate is sparingly soluble in methanol or in
water, slightly soluble in ethanol and practically insoluble in dichloromethane.
Identification (1) Dissolve 20 mg of Clebopride Malate in 1 mL of surfuric acid, add 1 mL of -naphthol TS,
mix and observe under daylight ; The solution shows a
yellow color with blue fluorescence.
(2) Dissolve 20 mg each of Clebopride Malate and
Clebopride Malate RS in water to make 100 mL, add water to 10 mL each of these solutions to make 100 mL and
use these solutions as test solution and standard solution
respactively. Determine the absorption spectra of these
solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
(3) Determine the infrared spectra of Clebopride Malate and Clebopride Malate RS as directed in the potassium bromide disk method under the infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(4) Dissolve 5 mg of Clebopride Malate in ethanol to
make 10 mL and use this solution as the test solution.
Separately, dissolve 5 mg of Clebopride Malate RS in
ethanol to make 10 mL and use this solution as the standard solution (1). Dissolve 5 mg of Clebopride Malate
RS and 5 mg of metoclopramide hydrochloride RS in
ethanol to make 10 mL and use this solution as the standard solution (2). Perform the test with these solutions as
L each of test solution and standard solution as bands of
10 mm on a plate of siliga gel with a fluorescent indicator for thin-layer chromatography. Develop the plates
with a mixture of toluene, methanol, acetone and concentrated ammonia TS (70 : 14 : 14 : 2) to a distance of
about 15 cm and air-dry the plate and examine under ultraviolet light (main wavelength : 254 nm). The main
spot from test solution has the same Rf value as the
spot from standard solution (1). This test is valid when
pH Dissolve 1.0 g of Clebopride Malate in water to

make 100 mL: pH of this solution is between 3.8 and 4.2.
g of Clebopride Malate in water to make 100 mL: this
solution is colorless and clear.
(2) ChlorideDissolve 1.0 g of Clebopride Malate
in 20 mL of glacial acetic acid, add 6 mL of dilute nitric
acid, dilute with water to 50 mL and perform the test.
Prepare the control solution, as follows mix 20 mL of
glacial acetic acid, 6 mL of nitric acid and 0.3 mL of
0.01 mol/L hydrochloric acid VS, and add water to make
50 mL.
(3) SulphatesDissolve 2.0 g of Clebopride Malate
in 20 mL of glacial acetic acid, add water to make 50
mL and perform the test. Prepare the control solution, as
follows mix 20 mL of glacial acetic acid and 0.42 mL of
0.005 mol/L sulfuric acid VS, and add water to make 50
mL (not more than 0.01%).
(4) Heavy metalsProceed with 1.0 g of Clebopride
Malate according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(5) Related substancesDissolve 0.10 g of Clebopride Malate in the mobile phase to make exactly 100
mL and use this solution as the test solution. Add the
mobile phase to 1.0 mL of this solution to make exactly
10 mL and use this solution as the standard solution (1).
Separately, dissolve 10 mg of Clebopride Malate RS and
10 mg of metoclopramide hydrochloride RS in the mobile phase to make exactly 100 mL, add the mobile phase
to 1.0 mL of this solution to make 10 mL and use this solution as the standard solution (2). Perform the test with
20 L each of the test solution and the standard solutions
to the following conditions.
The areas of the peak other than the principal peak from
the test solution and the two peaks eluted within 2 minutes from the test solution are not greater than the area
of the principal peak from standard solution (1) (0.1%);
the sum of the areas of all peaks, other than the principal
peak and two peaks within 2 minutes, is not greater than
3 times the area of the principal peak with standard solution (1) (0.3%). Disregard any peak from an area less
than 0.25 times that of the principal peak with standard
solution (1).
Detector : An ultraviolet-visible absorption photometer (wavelength: 215 nm)
KP 9 227
Column : A stainless steel column, about 4.0 mm in
Column temperature : A room temperature.
Mobile phase : A mixture of sodium heptane sulfonate solution (pH 2.5) and acetonitrile (80 : 20).
Flow rate : 1.0 mL/minute.
System suitability
Perform the test with the standard solution (2) according to the above conditions, adjust the sensitity of
the system so that the heights of the peaks in the chromatogram obtained are at least 30% of the full scale of the
recorder. This test is valid when the retention time of the
second peak (clebopride) is about 15 minutes and the relative retention time to the first peak is about 0.45.
Time span of measurement : About 2 times as long
as the retention time of Clebopride.
Sodium heptane sulfonate solution (pH 2.5) Dissolve 1.0 g of sodium heptane sulfonate in water to make
1000 mL, adjust to pH 2.5 with phosphoric acid.
Loss on Drying not more than 0.5% (1 g, 105 C, constant mass).
Residue on Ignition not more than 0.1% (1 g).
Assay Weigh accurately about 0.4 g of Clebopride Malate, dissolve in 50 mL of glacial acetic acid and titrate
with 0.1 mol/L perchloric acid (potentiometric titration,
1 mL of 0.1 mol/L Perchloric acid

= 50.80 mg of C20H24ClN3O2C4H6O5
well-closed containers..
Clemastine Fumarate
Cl
CH3
Identification (1) To 5 mg of Clemastine Fumarate,

add 5 mL of sulfuric acid and shake to dissolve: a yellow
color is observed. Slowly drop this solution into 10 mL
of water: the yellow color immediately disappears.
(2) To 10 mg of Clemastine Fumarate, add 1 mL of
fuming nitric acid and evaporate on a water-bath to dryness. Then add 2 mL of diluted hydrochloric acid (1 in 2)
and 0.2 g of zinc powder, heat for 10 minutes on a waterbath, cool and filter. Add 20 mL of water to the filtrate.
The solution responds to the Qualitative Tests for primary aromatic amines.
(3) To 5 mL of a solution of Clemastine Fumarate (1
in 50000), add 5 mL of p-dimethyl-aminobenzaldehyde
TS and warm for 10 minutes: a red-purple color is observed.
(4) Perform the test with Clemastine Fumarate as directed under the Flame Coloration Test (2): a green color
is observed.
(5) Dissolve 40 mg of Clemastine Fumarate and 10
mg of fumaric acid in 2 mL each of a mixture of ethanol
and water (4 : 1) by gentle warming and use these solutions as the test solution and the standard solution, respectively. Perform the test with the test solution and the
standard solution as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the
plate with a mixture of isopropyl ether, formic acid and
water (90 : 7 : 3) to a distance of about 10 cm and air-dry
the plate. Examine the plate under ultraviolet light (main
wavelength: 254 nm): the spot with larger Rf value
from the test solution has the same Rf value as the spot
D : Between +16 and
Melting Point
composition).
CH3
N
Description Clemastine Fumarate is a white, crystalline powder and is odorless.

Clemastine Fumarate is sparingly soluble in methanol or
in glacial acetic acid, slightly soluble in ethanol, very
slightly soluble in ether and practically insoluble in water.
HO2C
H
C
C
O
H
Between 176 C and 180 C (with de-
CO2H
C21H26ClNOC4H4O4: 459.96
Clemastine Fumarate, when dried, contains not less than
98.5% and not more than 101.0% of clemastine fumarate
(C21H26ClNOC4H4O4).

0.5 g of Clemastine Fumarate in 10 mL of methanol by
warming: the solution is clear and colorless.
(2) Heavy metalsPerform the test with 1.0 g of
Clemastine Fumarate according to Method 2. Prepare the
Clemastine Fumarate according to Method 3 and perform
(4) Related SubstancesDissolve 0.10 g of Clemastine Fumarate in 5 mL of methanol and use this solution

as the test solution. Pipet 1 mL of the test solution, add
methanol to make exactly 250 mL and use this solution
as the standard solution (1). Pipet 5 mL of this solution,
add methanol to make exactly 10 mL and use this solution as the standard solution (2). Perform the test with the
test solution and the standard solutions (1) and (2) as directed under the Thin-layer Chromatography. Spot 5 L
each of the test solution and the standard solutions (1)
and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
methanol and strong ammonia water (90 : 10 : 1) to a
distance of about 15 cm and air-dry the plate. After
spraying evenly Dragendorffs TS on the plate, immediately spray evenly hydrogen peroxide TS: the spots
other than the principal spot from the test solution are not
more intense than the spot from the standard solution (1)
and not more than 2 spots from the test solution are more
intense than the spot from the standard solution (2).
hours).
Assay Weigh accurately about 0.4 g of Clemastine
Fumarate, previously dried, dissolved in 50 mL of glacial

= 46.00 mg of C21H26ClNOC4H4O4
Clenbuterol Hydrochloride
OH
H
N
Cl
CH3
HCl
CH3
H3C
H2N
Cl
C12H18Cl2N2OHCl : 313.65
Clenbuterol Hydrochloride contains not less than 99.0%
and not more than 101.0% of clenbuterol hydrochloride
(C12H18Cl2N2OHCl), calculated on the anhydrous basis.
Description Clenbuterol Hydrochloride is a white,
crystalline powder.
Clenbuterol Hydrochloride is soluble in water or in
ethanol and slightly soluble in acetone.
Melting pointAbout 173 C (decomposition)

Clenbuterol Hydrochloride and Clenbuterol Hydrochloride RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
(2) Dissolve 10 mg of Clenbuterol Hydrochloride in
10 mL of methanol and use this solution as the test solution. Separately, dissolve 10 mg of Clenbuterol Hydrochloride RS in 10 mL of methanol and use this solution as
fluorescent indicator for thin-layer chromatography. Develop the with a plate mixture of toluene, ethanol and
ammonia TS (15:10:0.15) a distance of about 10 cm, dry
the plate. Splay evenly 1% sodium nitrite solution in 1
mol/L hydrochloric acid, after standing for 10 minutes, dip
the plate in 0.4% naphthylethylenediamine dihydrochloride solution in methanol and remove the plate from the
solution and air-dry the plate: the spots from the test solution and the standard solution show same color and same
Rf -value.
(3) The water solution of Clenbuterol Hydrochloride
(1 in 100) exhibits the Qualitative Reaction (2) of chlorides.
+0.10 (0.30 g, water, 10 mL, 100 mm)
pH Dissolve about 0.5 g of Clenbuterol Hydrochloride
and 7.0.
0.5 g of Clenbuterol Hydrochloride in 10 mL of water:
turbidity of this solution is not more intense than the following control suspension.
Control suspensionDissolve 1.0 g of hydrazine sufate in water to make exactly 100 mL, allow to stand for
between 4 and 6 hours. Add 25.0 mL of this solution to
the solution dissolving 2.5 g of hexamine in water, mix
well, allow to stand for 24 hours. Preserve in glass containers and use within 2 months. When this solution is
used, add water to 15.0 mL of this suspension to make
1000 mL, mix well 90.0 mL of water and 10.0 mL of this
suspension, and use this solution as the control suspension.
(2) Related substancesDissolve 0.1 g of Clenbuterol Hydrochloride in the mobile phase to make exactly
50 mL, use this solution as the test solution. Dilute 0.1
mL of the test solution with water to make 100 mL, use
with 5L each of test solution and the standard solution,
KP 9 229
to the following conditions, measure the peak area of
each solution according to the automatic integration method. The area of any peak other than the principal peak
from the test solution is not greater than the area of the
principal peak from the standard solution (0.1%) and the
sum of the areas of all the peaks other than the principal
peak form the test solution is not greater than 2 times the
area of the principal peak from the standard solution
(0.2%). Disregard any peak with an area less than 0.1
times the area of the principal peak from the standard solution.
Detector: An ultraviolet-visible absorption photometer (wavelength: 215 nm)
Column: A stainless steel column, about 4 mm in inside diameter and about 12.5 cm in length, packed with
(5 m in particle diameter).,
about 40 C.
Mobile phase: A mixture of phosphate buffer solution, methanol and acetonitrile (60 : 20 : 20).
Flow rate : 0.5 mL/minute
System suitability
System performance: Dissolve 10 mg of clenbuterol related substances (1) RS {1-(4-amino-3,5dichlorophenyl)-2-[(1,1-dimethylethyl)amino]ethanol
(cienbuterol-ketone)} with 20 mL of mobile phase, add 5
mL of the test solution, and add mobile phase to make 50
mL. When the procedure is run with 5L of this solution
as directed under the above operating conditions: the
resolution between the related substance peak and
clebuterol peak is not less than 2.5.
Phosphate buffer solutionDissolve sodium decanesulfonate and 5 g of potassium dihydrogen phosphate in
900 mL of water, adjust to pH 3.0 with dilute phosphoric
acid and dilute to 1000 mL with water.
Water Not more than 1.0 % (volumetric titration, direct titration).
Assay Dissolve accurately about 0.25 g in 50 mL of
ethanol and add 5.0 mL of 0.01 mol/L hydrochloric acid.
Titrate with 0.1 mol/L sodium hydroxide. (potentiometric titration Endpoint Detection Method in Titrimetry).
Read the volume added between 1st equivalent point and
2nd equivalent point of inflexion.
1 mL of 0.1 mol/L sodium hydroxide

= 31.365 mg of C12H18Cl2N2OHCl
Clindamycin Hydrochloride
H3C
H
H
N
Cl
CH3
H3C
O
HO
OH
HCl
C18H33ClN2O5SHCl: 461.44
Clindamycin Hydrochloride contains not less than 800
g (potency) of per mg of clindamycin (C18H33ClN2O5S:
Description Clindamycin Hydrochloride is a whtie to
grayish white crystalline powder, and is odorless.
Clindamycin Hydrochloride is freely soluble in water, in
pyridine, or in methanol, slightly soluble in ethanol, and
practically insoluble in acetone or in chloroform.
Clindamycin Hydrochloride and Clindamycin Hydrochloride RS as directed in paste method under Infrared
Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, dissolve each of
Clindamycin Hydrochloride and Clindamycin Hydrochloride RS in an appropriate solvent, evaporate the solvent
to dryness, and repeat the test with the resudes.
(2) Dissolve 50 mg each of Clindamycin Hydrochloride and Clindamycin Hydrochloride RS in 10 mL of methanol, and use these solutions as the test solution and the
directed under Thin-layer Chromatography. Spot 10 L
plate with a mixture of methylethylketone, acetone and
water (8:4:1) to a distance of about 10 cm, and air-dry
the plate. Spray 0.5 % potassium permanganate solution
on the plate, and after 10 minutes spray 0.2 % bromophenol blue solution: The blue spots obtained from the
test solution are the same with the corresponding spots
from the standard solution in the Rf value.
the same as that of the principal peak in the chromatogram obtained with the standard solution.
(4) Clilndamycin Hydrochloride responds to the Qualitative Tests for chloride.
[ ]25
D : +135 ~ +150(0.5 g,

Clindamycin Hydrochloride in 10 mL of water is between 3.0 and 5.5.
Sterility Test It meets the requirement, when Clindamycin Hydrochloride is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Clindamycin Hydrochloride is used in a sterile preparation,.
Weigh an appropriate amount of Clindamycin Hydrochloride, dissolve in Isotonic Sodium Chloride Injecton to
make the solution so that each mL contains 5.0 mg, and
of rabbit.
than 90.0 % and not more than 120 % of the labeled

amount of clindamycin (C18H33ClN2O5S: 424.98).
Mehtod of Preparation Prepare as directed under
Capsules, with Clindamycin Hydrochloride.
Identification (1) Proceed as directed in the Identification (2) under Clindamycin Hydrochloride.

direct titration).

Clindamycin Hydrochloride and Clilndamycin Hydrochloride RS, dissolve in the mobile phase to make exactly
10 L of each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak areas AT and AS, of clindamycin for the
test solution and the standard solution.
Assay Weigh accurately the mass of contents of not

less than 20 Clindamycin Hydrochloride Capsules.
Weigh accurately about 45 mg (potency) according to the
labeled amount, place in a 15 mL stopperd glass centrifuge tube, add 3.0 mL of 1 % sodium carbonate solution
and 3.0 mL of chloroform, centrifuge and discard the
aqueous layer, add 1 g of sodium sulfate anhydrous and
mix with shaking, add 1.0 mL of chloroform, 1.0 mL of
the internal standard solution and 0.6 mL of glacial acetic
acid, close the stopper, and heat at 100 C for 2.5 hours
and cool down, centrifuge, and take the supernatant solution. Use this solution as the test solution. Separetely,
weigh accurately about 45 mg (potency) of Clindamycin
Hydrochloride RS, prepare the standard solution with the
same procedure as the above test solution preparation.
the standard solution as directed under the Gas Chromatography according to the following operating conditions,
and determine the ratios, QT and QS, of the peak area of
clindamycin to that of the internal standard.
Amount [g (potency)] of clindamycin (C18H33ClN2O5S)

= amount [g (potency)] of Clindamycin Hydrochloride
RS
AT
AS
Mobile phase: Dissolve 6.8 g of potassium dihydrogen phosphate in water to make 1000 mL, and adjust the
pH to 7.5 with 8 mol/L potassium hydroxide solution. To
500 mL of this solution, add 500 mL of acetonitrile.
Clindamycin Hydrochloride
Capsules
Clindamycin Hydrochloride Capsules contains not less
Amount [g (potency)] of clindamycin (C18H33ClN2O5S)

= Amount [g (potency)] of Clindamycin Hydrochloride
RS
QT
QS
Internal standard solutionWeigh an appropriate

amount of cholestane, dissolve in pyridine to make a solution so that each mL contains 3 mg.
Detector: A hydrogen flame-ionization detector
Column: A glass column, about 3 mm in inside diameter and about 1 m in length, packed with diatomaceous earth washed with acid and alkali for gas chromatography impregnated with 1 % dimethyl polysiloxan
rubber.
KP 9 231
Column temperature: 200 C
Detector temperature: 215 C
Carrier gas: Helium
Flow rate: 120 mL per minute
Clindamycin Phosphate
CH3
H
N
H
N
Cl
mycin Phosphate is used in a sterile preparation. Weigh

an appropriate amount of Clindamycin Phosphate, dissolve in Isotonic Sodium Cholride Injection to make the
solution so that each mL contains 5.0 mg, and use the solution as the test solution. The amount of injection is 1.0
mL of the test solution per kg of body weight of rabbit.
Histamine It meets the requirement, when Clindamycin Phosphate is used in a sterile preparation. Weigh appropriate an amount of Clindamycin Phosphate, dissolve
in Isotonic Sodium Chloride Injection, make a solution
so that each mL contains 5 mg, and use the solution as
the test solution.
CH3
OH
O
H 3C
HO
CH3
O
HO

direct titration).
OH
C18H34ClN2O8PS: 504.97
Clindamycin Phosphate contains not less than 758 g
(potency) of per mg of clindamycin (C18H33ClN2O5S:
Description Clindamycin Phosphate is a whtie to pale
yellowish white crystalline powder.
Clindamycin Phosphate is freely soluble in water, sparingly soluble in methanol, and practically insoluble in
Identification (1) Proceed with Clindamycin Phosphate and Clindamycin Phosphate RS as directed in the
Identification (1) under Clindamycin Hydrochloride. Dry
0.2 g each of Clindamycin Phosphate and Clindamycin
Phosphate RS at 100 C for 2 hours, and keep them at
room temperature for 1 hour, and use them for the test.
(2) Weigh about 50 mg each of Clindamycin Phosphate and Clindamycin Phosphate RS, dissolve each in
10 mL of water, and use these solutions as the test solution and the standard solution. Perform the test as directed in the Identification (2) under Clindamycin Hydrochloride.
(3) An aqueous solution of Clindamycin Phosphate
responds to the Qualitative Tests for phosphate salt.
peak in the chromatogram obtained with the test solution
is the same as that of the principal peak in the chromatogram obtained with the standard solution.
of Clindamycin Phosphate in 10 mL of water is between 3.5 and 4.5.
Sterility Test It meets the requirement, when Clindamycin Phosphate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Clinda-
Assay Perform the test according to Assay in Clindamycin Hydrochloride. Use Clindamycin Phosphate RS as
the standard substance.
Clinofibrate
CH2CH3
O
CCO2H
CH3
CH3
O
CCO2H
CH2CH3
C28H36O6: 468.58
Clinofibrate, when dried, contains not less than 98.5%
and not more than 101.0% of clinofibrate (C28H36O6).
Description Clinofibrate is a white to yellowish white
powder, is odorless and has no taste.
Clinofibrate is freely soluble in methanol, in dehydrated
ethanol, in acetone or in ether and practically insoluble in
water.
A solution of Clinofibrate in methanol (1 in 20) shows no
optical rotation.
solutions of Clinofibrate and Clinofibrate RS in dehydrated ethanol (1 in 50000) under the Ultraviolet-visible
(2) Determine the infrared spectra of Clinofibrate and
Clinofibrate RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of

Purity (1) Heavy metalsProceed with 1.0 g of Clinofibrate according to Method 2 and perform the test.
Clinofibrate according to Method 3 and perform the test
(3) Related substancesDissolve 0.10 g of Clinofibrate in 10 mL of acetone and use this solution as the test
solution. Pipet 1 mL of the test solution and add acetone
to make exactly 50 mL. Pipet 5 mL of this solution, add
fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, cyclohexane and glacial acetic acid (12 : 5 : 3) to a distance of
about 12 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other
than the principal spot from the test solution are not more
intense than the spot from the standard solution.
Isomer ratio To 50 mg of Clinofibrate, add 0.4 mL of
thionyl chloride, stopper tightly, heat in a water-bath at
60 C for 5 minutes with occasional shaking and evaporate the excess thionyl chloride at a temperature not exceeding 60 C under reduced pressure. Dissolve the residue in 2 mL of toluene, previously dried with synthetic
zeolite for drying, add 2 mL of a solution of D-(+)-methylbenzylamine in toluene, previously dried with
synthetic zeolite for drying (3 in 100), mix gently, allow
to stand for 10 minutes and evaporate the toluene at a
temperature not exceeding 60 C under reduced pressure.
Dissolve the residue in 5 mL of chloroform and use this
solution as the test solution. Perform the test with 5 L
of the test solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area, Aa , Ab and Ac , of three peaks
appear in order near the retention time of 40 minutes: a
value, Ab /(Aa + Ab + Ac ) 100, is between 40 and 70.
about 20 C.
Mobile phase: A mixture of hexane and isopropanol
(500 : 3).
time of the peak appearing first is about 35 minutes.
Selection of column: Proceed with 5 L of the test

solution under the above operating conditions. Use a column giving a complete separation of the three peaks.
60 C, 3 hours).
Assay Weigh accurately about 0.45 g of Clinofibrate,
previously dried, dissolve in 40 mL of dehydrated ethanol, add 30 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination and make any necessary correction.

= 23.429 mg of C28H36O6
Clobetasol Propionate
O
H3C
H
H3C
O
Cl
HO
H
H3C
H
CH3
C25H32ClFO5: 466.97
Clobetasol Propionate, when dried, contains not less than
97.0% and not more than 102.0% of clobetasol propionate (C25H32ClFO5).
Description Clobetasol Propionate is a white crystalline powder.
Clobetasol Propionate is freely soluble in acetone or in
dichloromethane, sparingly soluble in ethanol and practically insoluble in water.
Melting point196 C (with decomposition).
Clobetasol Propionate and Clobetasol Propionate RS,
previously dried, respectively, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) The retention time of the principal peak in the
chromatogram of the Assay preparation corresponds to
that of the standard preparation, both relative to the internal standard, as obtained in the Assay.
KP 9 233
[ ]20
D : Between +96
and
+104 o (after drying, 0.1 g, 1,4-dioxane, 10 mL, 100

mm).
Purity Related substancesWeigh 10.0 mg of Clobetasol Propionate, dissolve in the mobile phase to make
100 mL and use this solution as the test solution (1). Pipet 1 mL of the test solution (1), add the mobile phase to
make exactly 50 mL and use this solution as the test solution (2). Separately, weigh accurately about 10 mg of
Clobetasol Propionate RS and about 5 mg of 9-Fluoro11-hydroxy-16-methyl-3-oxoandrosta-1,4-diene-17(R)
-spiro-2'-[4'-chloro-5'-ethylfurane-3-(2'H)-one] RS, dissolve in the mobile phase to make 100 mL and use this
10 L each of the test solutions (1) and (2) and the standard solution as directed under the Liquid Chromatography: the area of each peak other than the principal peak
of the test solution (1) is not more than 0.5 times (1.0%)
of the area of the principal peak of the test solution (2)
and the total peak areas of all related substances is not
more than 1.25 times (2.5%) of the area of the principal
peak of the test solution (2). But, omit the peak which
peak area is less than 0.025 times (0.05%) of the area of
the principal peak among the peaks of the test solution
(2).
potassium phosphate (adjust to pH 2.5 by adding phosphate), acetonitrile and methanol (425 : 475 : 100).
System suitability
above operating conditions, the resolution between their
peaks of Clobetasol Propionate and 9-fluoro-11-hydroxy16-methyl-3-oxoandrosta-1,4-diene-17(R)-spiro-2'-[4'chloro-5'-ethylfurane-3-(2'H) -one] is not less than 3.0.
hours).
Assay Weigh accurately about 10 mg each of Clobetasol Propionate and Clobetasol Propionate RS, previously
dried, dissolve each in mobile phase, add exactly 100 mL
of the internal standard solution, add mobile phase to
make 250 mL and use these solution as the test solution
with 10 L each of the test solution and the standard so-
lution as directed under Liquid Chromatography according to the operating conditions of the related substances
in Purity and calculate the ratios, QT and QS , of the
peak area of clobetasol propionate to that of the internal
standard for the test solution and the standard solution,
respectively.
Amount (mg) of clobetasol propionate (C25H32ClFO5)
= amount (mg) of Clobetasol Propionate RS
QT
QS
Internal standard solutionA solution of Beclometasone Dipropionate in mobile phase (1 in 5000).

Packaging and Storage Preserve in well-closed, lightresistant containers.
Clobetasol Propionate Cream

Clobetasol Propionate Cream contains not less than
of clobetasol propionate (C25H32ClFO5:466.97).
Creams, with Clobetasol Propionate.
Identification (1) Transfer, accurately weighed, a portion of Clobetasol Propionate Cream, equivalent to about
0.75 mg of clobetasol propionate(C25H32ClFO5), to a 25
mL centrifugal tube, add 10 mL of methanol, stopper,
heat in the water-bath at 60 C for 4 minutes, then take
out from the water-bath and extract while vigorously
shaking. Repeat this procedure several times, cool to
room temperature, add 3.5 mL of water and centrifuge
for about 10 minutes. Transfer 10 mL of a clear supernatant to a separator, add 1 g of sodium chloride and 10 mL
of water and mix well. To this solution, add 5 mL of
dichloromethane, extract after sonication for 1 minute,
take the dichloromethane layer, evaporate to dryness under the current of nitrogen, dissolve the residue in 0.5 mL
of dichloromethane and use this solution as the test solution. Proceed as directed in the Identification (1) under
Clobetasol Propionate Ointment.
chromatogram of the Assay preparation corresponds to
that of the standard preparation, both relative to the internal standard, as obtained in the Assay.
Assay Weigh accurately a portion of Clobetasol Propionate Cream, equivalent to about 1 mg of clobetasol
propionate (C25H32ClFO5), add 10 mL of dehydrated
ethanol, warm in a water-bath with frequent shaking until
the cream is completely dispersed and cool in the icebath for 30 minutes. Pipet 5 mL of clear solution after
centrifuge, add 5.0 mL of the internal standard solution,
mix well and use this solution as the test solution. With

this test solution, proceed as directed in the Assay under
Clobetasol Propionate Ointment.
Amount (mg) of clobetasol propionate(C25H32ClFO5)
QT
1
Q S 10
Internal standard solutionA solution of Beclometasone Dipropionate in 50% ethanol (1 in 5000).

Store at a temperature not exceeding 30 C.
Clobetasol Propionate Ointment
the ointment is completely dispersed and cool in the icebath for 30 minutes. Pipet exactly 5 mL of clear solution
after centrifuge, add 5 mL of the internal standard solution, mix well and use this solution as the test solution.
Separately, weigh accurately about 10 mg of Clobetasol
Propionate RS, dissolve in 50% ethanol to make 100 mL,
transfer exactly 5 mL of this solution to a volumetric
flask, add 5.0 mL of the internal standard solution, mix
well and use this solution as the standard solution. Perform the test with 10 L each of the test solution and the
standard solution as directed under Liquid Chromatography according operating to the following conditions and
Clobetasol Propionate to that of the internal standard, for
Amount (mg) of clobetasol propionate(C25H32ClFO5)
Clobetasol Propionate Ointment contains not less than

of clobetasol propionate (C25H32-ClFO5: 466.97).
Ointments, with Clobetasol Propionate.
Identification (1) Transfer a portion of Clobetasol
Propionate Ointment, equivalent to about 0.5 mg of clobetasol propionate (C25H32-ClFO5) according to the
labled amount, to a 25 mL centrifugal tube, add 10 mL of
methanol, stopper, heat in the water-bath at 70 C for 4
minutes, then take out from water-bath and extract while
vigorously shaking. Repeat this operation several times,
cool in the ice-bath for 5 minutes and centrifuge for
about 10 minutes. Pipet 5 mL of a clear supernatant, evaporate to dryness under the current of nitrogen, dissolve
the residue in 0.5 mL of dichloromethane and use this solution as the test solution. Separately, weigh about 10 mg
of Clobetasol Propionate RS, dissolve in dichloromethane to make 20 mL and use this solution as the standard solution. Perform the test with these solutions as directed and the Thin-layer Chromatography. Spot 10 L
dichloromethanes, acetone and absolute ethanol (100 :
nm): the principal spot from the test solution shows the
same Rf value as the principal spot from the standard
solution.
chromatogram of the test solution in Assay corresponds
to that of the standard solution, both relative to the internal standard, as obtained in the Assay.
Assay Weigh accurately a portion of Clobetasol Propionate Ointment, equivalent to about 1 mg of clobetasol
propionate (C25H32ClFO5), add 10 mL of absolute ethanol, warm in the water-bath with frequent shaking until
QT
1
Q S 10
Internal standard solutionA solution of Beclometasone Dipropionate in 50% ethanol (1 in 5000).

Mobile phase: A mixture of water and absolute ethanol (55 : 45).
Column temperature: 60 C.
Store at a temperature not exceeding 30 C.
Clofibrate
CH3 O
Cl
OC2H5
CH3
Cl2Hl5ClO3: 242.70
Clofibrate contains not less than 98.0% and not more
than 101.0% of clofibrate (Cl2Hl5ClO3), calculated on the
anhydrous basis.
Description Clofibrate is a colorless or pale yellow,
clear, oily liquid, has a characteristic odor and taste,
which is bitter at first and subsequently sweet.
Clofibrate is miscible with methanol, with ethanol, with
dehydrated ethanol, with ether or with hexane and practi-
KP 9 235
cally insoluble in water.
Clofibrate is gradually decomposed by light.
solutions of Clofibrate and Clofibrate RS in ethanol (1 in
10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similsr intensities of absorption at the same wavelengths. Determine the absorption spectra of solutions of Clofibrate and Clofibrate RS
in dehydrated ethanol (1 in 100000) as directed under the
Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Clofibrate and
Clofibrate RS as directed in the liquid film method under
Refractive Index
Specific Gravity
nD20 : Between 1.500 and 1.505.

20
: Between 1.137 and 1.144.
d 20
Purity (1) AcidDissolve 2.0 g of Clofibrate in 100

mL of neutralized ethanol and add 1 drop of phenolphthalein TS and 0.20 mL of 0.1 mol/L sodium hydroxide
VS: the solution is red in color.
(2) Heavy metalsProceed with 2.0 g of Clofibrate
(3) ArsenicTo 5.0 g of Clofibrate, add 20 mL of
nitric acid and 5 mL of sulfuric acid and heat until white
fumes are evolved. After cooling, if necessary, add further 5 mL of nitric acid, heat until white fumes are
evolved and repeat this procedure until the solution is colorless to pale yellow. After cooling, add 15 mL of saturated ammonium oxalate solution and heat again until
white fumes are evolved. Cool, add water to make 25 mL,
use 5 mL of this solution as the test solution and perform
Standard solutionPrepare a solution according to

the above procedure without using Clofibrate as the
blank. Transfer 5 mL of the solution to a generator bottle,
add 2.0 mL of standard arsenic solution and then proceed
as directed in the test solution.
(4) p-ChlorophenolTo 1.0 g of Clofibrate, add exactly 1 mL of the internal standard solution, then add the
mobile phase to make 5 mL and use this solution as the
test solution. Separately, dissolve 10 mg of pchlorophenol in a mixture of hexane and isopropanol (9 :
1) to make exactly 100 mL. Pipet 10 mL of this solution
and add a mixture of hexane and isopropanol (9 : 1) to
make exactly 50 mL. Pipet 6 mL of this solution, add exactly 4 mL of the internal standard solution, then add the
mobile phase to make exactly 20 mL and use this solu-
tion as the standard solution. Perform the test with 20 L

and QS , of the peak area of p-chlorophenol to that of the
solution, respectively: QT is not greater than QS .
Internal standard solutionA solution of pethoxyphenol in the mobile phase (1 in 30000).

Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with
cyanopropylsilanized silica gel for liquid chromatography (5 m to 10 m in particle diameter).
about 25 C.
Mobile phase: A mixture of hexane, isopropanol and
time of Clofibrate is about 2 minutes.
Selection of column: Dissolve 0.1 g of Clofibrate, 6
mg of p-chlorophenol and 6 mg of p-ethoxyphenol in
1000 mL of hexane. Proceed with 20 L of this solution
under the above operating conditions and calculate the
resolution. Use a column giving elution of Clofibrate, pchlorophenol and p-ethoxyphenol in this order, with the
resolution between the peaks of Clofibrate and pchlorophenol being not less than 5.0 and with the resolution between the peaks of p-chlorophenol and pethoxyphenol being not less than 2.0.
direct titration).
Assay Weigh accurately about 0.5 g of Clofibrate, add
exactly 50 mL of 0.1 mol/L potassium hydroxide-ethanol
VS and heat in a water-bath under a reflux condenser
with a carbon dioxide absorbing tube (soda lime) for 2
hours with frequent shaking. Cool and titrate immediately the excess potassium hydroxide with 0.1 mol/L hydrochloric acid VS (indicator: 3 drops of phenolphthalein
TS). Perform a blank determination and make any necessary connection.

= 24.270 mg of Cl2Hl5ClO3
tight containers.
Clofibrate Capsules
Clofibrate Capsules contain not less than 93.0% and not
more than 107.0% of the labeled amount of clofibrate
(Cl2Hl5C1O3: 242.70).
Capsules, with Clofibrate.
Prepare as directed under
Identification Open the capsules and use the contents.

Determine the absorption spectrum of a solution of the
contents in ethanol (1 in 10000) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 278 nm and 282 nm. Determine the absorption spectrum of a solution of the contents in ethanol
Spectrophotometry: it exhibits a maximum between 224
nm and 228 nm.
Purity p-ChlorophenolCut and open not less than
20 Clofibrate Capsules and proceed with 1.0 g of the
well mixed contents as directed in the Purity (4) under
Clofibrate.
about 25 C.
Mobile phase: A mixture of acetonitrile and diluted
phosphoric acid (1 in 1000) (3 : 2).
time of Clofibrate is about 10 minutes.
Selection of column: Dissolve 50 mg of Clofibrate
and 0.3 g of ibuprofen in 50 mL of acetonitrile. Proceed
conditions and calculate the resolution. Use a column
giving elution of ibuprofen and clofibrate in this order
with the resolution between their peaks being not less
than 6.0.
Clomifene Citrate

Assay Weigh accurately not less than 20 Clofibrate
Capsules, open the capsules, rinse the inside of the capsules with a small amount of ether after taking out the
contents, evaporate the ether by allowing the capsules to
stand at room temperature and weigh the capsules accurately. Weigh accurately an amount of the contents,
equivalent to about 0.1 g of clofibrate (Cl2Hl5C1O3), dissolve in acetonitrile to make exactly 100 mL. Pipet 5 mL
of this solution, add exactly 5 mL of the internal standard
solution and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Clofibrate RS,
proceed in the same manner as directed for the test solution and use this solution so obtained as the standard solution. Perform the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of the peak
area of Clofibrate to that of the internal standard, for the
Amount (mg) of cloabrate (Cl2Hl5C1O3)

= amount (mg) of Clofibrate RS,
QT
QS
Interanl standard solutionA solution of ibuprofen

in the mobile phase (1 in 100).
Cl
CH2CO 2H
C
C
OCH 2CH2N(CH 2CH3)2
HO
CO 2H
CH2CO 2H
C26H28ClNOC6H8O7: 598.08
Clomifene Citrate, when dried, contains not less than
98.0% and not more than 101.0% of clomifene citrate
(C26H28ClNOC6H8O7).
Description Clomifene Citrate is a white to pale yellowish white powder and is odorless.
Clomifene Citrate is freely soluble in methanol or in glacial acetic acid, soluble in ethanol, sparingly soluble in
water and practically insoluble in ether.
Clomifene Citrate is gradually colored by light.
Melting pointAbout 115 C
Identification (1) To 2 mL of a solution of Clomifene
Citrate in butanol (1 in 200), add 2 mL of Reinecke salt
TS: a light red precipitate is produced.
Clomifene Citrate and Clomifene Citrate RS in 0.1 mol/L
hydrochloric acid TS (1 in 50000) as directed under the
(3) A solution of Clomifene Citrate in methanol (1 in
200) responds to the Qualitative Tests (1) and (2) for ci-
KP 9 237
trate salt.
Purity (1) Clarity and color of solutionThe solution
of 1.0 g of Clomifene Citrate in 30 mL of methanol is
(2) Heavy metalsProceed with 2.0 g of Clomifene
Citrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
P2O5, 3 hours).
Isomer Ratio To 0.10 g of Clomifene Citrate, add 10
mL of water and 1 mL of sodium hydroxide TS and extract with three 15 mL volumes of ether. Wash the combined ether extracts with 20 mL of water, add 10 g of anhydrous sodium sulfate to the combined ether extracts,
shake for 1 minute, filter and evaporate the ether of the
filtrate. Dissolve the residue in 10 mL of chloroform and
use this solution as the test solution. Perform the test
with 2 L of the test solution as directed under the Gas
Determine the areas of two adjacent peaks, Aa and Ab ,
having retention times of about 20 minutes, where Aa

is the peak area of shorter retention time and Ab is the
peak area of longer retention time: Ab /( Aa + Ab ) is between 0.3 and 0.5.
and about 1 m in length, having methylsilicone polymer
coated at the ratio of 1% on siliceous earth for gas chromatography (125 m to 150 m in particle diameter).
about 195 C.
time of the peak for the first elution of clomifene citrate
is about 20 minutes.
solution under the above operating conditions: use a column giving the resolution between the two peaks being
not less than 1.3.
Assay Weigh accurately about 1 g of Clomifene Citrate,
previously dried, dissolve in 50 mL of glacial acetic acid
and titrate with 0.1 mol/L perchloric acid VS (indicator:

= 59.81 mg of C26H28ClNOC6H8O7

tight containers.
Clomifene Citrate Tablets

Clomifene Citrate Tablets contain not less than 93.0%
and not more than 107.0% of the labeled amount of the
clomifene citrate (C26H28ClNOC6H8O7: 598.08).
Method of Preparation Prepare as directed under Tablets, with Clomifene Citrate.
Identification Weigh a portion of powdered Clomifene
Citrate Tablets, equivalent to 1 g of Clomifene Citrate
according to the labeled amount, shake vigorously with
100 mL of chloroform and filter. Concentrate the filtrate
in a water-bath, allow to stand at room temperature, collect the crystals formed and wash with a small volume of
chloroform. Proceed with the crystals as directed in the
Identification under Clomifene Citrate.
Uniformity of Dosage Limits It meets the requirement
Clomifene Citrate Tablets. Weigh accurately a portion of
the powder, equivalent to about 50 mg of clomifene citrate (C26H28ClNOC6H8O7), add 50 mL of methanol,
shake for 10 minutes and add methanol to make exactly
100 mL. Centrifuge a volume of this solution, pipet 4.0
mL of the supernatant liquid, add methanol to make exactly 100 mL and use this solution as the test solution.
Separately, weigh accurately 50 mg of Clomifene Citrate
RS, previously dried in a desiccator (in vacuum, P2O5)
for 3 hours and dissolve in methanol to make 100 mL.
Pipet 4.0 mL of this solution and dilute with methanol to
make exactly 100 mL and use this solution as the standard solution. Determine the absorbances as directed under the Ultraviolet-visible Spectrophotometry, AT and
AS , of the test solution and the standard solution, respectively, at 295 nm.
Amount (mg) of clomifene citrate (C26H28ClNOC6H8O7)
= amount (mg) of Clomifene Citrate RS
AT
AS
Clomipramine Hydrochloride
N
Cl
CH3
HCl
CH2CH2CH2N
CH3
C19H23ClN2HCl: 351.31
Clomipramine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of clomipramine hydrochloride (C19H23ClN2HCl).
Description Clomipramine Hydrochloride is a white to
pale yellow, crystalline powder and is odorless.
Clomipramine Hydrochloride is very soluble in glacial
acetic acid, freely soluble in water, in methanol or in
chloroform, soluble in ethanol, sparingly soluble in acetic anhydride, slightly soluble in acetone and practically
insoluble in ethyl acetate or in ether.
Identification
(1) Dissolve 3 mg of Clomipramine
Hydrochloride in 1 mL of nitric acid: a deep blue color is
observed.
Clomipramine Hydrochloride and Clomipramine Hydrochloride RS in 0.1 mol/L hydrochloric acid TS (3 in
(3) Take 1 g of Clomipramine Hydrochloride in a separator, dissolve in 10 mL of water, add 5 mL of sodium
hydroxide TS and extract with two 30 mL volumes of
ether [the water layer is used for Identification (4)].
Combine the ether extracts, add 20 mL of water and
shake. Take ether layer, dry with a small portion of anhydrous sodium sulfate and filter. Evaporate the combined extracts by warming a water-bath and proceed the
test with the residue as directed under the Flame Coloration Test (2): a green color is observed.
(4) The solution neutralized by adding dilute nitric
acid to the water layer obtained in (3) responds to the
Clomipramine Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.20 g of Clomipramine Hydrochloride in exactly 10 mL of methanol
weigh 20 mg of Imipramine Hydrochloride RS, dissolve
in methanol to make exactly 100 mL and use this solution as the standard solution (1). Then pipet 1 mL of the
test solution and add methanol to make exactly 50 mL.
Pipet 5 mL of this solution, add methanol to make exactly 50 mL and use this solution as the standard solution
(2). Perform the test with the test solution and the standard solutions (1) and (2) as directed under the Thinlayer Chromatography. Spot 5 L of the test solution and
the standard solutions (1) and (2) on a plate of silica gel
mixture of ethyl acetate, acetone and strong ammonia
water (15 : 5 : 1) to a distance of 10 cm and air-dry the
plate. Spray evenly potassium dichromate-sulfuric acid
TS on the plate: the spots from the test solution corresponding to that from the standard solution (1) is not more
intense than the spot from standard solution (1). Each of
the spots other than the principal spot and the above spot
from the standard solution (2).
hours).
Assay Weigh accurately about 0.5 g of Clomipramine
Hydrochloride, previously dried, dissolve in 50 mL of a

= 35.131 mg of C19H23ClN2HCl

pH Dissolve 1.0 g of Clomipramine Hydrochloride in
and 5.0.
g of Clomipramine Hydrochloride in 10 mL of water: the
solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 2.0 g of Clomipramine Hydrochloride according to Method 2 and perform
Clonazepam
KP 9 239
H
N
O2N
N
Cl
C15H10ClN3O3: 315.71
Clonazepam, when dried, contains not less than 99.0%
and not more than 101.0% of clonazepam
(C15H10ClN3O3).
Description Clonazepam is a white to pale yellow,
crystal or crystalline powder.
Clonazepam is sparingly soluble in acetic anhydride or
acetone, slightly soluble in methanol or in ethanol, very
Clonazepam is gradually colored by light.
solutions of Clonazepam and Clonazepam RS in methanol (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Clonazepam
and Clonazepam RS, previously dried, as directed in the
absorption at the same wave numbers.
(3) Perform the test with Clonazepam as directed under the Flame Coloration Test (2): a green color appears.
Purity (1) ChlorideTo 1.0 g of Clonazepam, add 50
mL of water, allow to stand for 1 hour with occasional
shaking and filter. Discard the first 20 mL volumes of the
filtrate, take the subsequent 20 mL volumes of the filtrate
and add 6 mL of dilute nitric acid and water to make 50
mL. Use this solution as the test solution and perform the
test. Prepare the control solution as follows: take 0.25ml
of 0.01 mol/L hydrochloric acid VS and add 6 mL of dilute nitric acid and water to make 50 mL (not more than
0.022%).
(2) Heavy metalsProceed with 1.0 g of Clonazepam
(3) Related substancesDissolve 0.25 g of Clonazepam in 10.0 mL of acetone and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add acetone to make exactly 100 mL, then pipet 1.0 mL of this
solution, add acetone to make exactly 10 mL and use this
silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of nitromethane and acetone (10 : 1) to a distance of about 12
hours).
Assay Weigh accurately about 0.5 g of Clonazepam,
previously dried, dissolve in 70 mL of acetic anhydride

= 31.571 mg of C15H10ClN3O3

Clonidine Hydrochloride
Cl
H
N
NH
HCl
Cl
C9H9Cl2N3HCl: 266.56
Clonidine Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of clonidine hydrochloride (C9H9Cl2N3HCl).
Description Clonidine Hydrochloride is a white crystal
Clonidine Hydrochloride is very soluble in methanol, soluble in water or in ethanol, slighlty soluble in glacial
acetic acid and practically insoluble in acetic anhydride
or ether.
Identification (1) To 5 mL of a solution of Clonidine
Hydrochloride (1 in 1000), add 6 drops of Dragendorfs
TS: an orange precipitate is produced.
Clonidine Hydrochloride and Clonidine Hydrochloride
RS in 0.01 mol/L hydrochloride VS (3 in 10000), as directed under the Ultraviolet-visible Spectrometry: both
same wavelengths.
(3) Determine the infrared spectra of Clonidine Hy-

drochloride and Clonidine Hydrochloride RS, previously
dried, as directed in potassium chloride disk method under the Infrared Spectorphotometry: both spectra exhibit
(4) A solution (1 in 50) of Clonidine Hydrochloride
pH Dissolve 1.0 g of Clonidine Hydrochloride in 20
5.5.
Purity (1) Clarity and color of solutionThe solution
of 1.0 g of Clonidine Hydrochloride in 20 mL of water, is
(2) Heavy metalsProceed with 2.0 g of Clonidine
Hydrochloride according to Method 1,.and perform the
Clonidine Hydrochloride, according to Method 3 and
(4) Related substancesDissolve 0.20 g of Clonidine Hydrochloride in 2.0 mL of methanol and use this
solution as the test solution. Pipet 1.0 mL of the test solution and add methanol to make exactly 100 mL. Take
each 1.0 mL and 2.0 mL volumes of this solution, add
methanol to make exactly 20 mL each and use these solutions as the standard solutions (1) and (2), respectively.
solutions (1) and (2) as directed under the Thin-layer
Chromatography. Spot each 2 L of the test solution and
the standard solutions (1) and (2) on the plate of silica
gel. Develop the plate with a mixture of toluene, dioxane,
absolute ethanol and strong ammonia water (10 : 8 : 2 :
1) to a distance of 12 cm and air-dry the plate. Dry the
plate at 100 C for 1 hour, spray evenly sodium hypochlorite TS and air-dry the plate for 15 minutes. Then,
spray evenly potassium iodide-starch TS to the plate. The
spots other than the principal and original spots are not
more intense than the spot from standard solution (2) and
the number of spots, which are more intense than the
spot from standard solution (1), other than the principal
and original spots is not more than 3.
hours).
Assay Weigh accurately 0.4 g of Clonidine Hydrochloride, previously dried, dissolve in 30 mL of glacial acetic
and warm to dissolve. Cool, add 70 mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 26.656 mg of C9H9Cl2N3HCl
Cloperastine Hydrochloride
HCl
O
N
Cl
and enatiomer
C20H24ClNOHCl: 366.33
Cloperastine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of cloperastine hydrochloride (C20H24ClNOHCl).
Description Cloperastine Hydrochloride is a white
Cloperastine Hydrochloride is very soluble in water, in
methanol, in ethanol or in glacial acetic acid, and sparingly soluble in acetic anhydride.
A solution of Cloperastine Hydrochloride (1 in 10)
solutions of Cloperastine Hydrochloride and Cloperastine Hydrochloride RS in 0.1 mol/L hydrochloric acid TS
(1 in 2500) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Cloperastine
Hydrochloride and Cloperastine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) Shake 10 mL of a solution of Cloperastine Hydrochloride (1 in 100) with 2 mL of ammonia TS and 20
mL of ether, and filter. Acidify the filtrate with dilute nitric acid: the solution responds to the Qualitative Tests
for chloride.
Melting Point
Purity (1) Heavy metalsProceed with 1.0 g of Cloperastine Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
of standard lead solution (not more than 20 ppm).
KP 9 241
(3) Related substancesDissolve 40 mg of Cloperastine Hydrochloride in 50 mL of the mobile phase and
use this solution as the test solution. Pipet 1.0 mL of the
test solution and add the mobile phase to make exactly
the standard solution as directed under the Liquid Chromatography, according to the following conditions, and
determine each peak area of both solutions by the automatic integration method: the areas of two peaks corresponding to the relative retention times of about 0.8 and
3.0 to the retention time of cloperastine obtained from
the test solution are not larger than the peak area from
the standard solution, respectively, and the area of the
peak corresponding to the relative retention time of about
2.0 to cloperastine is not larger than 5/3 of the peak area
from the standard solution, and the areas of the peaks
other than cloperastine and other than the peaks mentioned above are all not larger than 3/5 of the peak area
from the standard solution. The total area of these peaks
is not larger than 2 times of the peak area of cloperastine
from the standard solution .
about 25 C.
Mobile phase: A mixture of methanol, 0.1 mol/L monobasic potassium phosphate TS and perchloric acid
(500:250:1).
time of cloperastine is about 7 minutes.
Selection of column: Dissolve 30 mg of Cloperastine
Hydrochloride and 40 mg of benzophenone in 100 mL of
the mobile phase. To 2.0 mL of this solution add the mobile phase to make 50 mL. Perform the test with 20 L of
this solution under the above operating conditions: Use a
column giving elution of cloperastine and benzophenone
in this order with the resolution between these peaks being not less than 6.
so that the peak height of cloperastine obtained from 20
L of the standard solution is about 30% of the full scale.
the retention time of cloperastine, beginning after the
solvent peak.
hours).
Assay Weigh accurately about 0.5 g of Cloperastine
mixture of acetic anhydride and glacial acetic acid (7:3)

= 36.63 mg of C20H24ClNOHCl
tight containers.
Clotiazepam
CH3
O
C2H5
N
Cl
Cl6H15ClN2OS: 318.82
Clotiazepam, when dired, contains not less than 98.5%
and not more than 101.0% of clotiazepam
(Cl6H15ClN2OS).
Description Clotiazepam is a white to pale yellowish
white crystal or crystalline powder, is odorless and has a
slightly bitter taste.
Clotiazepam is very soluble in chloroform, freely soluble
in methanol, in ethanol, in acetone, in glacial acetic acid
or in ethyl acetate, soluble in ether and practically insoluble in water.
Clotiazepam dissolves in 0.1 mol/L hydrochloric acid TS.
Clotiazepam is gradually colored by light.
Identification (1) Dissolve 10 mg of Clotiazepam in 3
mL of sulfuric acid: the solution shows a pale yellow
fluorescent under ultraviolet light.
Clotiazepam and Clotiazepam RS in 0.1 mol/L hydrochloric acid TS (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra of absorption exhibit similar intensities at the same wavelengths.
(3) Prepare the test solution with 10 mg of Clotiazepam as directed under the Oxygen Flask Combustion
Method, using 10 mL of diluted strong hydrogen peroxide water (1 in 5) as the absorbing liquid. Apply a small
amount of water to the upper part of the Apparatus A,
pull out C carefully, wash C, B and the inner side of A
with 15 mL of methanol and use the obtained solution as
the test solution. Add 0.5 mL of dilute nitric acid to 15
mL of the test solution: this solution responds to the
Qualitative Tests (2) for chloride. The remaining test so-

lution responds to the Qualitative Tests (1) for sulfate.
Melting Point
tight containers.

g of Clotiazepam in 10 mL of ethanol: the solution is
solution.
Clotrimazole
Control solutionTo 5 mL of Color Matching Fluid

C, add 0.01 mol/L hydrochloric acid TS to make 10 mL.
(2) ChlorideTo 1.0 g of Clotiazepam, add 50 mL
of water, shake for 30 minutes and filter. To 30 mL of
the filtrate, add 6 mL of dilute nitric acid and water to
test solution. Prepare the control solution with 0.25 mL
0.015%).
(3) Heavy metalsProceed with 2.0 g of Clotiazepam according to Method 4 and perform the test. Prepare
the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Clotiazepam, according to Method 3 and perform the test
(5) Related substancesDissolve 0.25 g of Clotiazepam in 10.0 mL of acetone and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add acetone to make exactly 20 mL, pipet 2.0 mL of this solution, add acetone to make exactly 50 mL and use this solution as the standard solution. Perform the test with the
gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform
and acetone (5 : 1) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
hours).
Residue on Ignition
Assay Weigh accurately about 0.5 g of Clotiazepam,

and titrate with 0.1 mol/L perchloric acid (potentiometric

= 31.882 mg of Cl6H15ClN2OS
N
C
Cl
C22H17ClN2: 344.84
Clotrimazole, when dried, contains not less than 98.0%
and not more than 101.0% of clotrimazole (C22H17ClN2).
Description Clotrimazole is a white, crystalline powder, is odorless and tasteless.
Clotrimazole is freely soluble in dichloromethane or in
glacial acetic acid, soluble in dimethylformamide, in methanol or in ethanol, slightly soluble in ether and practically insoluble in water.
Identification (1) Dissolve 0.1 g of Clotrimazole in 10
mL of 5 mol/L hydrochloric acid TS by heating and cool.
To this solution, add 3 drops of Reinecke salt TS: a pale
red precipitate is produced.
Clotrimazole and Clotrimazole RS in methanol (1 in
(3) Determine the infrared spectra of Clotrimazole
and Clotrimazole RS, previously dried, as directed in the
(4) Perform the test with Clotrimazole as directed
Melting Point

g of Clotrimazole in 10 mL of dichloromethane: the solution is clear and colorless.
(2) ChlorideDissolve 1.0 g of Clotrimazole in 40
mL of dimethylformamide, add 6 mL of dilute nitric acid
and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution
with 0.60 mL of 0.01 mol/L hydrochloric acid VS, 40
mL of dimethylformamide, 6 mL of dilute nitric acid and
KP 9 243
water to make 50 mL (not more than 0.021%).
(3) SulfateDissolve 0.5 g of Clotrimazole in 10
mL of methanol and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this
methanol, 1 mL of dilute hydrochloric acid and water to
(4) Heavy metalsProceed with 2.0 g of Clotrimazole according to Method 2 and perform the test. Prepare
Clotrimazole according to Method 3 and perform the test
(6) ImidazoleDissolve 0.10 g of Clotrimazole in
exactly 10 mL of dichloromethane and use this solution
as the test solution. Separately, dissolve 25.0 mg of imidazole RS in dichloromethane to make exactly 50 mL.
Pipet 5.0 mL of this solution, add dichloromethane to
standard solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the
methanol and chloroform (3 : 2) to a distance of about 10
cm and air-dry the plate. Spray evenly sodium hypochlorite TS on the plate and air-dry the plate for 15 minutes,
then spray evenly potassium iodide-starch TS on the
plate: the spot from the test solution, corresponding to
that from the standard solution, is not more intense than
that from the standard solution.
(7) (2-Chlorophenyl)-diphenylmethanolDissolve
0.20 g of Clotrimazole in dichloromethane to make exactly 10 mL and use this solution as the test solution.
Separately, dissolve 10.0 mg of (2-chlorophenyl)diphenylmethanol RS in dichloromethane to make exactly 100 mL and use this solution as the standard solution.
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of ethyl acetate and strong ammonia water (50 : 1) to a distance of about 10 cm and air-dry the
254 nm): the spot from the test solution, corresponding
to that from the standard solution, is not more intense
than that from the standard solution.
hours).
Assay Weigh accurately about 0.35 g of Clotrimazole,
previously dried and dissolve in 80 mL of glacial acetic
acid and titrate with 0.1 mol/L perchloric acid VS (poten-
tiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 34.484 mg of C22H17ClN2

Cloxacillin Sodium Hydrate

NaO
O
H
O
N
CH3
Cl
CH3
N
H
S
H
O
CH3
H2O
C19H17ClN3NaO5SH2O: 475.88
Cloxacillin Sodium Hydrate contains not less than 825
g
(potency)
of
per
mg
of
cloxacillin
(C19H17ClN3NaO5S: 435.88), calculated on the anhydrous basis.
Description Cloxacillin Sodium Hydrate is a whtie to
yellow-white crystals or crystalline powder.
Cloxacillin Sodium Hydrate is freely soluble in water or
in methanol, sparingly soluble in ethanol, and slightly soluble in ether.
Cloxacillin Sodium Hydrate and Cloxacillin Sodium Hydrate RS as directed in potassium bromide disk method
under Infrared Spectrophotometry, both spectra exhibit
similar intensities of absorption at the wave numbers
about 1765 cm 1 , 1658 cm 1 , 1600 cm 1 , 1495
cm 1 , 1410 cm 1 , 1335 cm 1 , and 770 cm 1 .
(2) To 2 mg of Cloxacillin Sodium Hydrate in test
tube, add 2 mg of chromotrophic acid and 2 mL of sulfuric acid, and heat at 150 o C : the color of solution turns
to olive-green after one to 1.5 minutes, after 2 minutes
changes to deep red, and the test sample is carbonized to
become gradually black.
(3) Cloxacillin Sodium Hydrate responds to the Qualitative Tests for sodium salt.
of Cloxacillin Sodium Hydrate in 10 mL of water is between 4.5 and 7.5.
Sterility Test It meets the requirement, when Cloxacillin Sodium Hydrate is used in a sterile preparation.

cloxacillin, when Cloxacillin Sodium Hydrate is used in
a sterile preparation.
Water Between 3.0 % and 5.0 % (0.2 g, volumetric titration, direct titration).
Cloxacillin Sodium Hydrate and Cloxacillin Sodium Hydrate RS, dissolve in water to make exactly 50 mL, and
solution, respectively. Perform the test with 10 L of
peak areas, AT, and AS, of cloxacillin.
Amount [g (potency)] of cloxacillin

(C19H17ClN3NaO5S)
= Amount [g (potency)] of Cloxacillin Sodium Hydrate
RS
AT
AS
Mobile phase: Dissolve 2.72 g of potassium dihydrogen phosphate in water to make 1000 mL, and adjust the
pH to 5.0 with 8 mol/L potassium hydroxide solution. To
1000 mL of this solution, add 500 mL of acetonitrile.
Cloxazolam
O
H
N
O2N
O
Cl
and enantiomer
C17H14Cl2N2O2: 349.21
Cloxazolam, when dried, contains not less than 99.0%

and not more than 101.0% of cloxazolam
(C17H14Cl2N2O2).
Description Cloxazolam is a white crystal or crystalline powder, is odorless and tasteless.
Cloxazolam is freely soluble in glacial acetic acid, sparingly soluble in dichloromethane, slightly soluble in de-
hydrated ethanol or in ether, very slightly soluble in

ethanol and practically insoluble in water.
Cloxazolam dissolves in dilute hydrochloric acid.
Cloxazolam is gradually colored by light.
Identification (1) Dissolve 10 mg of Cloxazolam in 10
mL of dehydrated ethanol by heating and add 1 drop of
hydrochloric acid: the solution shows a pale yellow color
and a yellow-green fluorescence under ultraviolet light
(main wavelength: 365 nm). Add 1 mL of sodium hydroxide TS to this solution: the color and fluorescence of
this solution disappear immediately.
(2) Dissolve 10 mg of Cloxazolam in 5 mL of dilute
hydrochloric acid by heating in a water-bath for 10 minutes. After cooling, 1 mL of this solution responds to
the Qualitative Tests for primary aromatic amines.
(3) Place 2 g of Cloxazolam in a flask, add 50 mL of
ethanol and 25 mL of sodium hydroxide TS and boil under a reflux condenser for 4 hours. After cooling, neutralize with dilute hydrochloric acid and extract with 30 mL
of dichloromethane. Dehydrate with 3 g of anhydrous
sodium sulfate, filter and evaporate the dichloromethane
of the filtrate. Dissolve the residue in 5 mL of methanol
by heating in a water-bath and cool immediately in an
ice-bath. Collect the crystals and dry the crystals in vacuum at 60 C for 1 hour: it melts between 87 C and 91
C.
Cloxazolam and Cloxazolam RS in ethanol (1 in 100000)
as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities at the same
wavelengths.
(5) Proceed with Cloxazolam as directed under the
Flame Coloration Test (2): a green color appears.
%
Absorbance E11cm
(after drying, 1 mg, ethanol, 100 mL).
Purity (1) ChlorideTo 1.0 g of Cloxazolam, add 50

mL of water, allow to stand for 1 hour with occasional
shaking and filter. To 25 mL of this filtrate, add 6 mL of
dilute nitric acid and water to make 50 mL and perform
the test using this solution as the test solution. Prepare
the control solution with 0.20 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014%).
(2) Heavy metalsProceed with 1.0 g of Cloxazolam according to Method 2 and perform the test. Prepare
(3) ArsenicPlace 1.0 g of Cloxazolam in a Kjeldahl flask, add 5 mL of sulfuric acid and 5 mL of nitric
acid and heat gently. Repeat the addition of 2 mL to 3
mL of nitric acid at times and continue heating until a colorless to pale yellow solution is obtained. After cooling,
add 15 mL of saturated ammonium oxalate solution and
heat the solution until dense white fumes are evolved and
evaporate to a volume of 2 mL to 3 mL. After cooling,
KP 9 245
dilute with water to make 10 mL and perform the test
with this solution as the test solution (not more than 2
ppm).
(4) Related substancesDissolve 50.0 mg of Cloxazolam in 10.0 mL of dichloromethane and use this solution as the test solution. Pipet 1.0 mL of this solution,
add dichloromethane to make exactly 200 mL and use
chromatography. Immediately after air-drying, develop
the plate with a mixture of toluene and acetone (5 : 1) to
a distance of about 10 cm and air-dry the plate. Examine
are not more intense than that from the standard solution.
hours).
Assay Weigh accurately about 0.5 g of Cloxazolam,
acid. Titrate with 0.1 mol/L perchloric acid VS until the
color of the solution changes from purple through blue to
blue-green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and make any

= 34.921 mg of C17H14Cl2N2O2
tight containers.
Cocaine Hydrochloride
O
H
OCH 3
H
O
O
C
HCl
NCH3
soluble in ethanol or in glacial acetic acid, slightly soluble in acetic anhydride, and practically insoluble in
ether.
solutions of Cocaine Hydrochloride and Cocaine Hydrochloride RS in 0.01 mol/L hydrochloric acid TS (1 in
10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the absorption spectra of solutions of Cocaine Hydrochloride and
Cocaine Hydrochloride RS in 0.01 mol/L hydrochloric
acid TS (1 in 50000) as directed under the Ultravioletvisible spectrophotometry: both spectra exhibit similar
intensities of absorption at the same wavelengths
(2) Determine the infrared spectra of Cocaine Hydrochloride and Cocaine Hydrochloride RS, previously dried,
the Infrared Spectrophotometry: both spectra exhibit the
similar intensities at the same wavenumbers.
(3) A solution of Cocaine Hydrochloride (1 in 50) responds to the Qualitative Tests (2) for chlorides.
D : Between -70 and 73 (after drying, 0.5 g, water, 20 mL, 100 mm).
Purity (1) AcidityDissolve 0.5 g of Cocaine Hydrochloride in 10 mL of water, add 1 drop of methyl red
TS, and titrate with 0.01 mol/L sodium hydroxide VS:
not more than 1.0 mL is required to obtain a yellow color.
(2) CinnamylcocaineDissolve 0.10 g of Cocaine
Hydrochloride in 5 mL of water, and add 0.3 mL of diluted sulfuric acid (1 in 20) and 0.10 mL of 0.02 mol/L
potassium permanganate VS: the violet color does not
disappear entirely within 30 minutes.
(3) Isoatropy cocaineDissolve 0.10 g of Cocaine
Hydrochloride in 30 ml of water in a beaker. Transfer 5
ml of this solution to a test tube, add 1 drop of ammonia
TS, and mix. After the precipitate is coagulated, add 10
ml of water, and transfer the mixture to the former beaker,
to which 30 ml of water has been added previously. Wash
the test tube with 10 ml of water, combine the washing
with the mixture in the beaker, add 3 drops of ammonia
TS to the combined mixture, and mix gently: a crystalline precipitate is produced. Allow to stand for 1 hour:
the supernatant liquid is clear.
Loss on Drying Not more than 1.0% ( 1 g, 105 C, 4

hours).
C17H21NO4HCl: 339.81
Cocaine Hydrochloride, when dried, contains not less
than 98.0% and not more than 101.0% of cocaine hydrochloride (C17H21NO4HCl).
Description Cocaine Hydrochloride is a colorless crystal or white crystalline powder.
Cocaine Hydrochloride is very soluble in water, freely

Assay Weigh accurately 0.5 g of Cocaine Hydrochloride, previously dried, dissolve in 50 mL of a mixture of
acetic anhydride and glacial acetic acid (7 : 3), and titrate
a blank determination, and make any necessary correction.

KP 9 247
C18H21NO3H3PO41/2H2O: 406.37
Cod Liver Oil

Cod Liver Oil is the fatty oils obtained from fresh livers
and pyloric appendages of Gadus macrocephalus Tilesius
or Theraga chalcogramma Pallas (Gadidae).
Cod Liver Oil contains not less than 2000 vitamin A
units and not more than 5000 vitamin A units per g.
Description Cod Liver Oil is a yellow to orange oily
liquid, has a characteristic, slightly fishy odor and a mild
taste.
Cod Liver Oil is miscible with chloroform, with ether or
with pertroleum ether.
Cod Liver Oil is slightly soluble in ethanol.
Decomposition of Cod Liver Oil is accelerated by air or
by light.
Identification Dissolve 0.1 g of Cod Liver Oil in 10
mL of chloroform, and to 1 mL of this solution, add 3
mL of antimony trichloride TS: a blue color is observed
immediately, but the color fades rapidly.
Specific Gravity
20
: Between 0.918 and 0.928.
d 20
Acid Value Not more than 1.7.

Iodine Value Between 130 and 170.
Saponification Value Between 180 and 192.
Unsaponifiable Matter Not more than 3.0%
Purity RancidityNo unpleasant odor of rancid oil is
perceptible on warming Cod Liver Oil.
Assay Perform the test with about 0.5 g of Cod Liver
Oil, weighed accurately, as directed in Method 2 under
the Vitamin A Determination.
tight containers and almost well-filled or under nitrogen
atmosphere.
Codeine Phosphate Hydrate

CH3
N
H3PO4
O
CH3O
Codeine Phosphate
H OH
1/2 H2O
Codeine Phosphate Hydrate contains not less than 98.0

and not more than 101.0% of codeine phosphate
(C18H21NO3H3PO4: 397.36), calculated on the anhydrous
basis.
Description Codeine Phosphate Hydrate is a white
yellowish white crystal or crystalline powder.
Codeine Phosphate Hydrate is freely soluble in water
in glacial acetic acid, slightly soluble in methanol or
pHA solution of Codeine Phosphate Hydrate (1
10) is between 3.0 and 5.0.
Codeine Phosphate Hydrate is affected by light.
to
or
in
in

solutions of Codeine Phosphate Hydrate and Codeine
Phosphate Hydrate RS (1 in 10000) as directed under the
Codeine Phosphate Hydrate and Codeine Phosphate Hydrate RS, previously dried at 105 C for 4 hours, as directed in the potassium bromide disk method under the
(3) A solution of Codeine Phosphate Hydrate (1 in
20) responds to the Qualitative Tests (1) for phosphate.
D : Between -98 and 102 (0.4 g calculated on the anhydrous basis, water, 20
mL, 100 mm).
Purity (1) ChloridePerform the test with 0.5 g of
Codeine Phosphate Hydrate. Prepare the control solution
more than 0.021%).
(2) SulfatePerform the test with 0.20 g of Codeine
Phosphate Hydrate. Prepare the control solution with 1.0
0.240%).
(3) Related substances Dissolve 0.20 g of Codeine
Phosphate Hydrate in 10.0 mL of a mixture of 0.01
mol/L hydrochloric acid TS and dehydrated ethanol (4 :
1) and use this solution as the test solution. Pipet 1.0 mL
of the test solution, add a mixture of 0.01 mol/L hydrochloric acid TS and dehydrated ethanol (4 : 1) to make exactly 100 mL and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of dehydrated ethanol, toluene, acetone
and strong ammonia water (14 : 14 : 7 : 1) to a distance
of about 10 cm and air-dry the plate. Examine under ul-

traviolet light (main wavelength: 254 nm): the spots other than the principal spot from the test solution are not
Asssy Dissolve about 0.5 g of Codeine Phosphate Hydrate, accurately weighed, in 70 mL of glacial acetic acid
greenish blue (indicator: 3 drops of methylrosaniline
Amount (mg) of codeine phosphate hydrate

(C18H21NO3H3PO41/2 H2O)
= amount (mg) of Codeine Phosphate RS,
calculated on the anhydrous basis 1.0227
QT
QS
Internal Standard soultionA solution of etilefline

hydrochloride (3 in 10000).

= 39.736 mg of C18H21NO3H3PO4
tight containers.
tion as the standard solution. Perform the test with 20 L

the following operating conditions and calculate the ratios, QT and QS , of the peak area of codeine to that of
solutions, respectively.
1% Codeine Phosphate powder
the operating conditions in the Assay under 10% Codeine
Phosphate Powder.
1 % Codeine Phosphate Powder contains not less than

0.90% and not more the 1.10% of codeine phosphate hydrate (C18H21NO3H3PO41/2H2O: 406.37).
Codeine Phosphate Hydrate
10 g
Lactose
a sufficient quantity
To make 1000 g
Prepare as directed under Powders, with the above ingredients.
Identification Determine the absorption spectrum of a
solution of 1 % Codeine Phosphate Powder (1 in 100) as
it exhibits a maximum between 283 nm and 287 nm.
Particle Size Distribution Test for preparations
quirement.
It
It meets the re-
Assay Weigh accurately about 5 g of 1 % Codeine

Phosphate Powder, dissolve in water to make exactly 100
mL, then pipet exactly 10 mL of this solution, add exactly 10 mL of the internal standard solution and use this
solution as the test solution. Previously, weigh accurately
about 50 mg of Codeine Phosphate RS, separately determined the water content in the same manner as Codeine Phosphate Hydrate, dissolve in water to make exactly
100 mL, then pipet 10.0 mL of this solution, add exactly
10 mL of the internal standard solution and use this solu-
10% Codeine Phosphate Powder

10% Codeine Phosphate Powder contains not less than
9.3% and not more than 10.7% of codeine phosphate hydrate (C18H21NO3H3PO41/2H2O: 406.37).
Codeine Phosphate hydrate
100 g
Lactose
To make 1000 g

Identification Test Determine the absorption spectrum
of a solution of 10% Codeine Phosphate Powder (1 in
1000) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 283 nm and
287 nm.
Particle Size Distribution Test for preparations
quirement
It
It meets the re-
Assay Weigh accurately about 2.5 g of 10 % Codeine

Phosphate Powder, dissolve in water to make exactly 100
mL, then pipet 2.0 mL of this solution, add exactly 10
KP 9 249
20.0 mL and use this solution as the test solution. Separately, weigh accurately about 50 mg of Codeine Phosphate Hydrate RS, previously determined the water content in the same manner as Codeine Phosphate Hydrate,
dissolve in water to make exactly 100 mL, then pipet
10.0 mL of this solution, add exactly 10 mL of the internal standard solution and use this solution as the standard
Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS ,
of the peak area of codeine to that of the internal standard for the test solution and the standard solution, respectively.
(C18H21NO3H3PO41/2 H2O)
= amount (mg) of Codeine Phosphate Hydrate RS,
calculated on the anhydrous basis 1.0227
QT
5
QS
Internal standard solutionA solution of etilefline

about 40 C.
Mobile phase: Dissolve 1.0 g of sodium lauryl sulfate
in 500 mL of diluted phosphoric acid (1 in 1000) and adjust the pH to 3.0 with sodium hydroxide TS. To 240 mL
of this solution, add 70 mL of tetrahydrofuran and mix.
time of codeine is about 10 minutes.
System suitability
above operating conditions, codeine and the internal
standard are eluted in this order with the resolution between these peaks being not less than 4.0.
times with 20 L of the standard solution according to
the above operating conditions, the relative standard deviation of the ratios of the peak area of codeine to that of
the internal standard substance is not more than 1.0%.
Codeine Phosphate Tablets

Codeine Phosphate Tablets contains not less than 93.0%
and not more than 107.0% of labeled amount of codeine
phosphate hydrate (C18H21NO3H3PO41/2H2O: 406.37).
Method of Preparation Prepare as directed under Tablets, with Codeine Phosphate Hydrate.
Identification To a portion of powdered Codeine
Phosphate Tablets, equivalent to 0.1 g of Codeine Phosphate Hydrate according to the labeled amount, add 20
mL of water, shake and filter. To 2 mL of the filtrate, add
water to make 100 mL and determine the absorption
spectrum as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 283 nm
and 287 nm.
Codeine Phosphate Tablets. Weigh accurately a portion
of the powder, equivalent to about 0.1 g of codeine phosphate hydrate (C18H21NO3H3PO41/2H2O), add 30 mL of
water, shake, add 20 mL of diluted dilute sulfuric acid (1
in 20), treat the mixture with ultrasonic waves for 10 minutes, and add water to make exactly 100 mL. Filter the
solution, then pipet 5 mL of the filtrate, add exactly 10
20 mL, and use this solution as the test solution. Separately, weigh accurately about 50 mg of Codeine Phosphate Hydrate RS (previously determine the water in the
same manner as Codeine Phosphate Hydrate), dissolve in
water to make exactly 100 mL, then pipet 10 mL of this
solution, add exactly 10 mL of the internal standard solution, and use this solution as the standard solution. Perform the test with 20 L each of the sample solution and
standard solution as directed under Liquid Chromatography according to the following conditions, and calculate
the ratios, QT and QS , of the peak area of codeine to
that of the internal standard.

(C18H21NO3H3PO41/2H2O)
= WS QT 2 1.0227
QS
WS : Amount (mg) of Codeine Phosphate Hydrate RS,

Internal standard solution A solution of etilefline


the operating conditions in the Assay under 10% Codeine
Phosphate Powder.
Colchicine
CH3O
NHCOCH3
H
CH3O
CH3O
O
OCH3
C22H25NO6: 399.44
Colchicine, when dired, contains not less than 97.0% and
not more than 102.0% of colchicine (C22H25NO6), calculated on the anhydrous basis..
Description Colchicine is a yellowish white powder.
Colchine is very soluble in methanol, freely soluble in
dimethylformamide, in ethanol or in acetic anhydride
and sparingly soluble in water.
Colchicine is colored by light.
solutions of Colchicine and Colchicine RS in ethanol (1
in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities
absorption at the same wavelength.
(2) Add each 0.5 mL of solutions of Colchicine and
Colchicine RS in methanol (1 in 50) to 1 g of potassium
bromide for infrared absorption spectrum, grind thoroughly, dry in vacuum at 80 for 1 hour, determine the
absorption spectra of these powders as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
D : Between -235 and o
250 (0.1 g calculated on the anhydrous basis and corrected by the amount of ethyl acetate, ethanol, 10 mL,
100 mm)
Purity (1) Colchiceine Dissolve 0.1 g of Colchicine
in 10 mL of water and to 5 mL of this solution, add 2
drops of ferric chloride TS: no definite green color is
produced.
(2) Ethyl acetate and Chloroform Weigh accurately 0.6 g of Colchicine, dissolve in exactly 2 mL of internal standard solution, and add dimethylformamide to
Separately, weigh 0.3 g of chloroform using the 100 mLvolumetric flask containing about 20 mL of dimethylformamide, add dimethylformamide to make 100 mL.
Pipet exactly 2 mL of this solution, add dimethylformamide to make exactly 100 mL, and use this solution as
the standard solution (1). Separately weigh accurately
about 1.8 g of ethyl acetate, using the 100-mL volumetric
flask containing about 20 mL of dimethylformamide, add
dimethylformamide to make 100 mL. Pipet exactly 2 mL
of this solution, add exactly 2 mL of internal standard solution, add dimethylformamide to make 10 mL, and use
with each 2 L of the test solution, the standard solution
(1) and the standard solution (2), as directed under Gas
Chromatography according to the following conditions:
the peak area of chloroform obtained from the test solution is not more than the that obtained from the standard
solution (1). Determine the ratios of peak area, QT and
QS , of ethyl acetate to the peak area of the internal standard obtained from the test solution and the standard solution. Calculate the amount of ethyl acetate according to
the following equation: the amount of ethylacetate is not
more than 6.0%.
Amount (mg) of Ethyl acetate =
WS QT
2
W T QS
WS : amount (g) of Ethylacetate

WT : amount (g) of Colchicine
Internal standard solutionA solution of 1-propanol
in dimethylformamide (3 in 200).
Detector: A hydrogen flame ionized detector
Column: A fused glass column, about 0.53 mm in inside diameter and about 30 m in length, coated inside
surface with polyethylene glycol 20 M for gas chromatograph 1.0 m in thickness.
Column temperature: 60 C for 7 minutes then up to
100 C at a rate of 40 C per minute if necessary, and
hold at 100 C for 10 minutes.
Inject port temperature: A constant temperature of
about 130 C.
Detector temperature: A constant temperature of about
200 C.
Carrier gas: Helium
Flow rate: Adjust the folw rate so that the retention
time of ethylacetate is about 3 minutes.
Split ratio : about 1 : 20
System suitability
Test for required detactability: Pipet 2 mL of the
standard solution (2), and add dimethylformamide to
make exactly 25 mL. Pipet 1 mL of this solution, and add
dimethylformamide to make exactly 50 mL. Confirm
that the peak area of ethylacetate obtained from 2 L of
KP 9 251
this solution is equivalent to 0.11 and 0.21% of that obtained from 2L of the standard solution(2).
System performance: To 1 mL of chloroform add
dimethylformamide to make 10 mL. To 1 mL of this solution add 2 mL of ethylacetate, and dimethylformamide
to make 10 mL. To 2 mL of this solution add 2 mL of the
internal standard solution and dimethylformamide to
this solution according to the above operation conditions,
ethylacetate, chloroform and internal standard are eluted
in this order, with the resolution between chloroform and
internal standard being not less than 2.0.
times with 2 L of the standard solution (2) according to
the above operating conditions, the relative standard deviation of the ratio of peak area of ethylacetate to that of
the internal is not more than 3.0%.
(3) Related substancesDissolve 60 mg of Colchicine in 100 mL of diluted methanol (1 in 2). Pipet exactly
1 mL of this solution, add diluted methanol (1 in 2) to
make exactly 100 mL and use this solution as the test solution. Perform the test with 20 L of the test solution as
the following conditions. Determine each peak area of
the test solution by the automatic integration method and
calculate the total amount of the peaks other than colchicines by the area percentage method: not more than 5.0%.
Column: A stainless steel column,about 4.6 mm in
(1.0 m in particle diameter).
about 25 C.
Mobile phase: Add methanol to 450 mL of 0.05
mol/L potassium dihydrogen phosphate TS to make 1000
mL, Adjust pH to 5.5 with diluted phosphoric acid (7 in
200) .
System suitability
Test for required detactability: Pipet exactly 1 mL
of the test solution, and add diluted methanol (1 in 2) to
make exactly 50 mL. Conform that the peak area of colchicine obtained from 20 L of this solution is equivalent
to 1.4 to 2.6% of that obtained from colchicine of the test
solution.
with 20 L of the test solution according to the above
operating conditions, the number of theoretical plates is
6000, and the symmetry factor is not more than 1.5.
times with 20 L of the test solution according to the
above operation conditions, the relative standard deviation of the peak area of colchicine is not more than 2.0%.
as the retention time of colchicine beginning after the
peak of the solvent.

Water Not more than 2.0% (0.5 g, volumetric titration
method, back titration)
Assay Weigh accurately 0.4 g of Colchicine, previously dried, dissolve in 25 mL of acetic anhydride and titrate

= 19.972 mg of C22H25NO6
tight containers.
Colchicine Tablets
Colchicine Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of colchicine
(C22H25NO6: 399.44).
Preparation
Colchicine.
Prepare as directed under Tablets, with
Identification Weigh a portion of powdered Colchicine Tablets, equivalent to 20 mg of Colchicine, add 20

mL of water, allow the solids to settle and filter the supernatant liquid into a separatory funnel. Extract the filtrate with 30 mL of chloroform and evaporate the chloroform extract to dryness. Determine the infrared spectra of
the residue and Colchicine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Dissolution Test Perform the test with 1 tablet of Colchicine Tablets at 100 revolutions per minutes according
water as a dissolution solution. Filter through a membrane filter with pore size of not more than 0.8 m, after
30 minutes from the start of the test, pipet V mL of the
filtrate and extract with 15 mL of chloroform three times.
Evaporate the combined extracts to dryness, add chloroform to make exactly 10 mL and use this solution as the
Colchicine RS, previously dried at 105 C for 3 hours,
dissolve in dissolution solution, prepare the same concentration of solution as the test solution and use this solution as the standard solution. Determine the absorbance
of the test solution and the standard solution at 350 nm as
directed under the Ultraviolet-visible Spectrophotometry
using chloroform as a blank.
The dissolution rate of Colchicine Tablets in 30 minutes

Colchicine Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.6 mg of colchicine
(C22H25NO6), add a mixture of methanol and water (1 :
1), shake by mechanical means for 15 minutes, dilute
with the same mixture to make exactly 100 mL, filter and
use this solution as the test solution (prepared immediately prior to use). Separately, weigh accurately a portion of Colchicine RS, previously dried at 105 C for 3
hours, dissolve in a mixture of methanol and water (1 : 1)
and use this solution as the standard solution so that each
mL contains 6 g of Colchicine. Perform the test with 20
the following operating conditions. Determine the peak
areas, AT and AS , of colchicine of the test solution
Amounts (mg) of colchicine (C22H25NO6)

= 0 .1 C
AT
AS
C: Concentration (g/mL) of the standard solution.

Mobile phase: Add 45 mL of 0.5 mol/L potassium
dihydrogen phosphate and water to make 450 mL. Add
530 mL of methanol to this solution, cool to room temperature and dilute with methanol to make 1000 mL. Adjust pH to 5.5 0.05 with 0.5 mol/L phosphoric acid.
System suitability
with 20 L of the standard solution under the above operating conditions, the retention time of colchicine is between 5.5 and 9.5 minutes, and the number of theoretical
plates is not less than 4500.
above operating conditions, the relative standard deviation of the peak area of colchicine is not more than 2.0%.
tight containers.
Cortisone Acetate
O
O
H3C
O
H3C
CH2O
OH
CH3
C23H30O6: 402.48
Cortisone Acetate, when dried, contains not less than
97.0% and not more than 102.0% of cortisone acetate
(C23H30O6).
Description Cortisone Acetate is a white crystal or
Cortisone Acetate is sparingly soluble in methanol,
slightly soluble in dehydrated ethanol and practically insoluble in water.
Identification (1) Add 2 mL of sulfuric acid to 2 mg of
Cortisone Acetate and allow to stand for a while: a yellowish green color is produced and it gradually changes
to yellow-orange. Examine the solution under ultraviolet
light: the solution shows a pale green fluorescence. Add
carefully 10 mL of water to this solution: the yelloworange color of the solution is discharged and the solution remains clear.
(2) `Determine the absorption spectra of solutions of
Cortisone Acetate and Cortisone Acetate RS in methanol
(1 in 50000) as directed under the Ultraviolet-visible absorption Photometer: both spectra exhibit similar intensities of absorption at the same wavelengths..
(3) Determine the infrared spectra of Cortisone Acetate and Cortisone Acetate RS, previously dried, as directed in the potassium bromide disk method under the
intensities of absorption at the same wavenumbers. If any
difference appears between the spectra, dissolve Cortisone Acetate and Cortisone Acetate RS in acetone, respectively, evaporate the solutions to dryness and repeat
the test on the residues.
+2l6 (after drying, 0.1 g, 10 mL of methanol, 100 mm).
Purity Related substancesDissolve 25 mg of Cortisone Acetate in 10 mL of a mixture of acetonitrile, water
and glacial acetic acid (70 : 30 : 1) and use this solution
as the test solution. Pipet 1 mL of the test solution, add a
mixture of acetonitrile, water and glacial acetic acid (70 :
30 : 1) to make exactly 100 mL and use this solution as
the standard solution. Perform the test with each 15 L
KP 9 253
under the Liquid Chromatography according to the operating conditions. And determine each peak area according to the automatic integration method: the peak area
other than cortisone acetate obtained from the test solution is not greater than 1/2 times the peak area of cortisone acetate obtained from the standard solution. The
sum of peak area other than the peak area of cortisone
acetate obtained from the test solution is not greater than
1.5 times peak area of cortisone acetate obtained from
Detector: An ultraviolet-visible Photometer (wavelength: 254nm)
about 25 C.
mobile phase A and the mobile phase B as directed in the
following table
Mobile phase A : A mixture of water and acetonitrile
(7 : 3)
Mobile phase B : B mixture of acetonitrile and water
(7 : 3)
Time after injection
of sample (min)
0-5
5-25
25-30
Mobile phase
A (vol%)
90
9010
10
Mobile phase
B (vol %)
10
1090
90
Folw rate: About 1 mL per minute

System suitability
the standard solution add a mixture of acetonitrile, water
and glacial acetic acid (70 : 30 : 1) to make exactly 10
mL. Confirm that the peak area of cortisone acetate obtained with 15 L of this solution is equivalent to 8 to
12 % of that with 15 L of the standard solution
conditions, the number of theoretical plates and the
symmetry factor of the peak of cortisone acetate are not
less than 10,000 and not more than 1.3, respectively.
times with 15L of the standard solution under the above
the peak area of cortisone acetate is not more than 5.0 %.
the retention time of cortisone acetate beginning after the
solvent peak.
hours).

Assay Dissolve about 10 mg each of Cortisone Acetate
and Cortisone Acetate RS, previously dried and accurately weighed, in 50 mL of methanol, add exactly 5 mL
each of the internal standard solution, then add methanol
ratios, QT and QS , of the peak area of Cortisone Acetate to that of the internal standard, for the test solution
Amount (mg) of cortisone acetate (C23H30O6)

= amount (mg) of Cortisone Acetate RS QT
QS

about 25 C.
(13 : 7).
time of Cortisone Acetate is about 12 minutes.
System suitability
System performance: 10 mg of Cortisone Acetate
in 50 mL of methanol, add 5 mL of a solution of propylparahydroxybenzoate in methanol (3 in 5000) and add
methanol to make 100 mL. When the procedure is run
with 10 L of the standard solution under the above operating conditions, cortisone acetate and internal standard
sabstance are eluted in this order with the resolution between their peaks being not less than 4.0.
above operating conditions, the relative standard deviation of the ratios of peak area of cortisone acetate to that
of the internal standard is not more than 1.0%
tight containers.
Croconazole Hydrochloride
Cl
O
HCl
graphy. Spot 10 L each of the test solution and standard

mixture of ethyl acetate, hexane, methanol and ammonia
solution (30 : 15 : 5 : 1) to a distance of about 10 cm, and
spot and other than the spot of the starting point from the
test solution are not more than intense than the spot from
H2C
Loss on Drying Not more than 0.5 % (1.0 g, 60 C, 4

hours).
Residue on Ignition Not more than 0.1 % (1.0 g).
C18H15ClN2OHCl : 347.24
Croconazole Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of croconazole hydrochloride (C18H15ClN2OHCl).
Description Croconazole Hydrochloride is a white to
pale ellowish white crystalls or cryatalline powder.
Croconazole Hydrochloride is very soluble in water,
freely soluble in glacial acetic acid, in methanol or in
acetone, practically insoluble in ether.
solutions of Croconazole Hydrochloride and Croconazole Hydrochloride RS in methanol (1 in 20000) as directed under Ultraviolet-visible Spectrophotometry: both
same wavelengths.
of Croconazole Hydrochloride and Croconazole Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Dissolve about 50 mg of Croconazole Hydrochloride in 10 mL of water, add 2 mL of sodium hydroxide
TS and 20 mL of ether, and shake. Wash the separated
aqueous layer with two 10 mL portions of ether, and acidify the solution with 2 mL of dilute nitric acid: the solution responds to the qualitative tests for chloride.
Purity (1) Heavy metals - Proceed with 1.0 g of Croconazole Hydrochloride according to the method 4, and
(2) Related substances - Dissolve 50 mg of Croconazole Hydrochloride in 10 mL of methanol, and use this
solution as the test solution. Pipet 1 mL of the test solution, add methanol to make exactly 100 mL, and use this
these solutions as directed under Thin-layer Chromato-
Assay Weigh accurately about 0.6 g of Croconazole

glacial acetic acid, add 40 mL of acetic anhydride, and titrate with 0.1 mol/L perchloric acid VS [indicator: 1 to 2
drops of a solution of malachite green oxalate in glacial
acetic acid (1 in 100)] until the color of this solution
changes from blue-green through green to yellow-green.
Perform a blank determination, and make any necessary
correction.
1 mL of 0.1 mol/L perchloric acid

= 34.724 mg of C18H15ClN2OHCl
Packing and Storage Preserve in the well-closed, tight
containers.
Cyanamide
H2N
Aminonitrile
N
CH2N2: 42.04
Cyanamide contains not less than 97.0% and not more

than 101.0% of cyanamide (CH2N2), calculated on the
anhydrous basis.
Description Cyanamide is a white crystal or crystalline
powder and has a faint, characteristic odor.
Cyanamide is very soluble in water, in methanol or in
ethanol and freely soluble in ether.
Cyanamide is hygroscopic.
pHThe pH of a solution of 1.0 g of Cyanamide in
100 mL of water is between 5.0 and 6.5.
Identification (1) To 1 mL of a solution of Cyanamide
(1 in 100), add 1 mL of potassium naphthoquinone sulfonate TS and 0.2 mL of sodium hydroxide TS: a deep
red color develops.
(2) Drop one or two drops each of the solutions of
Cyanamide and Cyanimide RS in acetone (1 in 100) onto
KP 9 255
potassium bromide disks prepared as directed in the potassium bromide disk method under Infrared Sectrophotometry separately and air-dry the disks. Determine the
infrared spectra of the disks as directed in the film method under Infrared Spectrometry: both spectra exhibit
similar intensities of absorption at the same wave numbers.
O
H2N
H2N
C
C
CH2CH2
H2N
CH3
H2C

direct titration).
Assay Weigh accurately about 1 g of Cyanamide and
dissolve in water to make exactly 250 mL. Pipet exactly
15 mL of this solution, add 2 to 3 drops of dilute nitric
acid, 10 mL of ammonia TS and exactly 50 mL of 0.1
mol/L silver nitrate VS and allow to stand for 15 minutes
with occasional shaking. Add water to make exactly 100
mL, filter, discard the first 20 mL of the filtrate and pipet
the subsequent exactly 50 mL. After neutralizing this solution with dilute nitric acid, add 3 mL of dilute nitric acid and titrate the excess silver nitrate with 0.1 mol/L
ammonium thiocyanate VS (indicator: 2 mL of ferric
ammonium sulfate TS). Perform a blank determination

= 2.1020 mg of CH2N2
Packaging and Storage Preserve in a cold place, tight
containers.
Cyanocobalamin
H2C
NH2
O
C
NH2
CH2CH2
O
H2 C
H CH2CH2
H3C
CH3
CH3
H3 C
NH
CH2CH2
Co

1.0 g of Cyanamide in 10 mL of water: the solution is
(2) Heavy metalsProceed with 2.0 g of Cyanamide
NH2
CN
N
H3C
CH2
H
O CH3
O
CH3
CH3 O
CH3
CH3
OH
H
H
H
O
CH2OH
Vitamin B12
C63H88CoN14O14P: 1355.37
Cyanocobalamin contains not less than 96.0% and not

more
than
102.0%
of
cyanocobalamin
(C63H88CoN14O14P), calculated on the dried basis.
Description Cyanocobalamin is a dark red crystal or
powder.
Cyanocobalamin is sparingly soluble in water and
slightly soluble in ethanol
Cyanocobalamin is hygroscopic.
the test solution and the standard solution obtained in the
Assay, as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Mix 1 mg of Cyanocobalamin with 50 mg of potassium bisulfate and fuse by igniting. Cool, break up the
mass with a glass rod, add 3 mL of water and dissolve by
boiling. Add 1 drop of phenolphthalein TS, then add
drop-wise sodium hydroxide TS until a light red color
just develops. Add 0.5 g of sodium acetate, 0.5 mL of dilute acetic acid and 0.5 mL of a solution of disodium 1nitroso-2-naphthol-3,6-disulfonate (1 in 500): a red to
orange-red color is immediately produced. Then add 0.5
mL of hydrochloric acid and boil for 1 minute: the red
color does not disappear.
(3) Transfer 5 mg of Cyanocobalamin to a distilling
flask, dissolve in 5 mL of water and add 2.5 mL of hypophosphorous acid. Connect the flask with a short condenser and dip its tip into a test tube containing 1 mL of
a solution of sodium hydroxide (1 in 50). Heat gently for
10 minutes, then distill 1 mL into a test tube. To the test
tube, add 4 drops of a saturated solution of ferrous ammonium sulfate, shake gently, then add about 30 mg sodium fluoride and heat the contents to boil. Immediately
add drop-wise diluted sulfuric acid (1 in 7) until a clear
solution results, then add 3 to 5 drops more of diluted
sulfuric acid (1 in 7): a blue to blue-green color develops.
pH Dissolve 0.10 g of Cyanocobalamin in 20 mL of

freshly boiled and cooled water: the pH of this solution is
mg of Cyanocobalamin in 10 mL of water: the solution is
clear and red in color.
(2) PseudocyanocobalaminDissolve 1.0 mg of
Cyanocobalamin in 20 mL of water, transfer the solution
to a separator, add 5 mL of the mixture of m-cresol and
carbon tetrachloride (1 : 1) and shake vigorously for 1
minute. Allow to separate, draw off the lower layer into
another separator, add 5 mL of diluted sulfuric acid (1 in
7), shake vigorously and allow to separate completely, If
necessary, centrifuge the mixture: the supernatant liquid
is colorless or has no more color than the following control solution.
Control solutionDilute 0.6 mL of 0.02 mol/L potassium permanganate VS with water to make 1000 mL.
Loss on Drying Not more than 12% (50 mg, in vacuum at a pressure not exceeding 0.67 kPa, P2O5, 100 C,
4 hours).
Assay Weigh accurately about 20 mg each of Cyanocobalamin and Cyanocobalamin RS (previously determine the loss on drying in the same manner as Cyanocobalamin), dissolve in water to make exactly 1000 mL, respectively, and use these solutions as the test solution
and the standard solution. Determine the absorbances,
AT and AS , of the test solution and the standard solution, respectively, at 361 nm as directed under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of cyanocobalamin (C63H88CoN14O14P)

= amount (mg) of Cyanocobalamin RS,
calculated on the dried basis
tight containers.
AT
AS
Cyanocobalamin Injection
Vitamin B12 Injection
Cyanocobalamin Injection is an aqueous solution for injection.
Cyanocobalamin Injection contains not less than 95.0%
and not more than 115.0% of the labeled amount of cyanocobalamin (C63H88CoN14O14P: 1355.37)
red to red liquid.

Cyanocobalamin Injection is gradually colored by light.
Identification Determine the absorption spectrum of
the test solution obtained in the Assay as directed under
maxima between 277 nm and 279 nm, between 360 nm
and 362 nm, and between 548 nm and 552 nm. Determine the absorbances, A1 and A2 , of this solution at
the wavelengths of maximum absorption between 360
nm and 362 nm and between 548 nm and 552 nm, respectively: the ratio, A 2 / A1 is not less than 0.29 and
not more than 0.32.
Foreign Insoluble Matter Test It meets the requirement .
meets the requirement
It

Assay Measure exactly a volume of Cyanocobalamin
Injection, equivalent to about 2 mg of cyanocobalamin
(C63H88CoN14O14P), add water to make exactly 100 mL
weigh accurately about 20 mg of Cyanocobalamin RS
(previously determined the loss on drying in the same
manner as Cyanocobalamin), add water to make exactly
With these solutions, proceed as directed in the Assay
under Cyanocobalamin.
Amount (mg) of cyanocobalamin (C63H88Co N14O14P)

= amount (mg) of Cyanocobalamin RS,
calculated on the dried basis
AT
1
A S 10
Cyclopentolate Hydrochloride
OH
O
C
H
CH2
HCl
COCH2CH2N
CH3
Method of Preparation Prepare as directed under Injections, with Cyanocobalamin.
and enantiomer
Description Cyanocobalamin Injection is a clear, pale
C17H25NO3HCl: 327.85
KP 9 257
Cyclopentolate Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of cyclopentolate hydrochloride (C17H25NO3HCl).
Description Cyclopentolate Hydrochloride is a white,
crystalline powder and is odorless or has a characteristic
odor.
Cyclopentolate Hydrochloride is very soluble in water,
freely soluble in ethanol, in glacial acetic acid or in chloroform, sparingly soluble in acetic anhydride and practically insoluble in ether.
Identification (1) To 1 mL of a solution of Cyclopentolate Hydrochloride (1 in 100), add 1 mL of Reinecke
salt TS: a pale red precipitate is produced.
(2) Dissolve 0.2 g of Cyclopentolate Hydrochloride
in 2 mL of water, add 2 mL of sodium hydroxide TS and
boil for 1 minute. After cooling, add 2 drops of nitric acid: a phenylacetic acid-like odor is perceptible.
(3) Determine the infrared spectra of Cyclopentolate
Hydrochloride and Cyclopentolate Hydrochloride RS as
(4) A solution of Cyclopentolate Hydrochloride (1 in

hours).
Assay Weigh accurately about 0.5 g of Cyclopentolate
(4 : 1) and titrate with 0.1 mol/L perchloric acid VS until
the color of the solution changes from purple through
blue-green to yellow-green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination

Cyclophosphamide Hydrate
O
N
NH
pH Dissolve 0.20 g of Cyclopentolate Hydrochloride

in 20 ml of water: the pH of this solution is between 4.5
and 5.5.
Melting Point

g of Cyclopentolate Hydrochloride in 10 ml of water: the
(2) Heavy metalsProceed with 1.0 g of Cyclopentolate Hydrochloride according to Method 1 and perform
(3) Related substancesDissolve 0.20 g of Cyclopentolate Hydrochloride in 10 ml of chloroform and use
this solution as the test solution. Pipet exactly 1 mL of
the test solution and add chloroform to make exactly 20
mL. Pipet exactly 1 mL of this solution, add chloroform
to make exactly 10 mL and use this solution as the standard solution. Perform the test with the test solution and
the standard solution as directed under the Thin-layer
and the standard solution on a plate of silica gel for thinlayer chromatography. Develop the plate with a mixture
of isopropanol, n-butyl acetate, water and strong ammonia water (100 : 60 : 23 : 17) to a distance of about 10 cm
and air-dry the plate. Spray evenly a solution of sulfuric
acid in dehydrated ethanol (1 in 10) on the plate and heat
at 120 C for 30 minutes. Examine under ultraviolet light
CH2CH2Cl
H2O
CH2CH2Cl
C7H15Cl2N2O2PH2O: 279.10
Cyclophosphamide Hydrate contains not less than 97.0%
and not more than 101.0% of cyclophosphamide hydrate
(C7H15Cl2N2O2PH2O).
Description Cyclophosphamide Hydrate is a white
Cyclophosphamide Hydrate is very soluble in glacial
acetic acid, freely soluble in ethanol, acetic anhydride or
in chloroform and soluble in water or in ether.
Identification (1) Dissolve 0.1 g of Cyclophosphamide
Hydrate in 10 mL of water and add 5 mL of silver nitrate
TS: no precipitate is produced. Then boil this solution: a
white precipitate is produced. Collect the precipitate and
add dilute nitric acid to a portion of this precipitate: it
does not dissolve. Add excess ammonia TS to another
portion of the precipitate: it dissolves.
(2) Add 1 mL of diluted sulfuric acid (1 in 25) to 20
mg of Cyclophosphamide Hydrate and heat until white
fumes are evolved. After cooling, add 5 mL of water and
shake. Neutralize with ammonia TS, then acidify with dilute nitric acid: this solution responds to the Qualitative
Tests (2) for phosphate.
(3) Determine the infrared spectra of Cyclophosphamide Hydrate and Cyclophosphamide Hydrate RS as directed in the potassium bromide disk method under the

0.20 g of Cyclophosphamide Hydrate in 10 mL of water:
(2) ChloridePerform the test with 0.40 g of Cyclophosphamide Hydrate at a temperature not exceeding
20C. Prepare the control solution with 0.40 mL of 0.01
(3) Heavy metalsProceed with 1.0 g of Cyclophosphamide Hydrate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL of
Assay Weigh accurately about 0.3 g of Cyclophosphamide Hydrate, add 15 mL of hydrogen chloride-ethanol
TS and heat in a water-bath under a reflux condenser for
3.5 hours while protecting from moisture. Distill the
ethanol under reduced pressure. Dissolve the residue in
40 mL of a mixture of acetic anhydride and glacial acetic
acid (7 : 3) and titrate with 0.1 mol/L perchloric aciddioxane VS (indicator: 2 drops of methylrosaniline chloride TS) until the color of the solution changes from blue
through green to yellow. Perform a blank determination

= 13.955 mg of C7H15Cl2N2O2PH2O
Store at not exceeding 30 C.
Cyclophosphamide for Injection

Cyclophosphamide for Injection is a preparation for injection which is dissolved before use and Cyclophosphamide for Injection contains not less than 90.0% and
not more than 110.0% of the labeled amount of anhydrous cyclophosphamide (C7H15Cl2 N2O2P: 261.09).
Method of Preparation Prepare as directed under Injections, with Cyclophosphamide Hydrate and Sodium
Chloride.
Description Cyclophosphamide for Injection is a white
powder.
spectra of Cyclophosphamide for Injection and Cyclophosphamide Hydrate RS as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both exhibit the similar intensities of absoption at
(2) The retention time of the major peak in the chro-
matogram of the test solution under the Assay corresponds to that of the standard solution under the Assay.
pH Weigh accurately a portion of Cyclophosphamide
for Injection, equivalent to about 0.2 g of anhydrous
Cyclophosphamide and dissolve in 10 mL of water: pH
of the solution is between 3.0 and 9.0 (30 minutes after
preparation).
Cyclophosphamide.
10 Cyclophosphamide for Injections. Weigh accurately a
portion of Cyclophosphamide for Injection, equivalent to
0.10 g of anhydrous cyclophosphamide (C7H15Cl2N2O2P)
and proceed as directed in the Assay under Cyclophosphamide Tablets.
Packaging and Storage Preserve in not exceeding 30
C, hermetic containers. Not exceeding 25 C is recommended.
Cyclophosphamide Tablets
Cyclophosphamide Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of anhydrous cyclophosphamide (C7H15Cl2 N2O2P: 261.09).
Method of Preparation Prepare as directed under Tablets, with Cyclophosphamide Hydrate.
Identification (1) Weigh a quantity of powdered Cyclophosphamide Tablets, equivalent to 50 mg of Cyclophosphamide, extract with 25 mL of chloroform, then filter. To 2 mL of the filtrate, add 0.5 g of potassium bromide, mix, evaporate chloroform, carefully removing the
last trace of solvent in a small vacuum flask and use the
residue to prepare a potassium bromide disk. Determine
the infrared spectra of residue and Cyclophosphamide
Hydrate RS (previously dried) as directed in the potassium bromide disk method under the infrared Spectrophotometry and compare the spectra at wavenumbers between 700 cm-1 and 1600 cm-1: both spectra exhibit the
same intensities of absorption at the same wavenumbers.
(2) The retention time of the major peak in the chromatogram of the test solution under the Assay corresponds to that of the standard solution under the Assay.
KP 9 259
Place 1 Tablet in a volumetric flask of suitable size so
that the final concentration is about 500 g/mL. Fill the
flask about two-thirds full of water, shake until the Tablet
is completely disintegrated, and dilute with water to volume. Filter, discard the first 10 mL of the filtrate, and
use the remaining filtrate as the test solution. Separately,
dissolve an accurately weighed quantity of Cyclophosphamide Hydrate RS in water, and dilute with water to
obtain a solution having a known concentration of about
500 g/mL. Use this solution as the standard solution.
Place in separate test tubes 2.0 mL of the test solution,
2.0 mL of water (a blank), and 2.0 mL of the standard solution. Treat each tube as follows. Add 0.7 mL of perchloric acid solution, mix, and heat at 95 C for 10 minutes. Cool, add 1.0 mL of sodium acetate TS, mix, add
1.6 mL of 4-(p-nitrobenzyl)pyridine solution, mix, and
heat at 95 C for 10 minutes. Cool, add 8.0 mL of sodium hydroxide solution, and mix. Within 4 minutes, determine the absorbances of the solutions, as directed under the Ultraviolet-visible Spectrophotometry, at the wavelength of maximum absorbance at 560 nm, against the
blank. Determine the absorbances of the test solution and
the standard solution AT and As, respectively.
Amount (mg) of cyclophosphamide (C7H15Cl2N2O2P:
261.09) in the Tablet =
A
T
C T
500
AS
T: The labeled quanity (mg) of anhydrous cyclophosphamide in the Tablet

C: The concentration (g/mL) of cyclophosphamide
corrected based on Cyclophosphamide Hydrate RS
Cyclophosphamide Tablets. Weigh accurately a portion
of the powder, equivalent to 0.1 g of anhydrous cyclophosphamide (C7H15Cl2-N2O2P), add 50 mL of water,
shake, mix for 30 minutes and add water to make exactly
100 mL. Filter through a membrane filter, discard the
first 40 or 50 mL of the filtrate, pipet 25.0 mL of the filtrate, add 5.0 mL of internal standard solution and add
water to make exactly 50 mL and use this solution as the
test solution. Separately, weigh accurately 25 mg of Cyclophosphamide Hydrate RS (previously determine the
water content), dissolve in 25 mL of water, add 5.0 mL
of internal standard solution and water to make exactly
50 mL and use this solution as the standard solution. Perform the test with 25 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS, of the peak area of cyclophosphamide to that of the internal standard, for the test
Amount (mg) of cyclophosphamide (C7H15Cl2 N2O2P)

= amount (mg) of anhydrous cyclophosphamide in Cyc-
lophosphamide Hydrate RS QT 4
QS
Internal standard solutionWeigh 0.185 g of poxyethylbenzoate and dissolve in 250 mL of ethanol and
add water to make exactly 1000 mL.
(70 : 30).
System suitability
System performance: When the procedure is run with
25 L of the standard solution under the above operating
conditions, cyclophosphamide and internal standard are
eluted in this order with a resolution between their peaks
being not less than 2.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of cyclophosphamide
to that of internal standard is not more than 2.0%.
Packaging and Storage Preserve in not exceeding 30
C, tight containers.
Cyproheptadine Hydrochloride
Hydrate
HCl
1 1/2 H2O
N
CH 3
C21H21N.HCl.11/2 H2O: 350.88

Cyproheptadine Hydrochloride Hydrate, when dried,
of cyproheptadine hydrochloride (C21H21NHCl: 323.86).
Description Cyproheptadine Hydrochloride Hydrate is
a white to pale yellow, crystalline powder, is odorless
and has a slightly bitter taste.
Cyproheptadine Hydrochloride Hydrate is freely soluble
in methanol or in glacial acetic acid, soluble in chloro-

form, sparingly soluble in ethanol, slightly soluble in water and practically insoluble in ether.
Identification (1) Dissolve 0.1 g of Cyproheptadine
Hydrochloride Hydrate in 10 mL of methanol, apply 1
drop of this solution on filter paper, air-dry and examine
solution shows a pale blue fluorescence.
(2) Weigh 0.1 g of Cyproheptadine Hydrochloride
Hydrate, transfer to a separatory funnel, dissolve in 5 mL
of chloroform, add 4 mL of water and 1 mL of sodium
carbonate TS and shake. Transfer the chloroform layer to
another separatory funnel and wash with 4 mL of water
by shaking well. Filter the chloroform layer through absorbent cotton moistened previously with chloroform and
evaporate the filtrate to dryness. Dissolve the residue in 8
mL of dilute ethanol by warming at 65 C. Rub the inner
wall of the container with a glass rod while cooling until
crystallization begins and allow to stand for 30 minutes.
Collect the crystals and dry at 80 C for 2 hours: the
crystals melt between 111 C and 115 C.
(3) Determine absorption spectra of the solutions of
Cyproheptadine Hydrochloride Hydrate and Cyproheptadine Hydrochloride Hydrate RS, in ethanol (1 in
(4) A saturated solution of Cyproheptadine Hydrochloride Hydrate responds to the Qualitative Tests (2) for
chloride.
Purity (1) AcidDissolve 2.0 g of Cyproheptadine
Hydrochloride Hydrate in 25 mL of methanol and add 1
drop of methyl red TS and 0.30 mL of 0.1 mol/L sodium
hydroxide VS: a yellow color is observed.
(2) Heavy metals Proceed with 1.0 g of Cyproheptadine Hydrochloride Hydrate according to Method 2 and
Loss on Drying Between 7.0 and 9.0% (1g, in vacuum
Assay Weigh accurately about 0.5 g of Cyproheptadine
Hydrochloride Hydrate, previously dried, and dissolve in
20 ml of glacial acetic acid by warming at 50 C. After
cooling, add 40 ml of acetic anhydride and titrate with
Each ml of 0.1 mol/L perchloric acid VS

Cyproterone Acetate
O
CH3
CH3
O
CH3
H
CH3
H
O
H
H
O
Cl
C24H29ClO4 : 416.94
Cyproterone Acetate contains not less than 97.0% and
not more than 103.0% of cyproterone acetate
(C24H29ClO4), calculated on a dried basis.
Description Cyproterone Acetate is a white, crystalline
powder.
Cyproterone Acetate is very soluble in methylene chloride, freely soluble in acetone, soluble in methanol, sparingly soluble in ethanol, and practically insoluble in water
Identification (1) To about 1 mg of Cyproterone Acetate, add 2 mLof sulphuric acid and heat on a water-bath
for 2 min, and cool. Add the solution cautiously to 4 mL
of water and shake. The solution becomes violet.
(2) Determine the infrared absorption spectra of Cyproterone Acetate and Cyproterone Acetate RS as directed in the potassium bromide disk method under the
(3) Dissolve 20 mg of Cyproterone Acetate in methylene chloride to make 10 mL, and use this solution as the
test solution. Separately, dissolve 10 mg of Cyproterone
Acetate RS in methylene chloride to make 5 mL, and use
Chromatography. Spot 5 L each of the test solution and
the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography, develop
with a mixture of cyclohexane and ethyl acetate (50:50)
to a distance of about 15 cm, and dry the plate in air. Examine in ultraviolet light at 254 nm, and the principal
spot from the test solution and that from the standard solution show the same Rf value.
(4) Incinerate about 30 mg of Cyproterone Acetate
with 0.3 g of anhydrous sodium carbonate over a naked
flame for about 10 minutes. Cool, dissolve the residue in
5 mL of dilute nitric acid, and filter. To 1 mL of the filtrate, add 1 mL of water. The solution responds to the
Qualitative Tests (2) for chloride.
(5) In a test tube (about 180 mm 18 mm), place
about 15 mg of Cyproterone Acetate and 0.15 mL of
phosphoric acid. Close the tube with a stopper through
KP 9 261
which passes a small test tube (about 100 mm 10 mm)
containing water to act as a condenser. On the outside of
the smaller tube, hang a drop of 5% lanthanum nitrate solution. Place the apparatus in a water-bath for 5 minutes,
then take out the smaller tube. Remove the drop and mix
it with 0.05 mL of 0.01 mol/L iodine TS on a tile. Add at
the edge 0.05 mL of 2 mol/L ammonia. After 1 to 2 minutes, a blue color develops at the junction of the two
drops; the color intensifies and persists for a short time.
D : Between +152 to
+157 (0.25 g previously dried, acetone, 20 mL, 100
mm).
Purity Related substancesDissolve 10.0 mg of Cyproterone Acetate in acetonitrile to make exactly 10 mL,
and use this solution as the test solution. Dilute 1.0 mL
of the test solution to 100 mL with acetonitrile, and use
this solution as the standard solution (1). Dissolve 5 mg
of Medroxyprogesterone acetate RS in acetonitrile to
make exactly 50 mL. Dilute 1.0 mL of the solution to 10
mL with the standard solution (1), and use this solution
as the standard solution (2). Perform the test with 20 L
each of the test solution and the standard solutions as directed under the Liquid Chromatography according to
the following conditions. The sum of the areas of all the
peaks, other than the principal peak, from the test solution is not greater than 0.5 times the area of the principal
peak from the standard solution (1) (0.5%). Disregard
any peak with an area less than 0.05 times that of the
principal peak from the standard solution (1).
Column: A stainless steel column about 4.6 mm inside diameter and 12.5 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 m
(60:40).
System suitability
system so that the height of the principal peak from the
standard solution (1) is at least 50% of the full scale of
the recorder. When the procedure is run with the standard solution (2), the resolution between the peaks of cyproterone acetate and medroxyprogesterone acetate is not
less than 3.0.
Loss on Drying Not more than 0.5% (1 g, 80 C, not
exceeding 0.67 kPa, constant weight).
Assay Dissolve 50.0 mg of Cyproterone Acetate in methanol to make exactly 50 mL. Dilute 1.0 mL of the solu-
tion to 100 mL with methanol, and use this solution as

the test solution. Using methanol as the blank solution,
measure the absorbance (A) of the test solution at 282 nm.
Amount (mg) of cyproterone acetate (C24H29ClO4)
=
A
50000
414

L-Cystine
H
HOOC
NH2
S
S
H
COOH
NH2
C6H12N2O4S2: 240.30
L-Cystine, when dried, contains not less than 98.5% and
not more than 101.0% of L-cystine (C6H12N2O4S2).
Description L-Cystine is a white crystalline powder.

L-Cystine is practically insoluble in water or in ethanol.
L-Cystine dissolves in dilute sodium hydroxide TS.
Identification (1) Determine the infrared spectra of LCystine and L-Cystine RS in the potassium bromide disk
same wavenumbers.
(2) Examine the thin-layer chromatograms obtained
in the test for ninhydrin-positive substances under the
Purity (2): The principal spot from the test solution (2) is
same in color and Rf value the principal spot from the
(3) To 0.1 g of L-Cystine, add carefully 1 mL of
strong hydrogen peroxide TS and 0.1 mL of ferric chloride TS and allow to cool. Add 1 mL of dilute hydrochloric acid TS, 5 mL of water and 1 mL of barium chloride TS: a turbidity or a white precipitate develops within
3 minutes.
D : Between -218 and
224 (after drying, 0.5 g, 1 mol/L hydrochloric acid VS,
25 mL, 100 mm).
g of L-Cystine in 10 mL of dilute hydrochloric acid TS:
The solution is clear and not more intensely colored than
Color Matching Solution F.
(2) Ninhydrin-positive substancesDissolve 0.1 g

of L-Cystine in 10 mL of 1 mol/L hydrochloric acid VS
and use this solution as the test solution (1). Pipet 1.0 mL
of the test solution, add water to make 50.0 mL and use
this solution as the test solution (2). Separately, dissolve
10 mg of L-Cystine RS in 1 mL of 1 mol/L hydrochloric
acid VS, add water to make 50 mL and use this solution
as the standard solution (1). To 2 mL of the test solution
(2) add water to make 20 mL and use this solution as the
standard solution (2). Dissolve 10 mg of L-Cystine RS
and 10 mg of arginine hydrochloride in 1 mL of 1 mol/L
hydrochloric acid VS, add water to make 25 mL and use
Chromatography. Spot 5 L each of the test solution (1),
the test solution (2), the standard solution (1), the standard solution (2) and the standard solution (3) on a plate
plates with an upper layer of a mixture of concentrated
ammonia water and 2-propanol (30 : 70) to a distance of
about 15 cm and air-dry the plates. Spray evenly with a
solution of ninhydrin VS on plate and heat at 100 C to
150 C for 15 minutes: the spots other than principal spot
from the test solution (1) are not more intense than the
spot from the standard solution (2) and the chromatogram obtained from the standard solution (3) shows two
clearly separated spots.
(3) ChloridePerform the test with 0.50 g of LCystine. Prepare the control solution with 0.29 mL of
(4) SulfateDissolve 0.50 g of L-Cystine in 5 mL of
dilute hydrochloric acid TS, add water to make 15 mL
and use this solution as the test solution. Prepare the control solution with 0.32 mL of 0.005 mol/L sulfuric acid
VS, 5 mL of dilute hydrochloric acid TS and add water
to make 15 mL (not more than 0.030%).
(5) AmmoniumPerform the test with 0.25 g of LCystine. Prepare the control solution with 5.0 mL of
standard ammonium solution (not more than 0.020%).
(6) Heavy metalsProceed with 2.0 g of L-Cystine
(7) IronDissolve 1.0 g of L-Cystine in 10 mL of dilute hydrochloric acid TS in a separator, extract with
three quantities, each 10 mL of methyl isobutyl ketone.
To the methyl isobutyl ketone layer add 10 mL of water
and mix with shaking for 3 minutes. Take the water layer,
add 30 mL of acetic acid-sodium acetate buffer solution,
pH 4.5 and use this solution as the test solution. Perform
the test with the test solution according to Method B.
Prepare the control solution with 1.0 mL of standard iron
Loss on Drying Not more than 0.5% (1 g, 105C, constant mass)
Assay Weigh accurately about 0.1 g of L-Cystine, previously dried, transfer to a capped flask and dissolve in 2
mL of dilute sodium hydroxide VS and 10 mL of water.
Add 10 mL of potassium bromide solution (2 in 10), 50.0
mL of 1/60 mol/L potassium bromate VS and 15 mL of
dilute hydrochloric acid TS. Stopper the flask and cool in
iced water. Allow to stand in the dark for 10 minutes and
add 1.5 g of potassium iodide. After 1 minute, titrate with
0.1 mol/L sodium thiosulfate (indicator: 2 mL of starch
TS). Perform a blank determination and make any necessary correction.
Each mL of 1/60 mol/L solution of potassium

bromate VS = 2.4030 mg of C6H12N2O4S2

Cytarabine
NH2
O
HOH2C
O
H
HO
H
OH
C9H13N3O5: 243.22
Cytarabine, when dried, contains not less than 98.5% and
not more than 101.0% of cytarabine (C9H13N3O5).
Description Cytarabine is a white crystals or crystalline powder.
Cytarabine is freely soluble in water, soluble in glacial
acetic acid, very slightly soluble in ethanol and practically insoluble in ether.
Identification (1) To 1 mL of a solution of Cytarabine
(1 in 1000), add 1 drop of bromine TS, allow to stand for
10 minutes and expel the excess bromine under a current
of air. To this solution, add 1 mL of a solution of ascorbic
acid (1 in 5000) and 1 mL of ninhydrin TS and heat in a
water-bath for 30 minutes: a purple color develops.
(2) To 1 mL of a solution of Cytarabine (1 in 100),
add 1 mL of orcin-ferric chloride TS and heat in a waterbath for 30 minutes: a green color develops.
1%
Absorbance E1cm
(282 nm): Between 530 and 570 (after drying, 2 mg, 0.1 mol/L hydrochloric acid TS, 200
mL).

+160 (after drying, 0.1 g, water, 10 mL, 100 mm).
KP 9 263
pH Dissolve 0.20 g of Cytarabine in 20 mL of water:

g of Cytarabine in 10 mL of water: the solution is clear
and colorless.
(2) ChloridePerform the test with 1.0 g of Cytarabine. Prepare the control solution with 0.25 mL of 0.01
(3) Heavy metalsProceed with 1.0 g of Cytarabine
Cytarabine according to Method 3 and perform the test
(5) Related substancesDissolve 0.10 g of Cytarabine in 10 mL of water and use this solution as the test
solution. Pipet exactly 1 mL of the test solution, add water to make exactly 200 mL and use this solution as the
and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with n-butanol saturated with water to a distance of about 12 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot
Spray evenly acidic potassium permanganate TS on the
plate: any spot other than the principal spot does not appear.
Assay Weigh accurately about 0.2 g of Cytarabine,
and titrate with 0.05 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination and make any necessary correction.

= 12.161 mg of C9H13N3O5
Cytarabine for Injection

Cytarabine for Injection is a preparation for injection
which is dissolved before use. Cytarabine for Injection
of the labeled amount of cytarabine (C9H13N3O5: 243.22).
Method of Preparation Prepare as directed under Injections, with cytarabine.
Identification The retention time of the major peak in
the chromatogram of the test solution under the Assay
corresponds to that in the chromatogram of the standard
solution under the Assay.
pH Between 4.0 and 6.0 (water, 20 mg/mL).
Cytarabine.
direct titration).
Assay Take 10 Cytarabine for Injection, dissolve in
water to make a solution containing 10 mg of cytarabine
(C9H13N3O5) per mL. Pipet 5.0 mL of this solution and
add water to make exactly 50 mL. Pipet 3.0 mL of this
solution, add 5.0 mL of the internal standard solution and
mobile phase to make exactly 25 mL and use this solution as the test solution. Separately, weigh accurately 50
mg of Cytarabine RS (previously dried at 60 C, not
more than 0.67 kPa, for 3 hours), dissolve in water to
make exactly 50 mL. Pipet 3.0 mL of this solution and
add 5.0 mL of the internal standard solutio and mobile
the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of
the peak area of Cytarabine to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of cytarabine (C9H13N3O5)

= amount (mg) of Cytarabine RS QT 1
QS
Internal standard solution0.14% p-toluenic acid

in methanol.
Column: A stainless steel column, 4 mm to 4.6 mm in
inside diameter and 25 cm to 30 cm in length, packed
with octadecylsilanized silica gel for liquid chromatography (5 m to 10 m in particle diameter).
Mobile phase: Dissolve 0.69 g of sodium dihydro-

phosphate and 1.34 g of sodium monophosphate in 950
mL of water. Add 50 mL of methanol and mix.
System suitability
System performance: Weigh a sufficient portion of
Uracylarabinoside RS and Cytarabine RS, dissolve in
water to make a solution containing 10 g and 600 g
per 1 mL, respectively, dilute with same volume of internal standard solution, mix with about four times volume
of mobile phase. When the procedure is run with 10 L
of this solution under the above operating condition, cytarabine, uracylarabinoside and p-toluenic acid are eluted
in this order with a resolution between cytarabine and
uracylarabinoside peaks being not less than 2.5.
above operating conditions, the relative standard deviation of the ratios of the peak area of cytarabine to that of
Dantrolene Sodium Hydrate

O
O
O 2N
NNa
H
C
3 1/2 H2O
N
O
C14H9N4NaO531/2 H2O: 399.29

Dantrolene Sodium contains not less than 98.0% and not
more than 101.0% of dantrolene sodium (C14H9-N4
NaO5), calculated on the anhydrous basis.
Description Dantrolene Sodium Hydrate is a yellowish
orange to deep orange, crystalline powder.
Dantrolene Sodium Hydrate is soluble in propylene glycol, sparingly soluble in methanol, slightly soluble in
ethanol, very slightly soluble in water or in glacial acetic
acid and practically insoluble in acetone, in tetrahydrofuran or in ether.
solutions of Dantrolene Sodium Hydrate and Dantrolene
Sodium Hydrate RS in methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Dantrolene Sodium Hydrate and Dantrolene Sodium Hydrate RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry: both exhibit similar intensity of absorption at the same wavenumbers.
(3) To 0.1 g of Dantrolene Sodium Hydrate, add 20
mL of water and 2 drops of glacial acetic acid, shake

well and filter: the filtrate responds to the Qualitative
Tests (1) for sodium salt.
Purity (1) AlkaliTo about 0.7 g of Dantrolene Sodium Hydrate, add 10 mL of water, shake well and centrifuge or filter through a membrane filter. To 5 mL of
the supernatant or the filtrate, add 45 mL of water, 3
drops of phenophthalein TS and 0.10 mL of 0.1 mol/L
hydrochloric acid VS: a red color is not observed.
(2) Heavy metalsProceed with 1.0 g of Dantrolene
Sodium Hydrate according to Method 2 and perform the
(3) Related substancesDissolve 50.0 mg of Dantrolene Sodium Hydrate in 20 mL of tetrahydrofuran and
2 mL of glacial acetic acid, add dehydrated ethanol to
make exactly 100 mL and use this solution as the test solution. Pipet 1.0 mL of the test solution, add dehydrated
under the Liquid Chromatography according to the following conditions. Determine each peak area from the
test solution and the standard solution by the automatic
integration method: the total area of all peaks other than
the peak of dantrolene from the test solution is not larger
than the peak area of dantrolene from the standard solution.
Detector : An ultraviolet absorption photometer (wavelength: 300 nm).
Column : A stainless steel column, 4 m in inside diameter and about 15 cm in length, packed with silica gel
for liquid chromatography (5 m in particle diameter).
Column temperature : A constant temperature of
about 30 C.
Mobile phase: A mixture of hexane, glacial acetic acid and dehydrated ethanol (90 : 10 : 9).
Flow rate : Adjust the flow rate so that the retention
time of dantrolene is about 8 minutes.
System suitability
System performance: Dissolve 5 mg of Dantrolene
Sodium Hydrate and 0.1 g of theophylline in 20 mL of
tetrahydrofuran and 2 mL of glacial acetic acid and add
dehydrated ethanol to make 100 mL. To 10 mL of this
solution, add dehydrated ethanol to make 100 mL and
use this solution as the standard solution. When the procedure is run with 10 L of the standard solution under
the above operating conditions, theophylline and dantrolene are eluted in this order with the resolution between
their peaks being not less than 6.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of dantrolene from 10 L of
the standard solution is 10% to 40% of the full scale.
the retention time of Dantrolene after the solvent peak.
KP 9 265
Assay Weigh accurately 0.7 g of Dantrolene Sodium
Hydrate, dissolve in 180 mL of a mixture of propylene
glycol and acetone (1 : 1) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 33.624 mg of C14H9N4NaO5
Dapsone
O
O
S
H2N
D.D.S
NH2
C12H12N2O2S: 248.30
Dapsone contains not less than 98.0% and not more than
102.0% of dapsone (C12H12N2O2S), calculated on the anhydrous basis.
Description Dapsone is a white or pale yellow crystalline powder.
Dapsone is freely soluble in acetone, slightly soluble in
ethanol and practically insoluble in water.
Dapsone dissolves in dilute inorganic acid,
solutions of Dapsone and Dapsone RS in methanol (1 in
(2) Dry a suitable amount of Dapsone and Dapsone
RS and measure the infrared spectra as directed in the
potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibits similar intensities of
Melting Point
Purity (1) SeleniumAdd 0.5 mL of a mixture containing perchloric acid and sulfuric acid (1 : 1), 2 mL of
nitric acid to about 0.10 g of Dapsone and heat in a steam
bath. Cool the solution until a brown gas is not evolved
and the solution becomes clear with an evanescent yellowish color. Then, add 4 mL of nitric acid and water to
make exactly 50 mL. Use this solution as the test solution. Separately, pipet 3 mL of selenium standard solution, add 0.5 mL of a mixture containing perchloric acid
and sulfuric acid (1 : 1), 6 mL of nitric acid and water to
make exactly 50 mL. Use this solution as the standard
solution. Perform the test on the standard and the test solution as directed under the Atomic Absorption Spectrophotometry. Measure the absorbance AT for the test solution and AS for the standard solution when the reading of
the display rapidly rises and, then, reaches a plateau. AT
is less than AS (not more than 30 ppm). This test is performed using a hydride generator and a heating cell.
Atomizing temperature : When an electric furnace is
used, the temperature is set at about 1000 C.
Carrier gas: Nitrogen or argon
Lamp : Selenium hollow-cathode lamp
Wavelength : 196.0 nm
(2) Related substancesDissolve 0.50 g of Dapsone
in 50.0 mL of methanol and use this solution as the test

solution. Pipet 1.0 mL of this solution accurately and add
as the standard solution (1). Pipet 10.0 mL of the standard solution (1), add methanol to make exactly 50 mL
and use this as the standard solution (2). Perform the test
with the test solution and the standard solutions (1) and
(2) as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution and the standard solutions (1) and (2) on a plate of silica gel for thin-layer
ethylacetate, n-heptane, methanol and 13.5 mol/L of
ammonia reagent mixture (20 : 20 : 6 : 1) and air-dry the
plate. Spray evenly 0.1% 4-dimethylaminocinnam aldehyde solution of hydrochloric acid and ethanol mixture
(1 : 99) on the plate: the spot having a strong intensity
second to the principal spot from the test solution is not
more intense than that from the standard solution (1).
The spots other than the above two spots from the test
solution are not more intense than that from the standard
solution (2).
hours).
Assay
Weigh accurately about 50 mg of Dapsone,
dissolve in methanol to make exactly 200 mL. Pipet 5
mL of the solution, add methanol to make exactly 50 mL
weigh accurately about 50 mg of Dapsone RS, diluted
similarly to the test solution with methanol and use this
10 L each of the test and standard solution as directed
under the Liquid Chromatography. Determine each peak
area, AT and AS , of Dapsone for the test solution and
Amount (mg) of dapsone (C12H12N2O2S)

= Amount (mg) of Dapsone RS
AT
AS
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with
porous silica for liquid chromatography (10 m in particle diameter).
Mobile phase: Mix 100 mL of isopropanol, 100 mL
of ethylacetate, 100 mL of acetonitrile and pentane to
make 1000 mL. Allow the mixture to cool to room temperature.
System suitability
KP 9 267
above operating conditions, the relative standard deviation of the peak area of dapsone is not more than 2.0 %.

Daunorubicin Hydrochloride
OH
Histamine It meets the requirement, when Daunorubicin Hydrochloride is used in a sterile preparation,. Weigh
appropriate amount of Daunorubicin Hydrochloride, dissolve in water, make the solution so that each mL contains 5.0 mg, and use the solution as the test solution.
O
CH3
OH
OH
H3C
HCl
H3C
Pyrogen Test It meets the requirement, when Daunorubicin Hydrochloride is used in a sterile preparation.
Weigh appropriate amount of Daunorubicin Hydrochloride, dissolve in water, make the solution so that each mL
contains 2.0 mg, and use the solution as the test solution.
The amount of injection is 1.0 mL of the test solution per
kg of body weight of rabbit.
O
NH2
OH
C27H29NO10HCl: 563.98
Daunorubicin Hydrochloride is the hydrochloride of an

anthracycline substance having antitumor activity produced by the growth of Streptomyces peucetius.
Daunorubicin Hydrochloride contains not less than 900
g (potency) per mg of daunoarubicin hydrochloride
(C27H29NO10HCl), calculated on the dried basis.
Description Daunorubicin Hydrochloride is a red
powder.
Daunorubicin Hydrochloride is very soluble in water and
in methanol, slightly soluble in ethanol, and practically
insoluble in ether.
Identification (1) Dissolve 1 ~ 2 mg of Daunorubicin
Hydrochloride in 5 mL of 1 mol/L sodium hydroxide: a
blue-purple color develops.
of Daunorubicin Hydrochloride and Daunorubicin Hydrochloride RS in methanol (1 in 100000), as directed
under Ultraviolet-visible Spectrophotometry, both spectra exhibit similar intensities of absorption at the same
wavelengths.
D : +250 ~ +275 (15
mg calculated on the dried basis, methanol, 10 mL, 100
mm).
1%
Absorbance E1 cm (495 nm): 210 ~ 250 (10 mg calculated on the dried basis, methanol, 500 mL).
of Daunorubicin Hydrochloride in 10 mL of water is between 4.5 and 6.5.
Sterility Test It meets the requirement, when Daunorubicin Hydrochloride is used in a sterile preparation,.

Assay Weigh accurately an amount of Daunorubicin
Hydrochloride and Daunorubicin Hydrochloride RS,
equivalent to about 25 mg (potency), dissolve each in a
suitable amount of the mobile phase, add exactly 4 mL of
the internal standard solution and the mobile phase to
make 20 mL, and use these solutions as the test solution
with 5 L of each of the test solution and the standard
according to the following operating conditions, and determine the ratios, QT and QS , of the peak area of
daunorubicin to that of the internal standard..
Amount [g (potency)] of Daunorubicin hydrochloride

(C27H29NO10HCl)
= Amount [g (potency)] of Daunorubicin hydrochloride
RS
QT
QS
Internal standard solutionA solution of 2naphthalenesulfonic acid in the mobile phase (1 in 100)
Column: A stainless steel column, about 4 mm in inside
diameter and about 300 mm in length, packed with octadecylsilanized silica gel for liquid chromatography (10
Mobile phase: Adjust the pH of a mixture of water and
acetonitrile (62:38) to 2.2 0.2 with phosphoric acid
time of daunorubicin is about 9 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, the internal standard and daunorubicin

times with 5 L of the standard solution under the operating conditions, the relative standard deviation of the ratios of the peak area of daunorubicin to that of the internal standard is not more than 2.0 %.
Deferoxamine Mesilate
O
H2N(H2C)5N
OH
O
CH2CH2
O
NH(CH2)5N
OH
O
CH2CH2
O
NH(CH2)5N
CH2
CH3SO3H
OH
C25H48N6O8CH4O3S: 656.79
Deferoxamine Mesilate contains not less than 98.0% and
not more than 102.0% of deferoxamine mesilate
(C25H48N6O8CH4O3S), calculated on the anhydrous basis.
Description Deferoxamine Mesilate is a white to pale
yellow white, crystalline powder.
Deferoxamine Mesilate is freely soluble in water and
practically insoluble in dehydrated ethanol, in isopropanol or in ether.
Identification (1) To 5 mL of a solution of Deferoxamine Mesilate (1 in 500), add 1 drop of ferric chloride
TS: a deep red color is observed.
(2) To 50 mg of Deferoxamine Mesilate, add 0.2 g of
sodium hydroxide, melt by heating over a small flame
and heat further for 2 to 3 seconds. To the residue, add
0.5 mL of water, acidify with dilute hydrochloric acid
and warm: the gas evolved changes moistened potassium
iodate-starch paper to blue.
(3) Determine the infrared spectra of Deferoxamine
Mesilate and Deferoxamine Mesilate RS as directed in
Spectrophotometry: both exhibit similar intensities of absorption at the same wavenumbers.
pH Dissolve 1.0 g of Deferoxamine Mesilate in 10 mL
g of Deferoxamine Mesilate in 10 mL of water: the solution is clear and colorless to pale yellow.
(2) ChloridePerform the test with 1.0 g of Deferoxamine Mesilate. Prepare the control solution with
than 0.032%).
(3) SulfatePerform the test with 0.6 g of Deferoxamine Mesilate. Prepare the control solution with 0.50
0.040%).
(4) Heavy metalsProceed with 2.0 g of Deferoxamine Mesilate according to Method 4 and perform the
Deferoxamine Mesilate according to Method 3 and perform the test. Use a solution of magnesium nitrate in
(6) Related substancesDissolve 50.0 mg of Deferoxamine Mesilate in 50.0 mL of the mobile phase and
standard solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area of the test solution and the standard
solution by the automatic integration method: the total
area of all peaks other than the peak of deferoxamine
from the test solution is not larger than the peak area of
deferoxamine from the standard solution.
about 40 C.
Mobile phase: Dissolve 1.32 g of dibasic ammonium
phosphate, 0.37 g of disodium ethylenediaminetetraacetate and 1.08 g of sodium 1-heptanesulfonate in 950 mL
of water. Adjust pH of this solution with phosphoric acid
to 2.8 and add 100 mL of isopropanol to 800 mL of this
solution.
time of deferoxamine is about 15 minutes.
System suitability
System performance: Dissolve 16 mg of Deferoxamine Mesilate and 4 mg of methylparahydroxybenzoate
in 50 mL of the mobile phase. When the procedure is run
conditions, deferoxamine and methyl p-hydroxybenzoate
so that the peak height of deferoxamine from 20 L of
the retention time of deferoxamine after the solvent peak.
direct titration).
Assay Weigh accurately about 60 mg of Deferoxamine
KP 9 269
Mesilate and Deferoxamine Mesilate RS (determine the
content of water before using in the same manner as Deferoxamine Mesilate), dissolve each in 20 mL of water,
add 10 mL of 0.05 mol/L sulfuric acid TS and add water
to make exactly 50 mL. Pipet 5.0 mL each of these solutions, add exactly 5 mL of 0.05 mol/L sulfuric acid TS
and exactly 0.2 mL of ferric chloride TS, then add water
to make exactly 50 mL and use these solutions as the test
solution and the standard solution, respectively. Perform
directed under the Spectrophotometry, using a solution
prepared by adding 0.05 mol/L sulfuric acid TS to 0.2
mL of ferric chloride TS to make exactly 50 mL as the
blank and determine the absorbances, AT and AS, for the
430 nm.
Amount (mg) of deferoxamine mesilate
(C25H48N6O8CH4O3S)
= amount (mg) of Deferoxamine Mesilate RS,
A
calculated on the anhydrous basis T
AS
Dehydrocholic Acid
H
O
H3C
CH3
CH3
H
O
CO2H
H
O
C24H34O5: 402.52
Dehydrocholic Acid, when dried, contains not less than
98.5% and not more than 101.0% of dehydrocholic acid
(C24H34O5).
Description Dehydrocholic Acid is a white crystalline
powder, is odorless and has a bitter taste.
Dehydrocholic Acid is sparingly soluble in dioxane,
water or in ether.
Dehydrocholic Acid dissolves in sodium hydroxide TS.
Identification (1) Dissolve 5 mg of Dehydrocholic Acid in 1 mL of sulfuric acid and 1 drop of formalin, allow
to stand for 5 minutes and add 5 mL of water: the solution shows a yellow color and a blue-green fluorescence.
(2) To 20 mg of Dehydrocholic Acid, add 1 mL of
ethanol, shake, add 5 drops of m-dinitrobezene TS and
0.5 mL of a solution of sodium hydroxide (1 in 8) and allow to stand: a purple to red-purple color is observed and
gradually changes to brown.

D : Between +29 and
Melting Point
Purity (1) OdorTo 2.0 g of Dehydrocholic Acid, add

100 mL of water and boil for 2 minutes: the solution is
odorless.
(2) Clarity and color of solutionTo 0.10 g of Dehydrocholic Acid, previously powdered, add 30 mL of
ethanol and dissolve by shaking for 10 minutes: the solution is clear and colorless.
(3) ChlorideTo 2.0 g of Dehydrocholic Acid, add
100 mL of water, shake for 5 minutes and filter. Take 25
mL of the this solution, add 6 mL of dilute nitric acid,
heat in a water-bath for 6 minutes, filter after cooling and
collect the clear filtrate. Wash the residue with 10 mL of
water, combine the washings and the filtrate, dilute with
water to make 50 mL and perform the test using this solution as the test solution. Prepare the control solution
more than 0.021%).
(4) SulfateAdd 1 mL of dilute hydrochloric acid to
25 mL of the test solution obtained in (3), heat in a water-bath for 6 minutes, filter after cooling and collect the
clear filtrate. Wash the residue with 10 mL of water,
combine the washings and the filtrate, dilute with water
to make 50 mL and perform the test using this solution as
0.048%).
(5) Heavy metalsProceed with 1.0 g of Dehydrocholic Acid according to Method 2 and perform the test.
(6) BariumTo the solution obtained in (1), add 2
mL of hydrochloric acid and boil for 2 minutes. Cool, filter and wash with water until 100 mL of the filtrate is obtained. To 10 mL of the filtrate, add 1 mL of dilute sulfuric acid: no turbidity is produced.
hours).
Assay Weigh accurately about 0.5 g of Dehydrocholic
Acid, previously dried, add 40 mL of neutralized ethanol
and 20 mL of water and dissolve by warming. Add 2
drops of phenolphthalein TS, titrate with 0.1 mol/L sodium hydroxide VS, add 100 mL of freshly boiled and
cooled water as the end point is approached and continue
the titration.

= 40.25 mg of C24H34O5
Dehydrocholic Acid Injection

Sodium Dehydrocholate Injection
Purified Dehydrocholic Acid

H
O
H3C
CH3
CH3
H
O
CO2H
Dehydrocholic Acid Injection is an aqueous solution for

injection.
Dehydrocholic Acid Injection contains not less than
of dehydrocholic acid (C24H34O5: 402.52).
Method of Preparation Dissolve Purified Dehydrocholic Acid in a solution of Sodium Hydroxide and prepare as directed under Injections.
H
O
C24H34O5: 402.52
Purified Dehydrocholic Acid, when dried, contains not
less than 99.0% and not more than 101.0% of dehydrocholic acid (C24H34O5: 402.52).
Description Purified Dehydrocholic Acid is a white
Purified Dehydrocholic Acid is sparingly soluble in dioxane, slightly soluble in ethanol and practically insoluble
in water or in ether.
Purified Dehydrocholic Acid dissolves in sodium hydroxide TS.
Identification Purified Dehydrocholic Acid responds
to the Identification for Dehydrocholic Acid.
D : Between +29 and
Purity Purified Dehydrocholic Acid responds to the
Purity for Dehydrocholic Acid.
hours).
Description Dehydrocholic Acid Injection is a clear,

colorless to pale yellow liquid and has a bitter taste.
pHBetween 9 and 11.
Identification Transfer a volume of Dehydrocholic Acid Injection, equivalent to 0.1 g of Purified Dehydrocholic Acid according to the labeled amount, to a separator
and add 10 mL of water and 1 mL of dilute hydrochloric
acid: a white precipitate is produced. Extract the mixture
with three 15 mL volumes of chloroform, combine all of
the chloroform extracts, evaporate the chloroform on a
water-bath and dry the residue at 105 C for 1 hour: the
residue so obtained melts between 235 C and 242 C.
Purity Heavy metalsEvaporate a volume of Dehydrocholic Acid Injection, equivalent to 1.0 g of Purified
Dehydrocholic Acid according to the labeled amount, on
a water-bath to dryness. Proceed with the residue according to Method 2 and perform the test. Prepare the control
than 20 ppm).
Dehydrocholic Acid.

Assay Purified Dehydrocholic Acid responds to the
Assay for Dehydrocholic Acid.

= 40.25 mg of C24H34O5

It

Assay Weigh exactly a volume of Dehydrocholic Acid
Injection, equivalent to about 0.5 g of dehydrocholic acid
(C24H34O5) and add methanol to make exactly 50 mL.
Pipet 5.0 mL of this solution and add 8.0 mL of the internal standard solution. Then add methanol to make exactly 50 mL and use this solution as the test solution.
KP 9 271
Separately weigh accurately 50 mg of Dehydrocholic Acid RS, previously dried, add 8.0 mL of the internal standard solution, add methanol to make exactly 50 mL and
ratios, QT and QS , of the peak area of dehydrocholic
acid of the test solution and the standard solution to that
of the internal standard, respectively.
Deslanoside
O
O
HO
H
CH3
Amount (mg) of dehydrocholic acid (C24H34O5)

= amount (mg) of Dehydrocholic Acid RS QT
QS

hermetic containers. Colored containers may be used.
OH
O
H
H
H
CH3
10
Internal standard solutionA methanol solution of

butyl parahydroxybenzoate (3 in 3200).
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography
(5m to 10 m in particle diameter).
Mobile phase: A mixture of 10 mL of acetic acid with
1000 mL of a mixture of water and acetonitrile (55 : 45).
Flow rate : Adjust the flow rate so that the retention
time of Dehydrocholiric Acid is about 12 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, dehydrocholinic acid and internal
standard are eluted in this order with the resolution between their peaks being not less than 5.0.
above operating conditions, the relative standard deviation of the ratios of the peak areas of dehydrocholinic acid to that of the ineternal standard is not more than 2.0%.
H
H
CH3
CH3
O
OH
H
H
CH3
O
H
CH2OH
O
O
OH
H
H
H
O
OH
H
OH H
H
HO
H
OH
C47H74O19: 943.08
Deslanoside, when dried, contains not less than 90.0%
and not more than 102.0% of deslanoside (C47H74O19).
Description Deslanoside is a colorless or white crystal
or white crystalline powder.
Deslanoside is freely soluble in anhydrous pyridine, sparingly soluble in methanol, slightly soluble in ethanol
and practically insoluble in water or in ether.
Deslanoside is hygroscopic.
Identification Transfer 1 mg of Deslanoside to a small
test tube, about 10 mm in inside diameter, dissolve in 1
mL of a solution of ferric chloride in glacial acetic acid
(1 in 10000) and underlay gently with 1 mL of sulfuric
acid: at the zone of contact of two liquids, a brown ring
is produced and the color of the upper layer near to the
contact zone changes gradually to blue through purple
and the entire glacial acetic acid layer changes to a bluegreen color through a deep blue color.
+8.5 (after drying, 0.50 g, anhydrous pyridine, 25 mL,
100 mm).
mg of Deslanoside in 10 mL of ethanol and 3 mL of water by warming, cool and dilute to 100 mL with water:
(2) Related substancesDissolve 10.0 mg of Deslanoside in exactly 5 mL of methanol and use this solution
as the test solution. Dissolve 1.0 mg of Deslanoside RS
in exactly 5 mL of methanol and use this solution as the

of dichloromethane, methanol and water (84 : 15 : 1) to a
distance of about 13 cm and air-dry the plate. Spray
evenly dilute sulfuric acid on the plate and heat the plate
o
at 110 C for 10 minutes: the spots other than the principal spot from the test solution are not larger than and
P2O5, 60 C, 4 hours).
Assay Dissolve about 12 mg each of Deslanoside and
Deslanoside RS, previously dried and accurately
weighed, in 20 mL each of methanol, add water to make
exactly 100 mL and use these solutions as the test solution and the standard solution, respectively. Pipet 5.0 mL
each of the test solution and the standard solution, transfer to light-resistant, volumetric flasks, shake well with 5
mL each of picric acid TS and 0.5 mL each of a solution
of sodium hydroxide (1 in 10), diluted methanol (1 in 4)
to make exactly 25 mL and allow to stand at a temperature between 18 C and 22 C for 25 minutes. Determine
solution prepared with 5 mL of diluted methanol (1 in 5)
in the same manner as the blank.
Amount (mg) of deslanoside (C47H74O19)

A
= amount (mg) of Deslanoside RS T
AS
Deslanoside Injection
Deslanoside Injection is an aqueous solution for injection.
Deslanoside Injection contains not less than 90.0% and
not more than 110.0% of the labeled amount of deslanoside (C47H74O19: 943.08).
Method of Preparation Dissolve Deslanoside in 10
vol% of ethanol and prepare as directed under Injections.
Deslanoside Injection may contain Glycerin. Deslanoside
Injection may be prepared with a suitable amount of
Ethanol and Water for Injection.
Description Deslanoside Injection is a clear and colorless liquid.
Identification (1) Place a volume of Deslanoside Injection, equivalent to 2 mg of Deslanoside according to

the labeled amount, in a separatory funnel, add sodium
chloride in the ratio of 0.2 g to each mL of this solution
and extract with three 10 mL volumes of chloroform.
Combine the chloroform extracts, mix uniformly, pipet
15 mL of this solution and evaporate the chloroform under reduced pressure. Proceed with the residue as directed in the Identification under Deslanoside.
(2) Place a volume of Deslanoside Injection, equivalent to 1 mg of Deslanoside according to the labeled
amount, in a separator, add sodium chloride in the ratio
of 0.2 g to each mL of this solution, and extract with
three 5-mL portions of chloroform. Combine the chloroform extracts, evaporate the chloroform under reduced
pressure, dissolve the residue in 5 mL of methanol, and
1 mg of Deslanoside RS in 5 mL of methanol, and use
with these solutions as directed under Thin-layer Chromatography. Spot 20 L each of these solutions on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, methanol
and water (84 : 15 : 1) to a distance of about 13 cm and
air-dry the plate. Spray evenly dilute sulfuric acid upon
the plate, and heat the plate at 110 C for 10 minutes: the
spots from the test solution and the standard solution
show a black color and have the same Rf value.
It

Assay Measure exactly a volume of Deslanoside Injection, equivalent to about 3 mg of deslanoside (C47H74O19).
Add 5 mL of methanol and water to make exactly 25 mL.
Use this solution as the test solution and proceed as directed in the Assay under Deslanoside.
Amount (mg) of deslanoside (C47H74O19)

1
A
= amount (mg) of Deslanoside RS T 4
AS
KP 9 273
constant mass).
Desoximetasone
O
H
CH3
OH
HO
H
H
CH3
CH3
F
O
C22H29FO4 : 376.46
Desoximetasone contains not less than 97.0% and not

more than 103.0% of desoximetasone (C22H29FO4), calculated on the dried basis.
Description Desoximetasone is a white, crystalline
powder.
Desoximetasone is very soluble in ethanol, in acetone or
in chloroform and practically insoluble in water.
Desoximetasone and Desoximetasone RS as directed in
(2) Dissolve 0.1 g of Desoximetasone in a mixture of
chloroform and ethanol (3:1) to make 10 mL and use this
solution as the test solution. Separately, dissolve 0.1 g of
Desoximetasone RS in a mixture of chloroform and
ethanol (3:1) to make 10 mL and use this solution as the
and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and ethyl acetate (1:1) to a distance of about 10 cm, and air-dry the
plate. Expose the plate with ultraviolet light (main wavelength 254 nm) and spray evenly the plate with ptoluenesulfonic acid in ethanol (1 in 5): the Rf value of
the principal spot obtained from the test solution corresponds to that from the standard solution.
Melting Point Between 206 C and 218 C, but the
range between beginning and end of melting does not
exceed 4 C.
-112 (0.1 g, after drying, chloroform, 20 mL, 100 mm).
Purity Heavy metalsProceed with 1.0 g of Desoximetasone according to Method 2, and perform the test.
Assay Weigh accurately about 40 mg of Desoximetasone, add methanol to make exactly 100 mL, pipet 10.0
mL of this solution, add a mixture of methanol and acetonitrile (1:1) to make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately
about 20 mg of Desoximetasone RS, add methanol to
make exactly 50 mL, pipet 10.0 mL of this solution, add
a mixture of methanol and acetonitrile (1:1) to make exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution
Chromatography according to the following operating
conditions and determine the height of the desoximetasone peak in the test solution, HT , and in the standard
solution, H S .
Amount (mg) of desoximetasone (C22H29FO4)
= amount (mg) of Desoximetasone RS H T
HS
octylsilanized silica gel for liquid chromatography (3-10
Mobile phase: A mixture of methanol, water and glacial acetic acid (65:35:1).
System suitability
with 10 L of the standard solution under the above operating conditions, the symmetry factor for desoximetasone peak is not more than 2.0.
above operating conditions, the relative standard deviation of the heights of desoximetasone peak is not more
than 2.0%.
Dexamethasone
O
H
CH2OH
H3C
HO
OH
H3C
CH3
H
C22H29FO5: 392.46
Dexamethasone, when dried, contains not less than
97.0% and not more than 102.0% of dexamethasone
(C22H29FO5).
Description Dexamethasone is a white to pale yellow
crystal or crystalline powder and is odorless.
Dexamethasone is sparingly soluble in methanol, in
ethanol or in acetone and practically insoluble in water.
Identification (1) Proceed with 10 mg of Dexamethasone as directed under the Oxygen Flask Combustion
hydroxide TS and 20 mL of water as the absorbing liquid: the solution responds to the Qualitative Tests for
fluoride.
(2) Dissolve separately 1.0 mg of Dexamethasone
and Dexamethansone RS in 10 mL of ethanol, pipet 2.0
mL each of these solutions, add 10 mL each of phenylhydrazine hydrochloride TS, shake and warm on a water-
bath at 60 for 20 minutes. Cool and determine the absorption spectra with these solutions as directed under
the Ultraviolet-visible Spectrophotometry using a solution, prepared with 2.0 mL of ethanol in the same manner,
as the blank: both spectra exhibit similar intensities of
(3) Determine the infrared spectra of Dexamethasone
and Dexamethasone RS, previously dried, according to
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve Dexamethasone and Dexamethasone RS in acetone, respectively, evaporate to dryness
and repeat the test on the residues.
D : Between +86 and
Purity (1) Heavy metalsProceed with 1.0 g of Dexamethasone according to Method 2 and perform the test.
(2) Related SubstancesDissolve 0.10 g of Dexamethasone in 10 mL of acetone and use this solution as
the test solution. Pipet 2 mL of the test solution, add a solution, prepared by dissolving 1.32 g of ammonium formate in water to make 1000 mL and adjusted to pH 3.6
with formic acid, to make 100 mL, and use this solution
as the test solution. To exactly 1 mL of the test solution,
add the mobile phase to make exactly 100 mL, and use
with exactly 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine
peak area other than dexamethasone is not larger than the
peak area of dexamethasone obtained from the standard
solution, and the total area of the peaks other than the
peak of dexamethasone from the sample solution is not
larger than 2 times the peak area of dexamethasone from
the standard solution
diameter and 25 cm in length, packed with phenylsilanized silica gel for liquid chromatography (5 m in particle diameter ).
about 25 C.
Mobile phase: Dissolve 1.32 g of ammonium formate
in 1000 mL of water, and adjust the pH to 3.6 with formic acid. To 670 mL of this solution, add 330 mL of acetonitrile.
time of dexamethasone is about 13 minutes.
System suitability
the standard solution add the mobile phase to make exactly 10 mL. Confirm that the peak area of dexamethasone obtained with 10 L of this solution is equivalent to
8 to 12% of that with 10 L of the standard solution.
with 10L of the standard solution under the above operating conditions, the number of theoretical plates and the
symmetry factor of the peak of dexamethasone are not
times with 10 mL of the standard solution under the
above operating conditions, the relative standard deviation of the peak area of dexamethasone is not more than
1.0%.
as the retention time of dexamethasone beginning after
the solvent peak.
hours).
KP 9 275
Assay Dissolve about 10 mg each of Dexamethasone
and Dexamethasone RS, previously dried and accurately
weighed, in 70 mL each of diluted methanol (1 in 2), add
exactly 5 mL each of the internal standard solution, then
add diluted methanol (1 in 2) to make exactly 100 mL
and QS , of the peak area of dexamethasone of the test

solution and the standard solution to that of the internal
standard, respectively.
Amount (mg) of dexamethasone (C22H29FO5)
= amount (mg) of Dexamethasone RS QT
QS
Internal standard solutionA solution of propyl parahydroxybenzoate in diluted methanol (1 in 2) (1 in

1000).
about 25 C.
1).
time of dexamethasone is about 6 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, dexamethasone and the internal standard are eluted in this order with the resolution between
above operating conditions, the relative standard deviation of the ratio of the peak area of dexamethasone to
tight containers.
Method of Preparation Prepare as directed under Tablets, with Dexamethasone.

Identification Evaporate 10 mL of the methanol extract of Dexamethsone Tablets, obtained as directed under preparation of the test solution in the Assay on a water-bath to dryness, dissolve the residue in 1 mL of chloroform and use this solution as the test solution. Separately, weigh a quantity of Dexamethasone RS and dissolve in chloroform to contain 500 g per mL and use
of the test solution and 20 L of the standard solution on
a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methylene chloride and
methanol (45 : 4) to a distance of about 15 cm and airdry the plate. Examine under ultraviolet light (main wavelength: 254nm): the Rf values of the principal spot obtained from the test solution and the standard solution are
the same.
Dissolution Test Perform the test with 1 tablet of Dexamethasone Tablets at 100 revolutions per minute according to Method 1 under the Dissolution Test, using
500 mL of diluted hydrochloric acid (1 in 100). After 45
minutes of the start of the test, extract a filtered aliquot
of dissolution solution, equivalent to about 200 g of
Dexamethasone, with three 15 mL volumes of chloroform. Evaporate the combined chloroform extract in a
water-bath to dryness, cool, dissolve the residue in 20
mL of ethanol and use this solution as the test solution.
Separately weigh a quantity of Dexamethasone RS, previously dried at 105 C for 3 hours, dissolve in methanol
to contain 10 g per mL and use this solution as the
standard solution. Transfer 20 mL each of the test solution and the standard solution to an Erlenmeyer flask,
add 2.0 mL of a solution, dissolve 50 mg of blue tetrazolium in 10 mL of methanol. Use 20 mL ethanol for blank
test. Add 2 mL of a mixture of tetra-methylammonium
hydroxide and ethanol (1 : 9) to each of these flasks and
mix. Immediately determine the absorbance, AT and
AS , of the test solution and the standard solution, respectively, at the wavelength of maximum absorption
around 525 nm as directed under the Ultraviolet-visible
Spectrophotometry in contrast with blank solution.
Not less than 70% of the labeled amount of C22H29FO5 is
dissolved in 45 minutes.
Dexamethasone Tablets
Dexamethasone Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of dexamethasone (C22H29FO5: 392.47).
A
= 10 C 1 T
V
AS
C: Concentration of standard solution (g/mL),

V: Volume of the aliquot extracted with chloroform
(mL).

to the following procedure. Place 1 tablet of Dexamethasone Tablets in a separatory funnel with 15 mL of water
and swirl to dissolve the tablet completely. Extract with
four 10 mL volumes of chloroform, filter each volume
through chloroform-washed cotton into a volumetric
flask, add chloroform to make 50 mL and mix. Pipet a
volume of this solution, equivalent to about 200 g of
Dexamethasone into a glass-stoppered Erlenmeyer flask,
evaporate the chloroform on a water-bath to dryness,
cool and dissolve the residue in 20.0 mL of alcohol. Separately pipet 20 mL of standard solution in Dissolution
test into a stoppered Erlenmeyer flask. Calculate the
amount of Dexamethasone in the same manner of Dissolution Test.
System suitability
System performance : Dissolve 2 mg of methyl poxybenzoate and 4 mg of propyl p-oxybenzoate in 100
mL of a mixture of water and methanol (1:1). When the
test is performed with 10 mL of the solution as directed
under the above operating conditions, methyl poxybenzoate and propyl p-oxybenzoate are eluted in this
less than 5.0.
above operating conditions, the relative standard deviation of the ratio of the peak area of dexamethason to the
peak area of the internal standard is not more than 3.0%.

A
= C T
V
Dexamethasone Disodium
Phosphate
AS
C: Concentration of standard solution (g/mL),

V: Volume of the solution, equivalent to 200 g of
Dexamethasone (mL).
Assay Weigh and finely powder not less than 20 Dexamethasone Tablets. Weigh accurately a portion of the
powder, equivalent to about 10 mg of Dexamethasone,
transfer to a 100 mL volumetric flask and add 30 mL of
diluted methanol (1 in 2). After shaking for 30 minutes,
add 5 mL exactly of the internal standard solution, diluted methanol (1 in 2) to make 100 mL and mix. Filter
and use the filtrate as the test solution. Separately, weigh
accurately about 10 mg of Dexamethasone RS, transfer
to a 100 mL volumetric flask and add 30 mL of diluted
methanol (1 in 2). Add 5 mL of the internal standard solution, diluted methanol (1 in 2) to make 100 mL, mix
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and determine
the peak area ratios, QT and QS ,, of Dexamethasone
for the test solution and the standard solution to the internal standard, respectively.

= Amount (mg) of Dexamethasone RS
QT
QS
Internal standard solutionA solution of propyl poxybenzoate in a mixture of water and methanol (1:1) (1
in 1000)
Use the operating conditions as directed under the
Assay of Dexamethasone.
ONa
O
H
H3C
HO
OH
H
H3C
ONa
CH3
H
C22H28FNa2O8P: 516.41
Dexamethasone Disodium Phosphate contains not less
than 97.0% and not more than 102.0% of dexamethasone
disodium phosphate (C22H28FNa2O8P), calculated on the
anhydrous and ethanol-free basis.
Description Dexamethasone Disodium Phosphate is a
white to pale yellowish crystalline powder, is odorless or
has slightly ethanol-like smell.
Dexamethasone Disodium Phosphate is freely soluble in
water, slightly soluble in ethanol, very slightly soluble in
dioxane and practically insoluble in ether.
Dexamethasone Disodium Phosphate is hygroscopic.
Identification (1) Transfer 20 mg of Dexamethasone
Disodium Phosphate to a centrifugal tube, add 5 mL of
alkaline phosphatase TS, vigorously shake and allow to
stand for 30 minutes. Add 5 mL of ethyl acetate, vigorously shake, centrifuge and use the ethyl acetate layer
(upper layer) as the test solution. Separately, transfer 15
mg of Dexamethasone RS to a volumetric flask, add
ethyl acetate to dissolve, add ethylacetate to make 5 mL
KP 9 277
a plate of silica gel for thin-layer chromatography. Develop the plate in a mixture of chloroform, methanol and
water (180 : 15 : 1) to a distance of about 15 cm and airdry the plate. Observe under ultra-violet light (main wavelength: 254 nm). The Rf value of the principal spot
obtained from the test solution corresponds to the that
obtained from the standard solution.
(2) The residue from the ignition of Dexamethasone
Disodium Phosphate responds to the Qualitative Tests for
sodium and for phosphate.
pH Between 7.5 and 10.5 in a solution (1 in 100).
D : Between +74 and
+82 (calculated on the anhydrous and ethanol-free basic,
0.1 g, water, 10 mL, 100 mm).
Purity (1) Ethanol Transfer about 0.5 g of Dexamethasone Disodium Phosphate, accurately weighed, to a
volumetric flask, add exactly 5 mL of the internal standard solution to dissolve, then add the water to make exactly 10 mL. After shaking, use this solution as the test
solution. Separately, pipet diluted ethanol (1 in 50), determine the specific gravity at 25 C, calculate the
amount of ethanol and use this solution as the standard
stock solution. Pipet 4.0 mL of this solution to a volumetric flask, add exactly 5 mL of the internal standard solution and add water to make exactly 10 mL, shake and use
with 2 L each of the test solution and the standard solution as directed under the Gas Chromatography according to the following conditions and determine the peak
area ratios, QT and QS , of ethanol for the test solution
and the standard solution, respectively, to that of the internal standard.
Amount (%) of C2H5OH = 4 S QT

W
QS

with 5 L of the standard solution under the above operating conditions, the resolution between the peaks of
ethanol and internal standard is not less than 2.0 and factor symmetry for ethanol is not more than 1.5.
the ratios of peak height of ethanol to that of the internal
standard is not more than 4.0%.
The amount of ethanol in Dexamethasone Disodium
Phosphate is not more than 8.0%.
(2) Phosphate ion Dissolve about 50 mg of Dexamethasone Disodium Phosphate, accurately weighed, in
a mixture of 10 mL of water and 5 mL of 1 mol/L sulfuric acid TS in a volumetric flask, by warming, if necessary.
Add 1 mL of each of phosphate reagent A and phosphate
reagent B, dilute with water to make exactly 25 mL, mix,
allow to stand at room temperature for 30 minutes and
use this solution as the test solution. Separately, using 5.0
mL of phosphate standard solution instead of 50 mg of
Dexamethasone Disodium Phosphate, proceed in the
same manner as the preparation of the test solution and
use this solution as the standard solution. Determine absorbances of the test solution and the standard solution at
730 nm as directed under the Ultraviolet-visible Spectrophotometry, using water as the blank. The absorbance of
the test solution is not more than that of the standard solution (not more than 1.0% of phosphate).
Phosphate standard solutionDissolve 143.3 mg of

dried monobasic potassium phosphate, KH2PO4, in water
to make 1000 mL (0.10 mg PO4/mL).
Phosphate reagent ADissolve 5 g of ammonium
molybdate in 0.5 mol/L sulfuric acid TS to make 100
mL.
Phosphate reagent BDissolve 350 mg of pmethylaminophenol sulfate in 50 mL of water, add 20 g
of sodium bisulfite, mix to dissolve and dilute with water
to make 100 mL.
S: Amount of ethanol in the original standard solution

(%),
W: Amount of Dexamethasone Disodium Phosphate
in the test solution (%).
(3) Free Dexamethasone Separately inject 20 L

of the standard solution and the test solution under the
Assay, respectively. Determine the peak areas, AT and
Internal standard solutionA mixture of isopropanol and water (1 in 100).
dard solution, respectively. (not more than 1.0%).
Detector: A hydrogen flame ionization detector.
Column: A glass column, about 4 mm in inside diameter and about 1.8 m in length, packed with copolymer of 4-vinyl pyridine and styrenedivinyl benzene (80 100 mesh in particle diameter).
about 120 C.
System suitability
AS of Dexamethasone of the test solution and the stanAmount (g) of dexamethasone (C22H29FO5)
A
= 1000 C T
AS
C: Concentration of the Dexamethasone RS in the

standard solution (g/mL).
Water Not more than 16.0% (sum of the % of water
content and ethanol content, 0.4 g, direct titration).

Assay Take accurately about 50 mg of Dexamethasone
Disodium Phosphate, dissolve in mobile phase to make
exactly 100 mL. Pipet 5.0 mL of this solution and add
the mobile phase to make exactly 50 mL and use this solution as the test solution. Separately, dissolve a portion
of Dexamethasone Phospahte RS, previously dried at 40
C and 0.67 kPa, in mobile phase to make the concentration of 0.5 mg of Dexamethasone Phospahte per mL and
use this solution as the standard solution (1). Weigh accurately a portion of Dexamethasone RS, previously
dried at 105 C for 3 hours, dissolve in a mixture of methanol and water (1 : 1) to make the concentration of 50
g of Dexamethasone RS per mL and use this solution as
the standard solution (2). Pipet 10.0 mL of the standard
solution (1) and 1.0 mL of the standard solution (2), add
20 L each of the test solution and standard solution as
the following conditions. Determine the peak area, AT
and AS of Dexamethasone Phosphate of the test solution and the standard solution, respectively.
Amount (mg) of dexamethasone disodium phosphate
516.41
A
(C22H28FNa2O8P) = 472.45 C T
A
S
C: Concentration of the Dexamethasone Phospahte RS

in the standard solution (g/mL).
phenylatedsilica gel for liquid chromatography.
Mobile phase: To 7.5 mL of the triethylamine, add
water to make 1000 mL. Adjust by the the addition of
phosphoric acid to a pH of 5.4. To 740 mL of this solution, add 260 mL of methanol.
System suitability
System performance : When the procedure is run
with 10 L of the standard solution under the above operating conditions, and calculate the resolution, dexamethasone and dexamethasone phosphate are eluted in this
order and the resolution between the dexamethasone
peak and dexamethasone phosphate peak is not less than
1.8.
above operating conditions, the relative standard deviation of the peak area is not more than 1.0%.
Dexamethasone Disodium
Phosphate Injection
Dexamethasone Disodium Phosphate Injection is an
aqueous solution for Injection.
Dexamethasone Disodium Phosphate Injection contains
not less than 90.0% and not more than 115.0% of the labeled amount of dexamethasone phosphate (C22H30FO8P:
472.45).
Method of Preparation Prepare as directed under Injections with the Dexamethasone Disodium Phosphate.
Identification Pipet a volume of Dexamethasone Disodium Phosphate Injection, equivalent to about 10 mg of
dexamethasone phosphate, into a volumetric flask, add
water to make 100 mL and mix. Pipet 5 mL of this solution into a separatory funnel and wash with two 10 mL
volumes of water-washed methylene chloride, discarding
the washings. Transfer the solution into a glass-stoppered
tube and add 5 mL of alkaline phosphatase solution, prepared by dissolving 50 mg of alkaline phosphatase in 50
mL of pH 9 buffer with magnesium. Allow to stand at 37
C for 45 minutes and extract with 25 mL of methylene
chloride. Evaporate 15 mL of the methylene chloride extract in a steam-bath to dryness and dissolve the residue
in 1 mL of methylene chloride and use this solution as
the test solution. Separately, dissolve a portion of Dexamethasone RS in methylene chloride to contain 300 g
solutions as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the standard
solution on a plate of silica gel for thin-layer chromatography, respectively. Develop the plate with a mixture of
chloroform, acetone, water (50 : 50 : 1) to a distance of
about 15 cm and air-dry the plate. Spray evenly diluted
sulfuric acid (1in 2) upon the plate and heat the plate at
105 C until black or brown spots appear. The spot from
the test solution shows the same Rf value as the spot
Sterility Test

dexamethasone phosphate.
Foreign Insoluble Matter Test
ment.
It meets the require-

It
KP 9 279

phate (C22H30FO8P: 472.45).

Ophthalmic Ointments, with the Dexamethasone Disodium Phosphate.

Dexmethasone Disodium Phosphate Injection, equivalent
to about 8 mg of dexamethasone phosphate
(C22H30FO8P), to a volumetric flask. Dilute with mobile
phase to make 100 mL and mix and use this solution as
dexamethasone phosphate RS, previously dried at 40 C
under 0.67 kPa, dissolve in mobile phase to make the
concentration of 80 g of dexamethasone phosphate per
mL and use this solution as the standard solution. Prepare
this solution at the time of use. Perform the test with 20
l each of the test solution and the standard solution as
the following conditions. Determine the peak area, AT
Identification Dissolve 50 mg of alkaline phosphatase

to 50 mL of pH 9 buffer with magnesium. Transfer 5 mL
of this solution to a stoppered test tube containing 5 mL
of the test solution described in the Assay. Allow to stand
at 37 C for 45 minutes, add 25 mL of dichloromethane
and shake for 2 minutes to mix. Proceed with the dichloromethane extracts as directed in the Identification under
Dexmethasone Disodium Phosphate Injection after evaporating 15 mL of the dichloromethane extract to residue.
and AS , of the dexamethasone phosphate of the test solution and the standard solution, respectively.
Test for Metal Particles It meets the requirement.
Amount (mg) of dexamethasone phosphate

A
(C22H30FO8P) = 0.1 C T
AS
C: Concentration of the dexamethasone phosphate

RS in the standard solution (g/mL),
potassium phosphate buffer and methanol (1 : 1).
System suitability
above operating conditions, the relative standard deviation of the peak area of dexamethasone phosphate is not
more than 1.5%.
Dexamethasone Disodium Phosphate Ophthalmic Ointment

Dexamethasone Disodium Phosphate Ophthalmic Ointment contains not less than 90.0% and not more than
115.0% of the labeled amount of dexamethasone phos-
Assay Weigh accurately a portion of Dexamethasone

Disodium Phosphate Ophthalmic Ointment, equivalent to
3 mg of dexamethasone phosphate (C22H30FO8P) and
transfer to a beaker. Add 65 mL of ethanol-phosphate
buffer and heat the solution just to boiling. Transfer the
contents to a separatory funnel containing 45 mL of
isooctane, shake for 1 minute to mix and transfer the
lower layer to a volumetric flask. Wash the beaker with
two volumes of 15 mL of ethanol phosphate buffer, extract the rinsate with isooctane and mix the lower layer to
the volumetric flask. Fill the volumetric flask with ethanol-phosphate buffer to make 100 mL, filter and use this
a portion of dexamethasone phosphate RS, previously
dried at 40 C under 0.67 kPa, dissolve in ethanolphosphate buffer to make 30 g of dexamethasone phosphate per mL and use this solution as the standard solution. Perform the test with 20 l each of the test solution
and standard solution as directed under the Liquid
Determine the dexamethasone phosphate peak area, AT
and AS , of the test solution and standard solution, respectively.

Amount (mg) of dexamethasone phosphate
A
(C22H30FO8P) = 0.1 C T
AS
C: Concentration of the dexamethasone phosphate

RS in the standard solution (g/mL).

Mobile phase: A mixture of methanol and 0.05 mol/L
phosphate buffer(52 : 48).
System suitability
System Repeatability: When the test is repeated 5
above operating conditions, the relative standard deviation of the peak area of dexamethasone phosphate is not
more than 1.5%.
tight containers.
Dextran 40
Dextran 40 is a product obtained by partial decomposition of polysaccharide, which is produced by fermentation of sucrose with Leuconostoc mesenteroides van
Tieghem (Lactobacillaceae) and the average molecular
weight is about 40000.
Dextran 40, when dried, contains not less than 98.0%
and not more than 102.0% of dextran.
Description Dextran 40 is a white, amorphous powder,
Dextran 40 is practically insoluble in ethanol or in ether.
Dextran 40 dissolves gradually in water.
Dextran 40 is hygroscopic.
Identification Take 1 mL of a solution of Dextran 40
(1 in 3000) and add 2 mL of anthrone TS: a blue-green
color is observed and turns gradually dark blue-green.
Then to this solution, add 1 mL of diluted sulfuric acid (1
in 2) or 1 mL of glacial acetic acid: the solution does not
change in color.
pH Dissolve 1.0 g of Dextran 40 in 10 mL of water:
g of Dextran 40 in 10 mL of water by warming: the solution is clear and colorless.
(2) ChloridePerform the test with 2.0 g of Dextran
40. Prepare the control solution with 1.0 mL of 0.01
(3) Heavy metalsProceed with 1.0 g of Dextran 40
according to Method 1 and perform the test (not more
than 20 ppm).
Dextran 40 according to Method 1 and perform the test
(not more than 1.3 ppm).
(5) NitrogenWeigh accurately about 2 g of Dextran 40, previously dried, and perform the test as directed
under the Nitrogen Determination, where 10 mL of sulfuric acid is used for decomposition and 45 mL of a solu-
tion of sodium hydroxide (2 in 5) is added: the amount of

nitrogen (N: 14.007) is not more than 0.010%.
(6) Reducing substancesWeigh exactly 3.00 g of
Dextran 40, previously dried, dissolve in water to make
Separately, weigh exactly 0.450 g of glucose, previously
dried, dissolve in water to make exactly 500 mL and use
this solution as the standard solution. Pipet 5.0 mL each
of the test solution and the standard solutions and add
water to make exactly 50 mL. Pipet 5.0 mL each of these
solutions, add 5.0 mL of alkaline copper TS and heat for
15 minutes in a water-bath. After cooling, add 1 mL of a
solution of potassium iodine (1 in 40) and 1.5 mL of dilute sulfuric acid and titrate with 0.005 mol/L sodium
thiosulfate VS (indicator: 2 mL of starch TS). The titrant
consumed for the test solution is not less than that for the
standard solution.
hours).
Viscosity (1) Dextran 40Weigh accurately about 0.2
to 0.5 g of Dextran 40, previously dried, dissolve in water to make exactly 100 mL and use this solution as the
test solution. Perform the test with the test solution and
with water as directed in Method 1 under the Viscosity
Determination at 25 C: the intrinsic viscosity is between
0.16 and 0.19.
(2) High-molecular fractionWeigh accurately
about 6 g of Dextran 40, previously dried, dissolve in
water to make exactly 100 mL and transfer to a flask.
Add slowly enough methanol to obtain 7% to 10% of the
precipitate (usually 80 to 90 mL) at 25 1 C with stirring. Dissolve the precipitate at 35 C in a water-bath
with occasional shaking and allow to stand for more than
15 hours at 25 1 C. Remove the supernatant by decantation and heat the precipitate of the lower layer to dryness on a water-bath. Dry the residue and determine the
intrinsic viscosity of the dried substance as directed in
(1): the value is not more than 0.27.
(3) Low-molecular fractionWeigh accurately
Add slowly enough methanol to obtain 90% to 93% of
the precipitate (usually 115 to 135 mL) at 25 1 C with
stirring, centrifuge at 25 C and evaporate the supernatant to dryness on a water-bath. Dry the residue and determine the intrinsic viscosity of the dried substance as
directed in (1): the value is not less than 0.09.
Antigenicity Dissolve 10.0 g of Dextran 40 in Isotonic
Sodium Chloride Injection to make 100 mL, sterilize and
use this solution as the test solution. Inject 1.0 mL of the
test solution on three occasions at intervals of 2 days into
the peritoneal cavity of each of 4 well-nourished, healthy
guinea pigs weighing 250 g to 300 g. Inject 0.10 mL of
KP 9 281
horse serum into the peritoneal cavity of each of 4 guinea
pigs of another group as a control. Inject 0.20 mL of the
test solution intravenously to each of 2 guinea pigs of the
first group 14 days after the first intraperitoneal injection
and each of the remaining 2 guinea pigs 21 days after the
injection and inject 0.20 mL of horse serum intravenously in the same manner each guinea pig of the second
group. Observe the signs of respiratory distress, collapse
or death of the animals for 30 minutes after each intravenous injection and 24 hours later: the animals of the
first group exhibit no signs mentioned above. All the animals of the second group exhibit symptoms of respiratory distress or collapse and not less than 3 animals are
killed.
Pyrogen Test Dissolve 10.0 g of Dextran 40 in Isotonic Sodium Chloride Injection to make 100 mL and perform the test: this solution meets the requirement of the
Pyrogen Test.
Assay Weigh accurately about 3 g of Dextran 40, previously dried, dissolve in water to make exactly 50 mL
and use this solution as the test solution. Determine the
optical rotation with the test solution as directed under
the Optical Rotation Determination in a 100 mm cell at
20 1 C.
Amount (mg) of Dextran 40 = D 253.8

Dextran 40 Injection
Dextran 40 Injection is an aqueous solution for injection.
Dextran 40 Injection contains not less than 9.5 w/v% and
not more than 10.5 w/v% of Dextran 40.
Dextran 40
10 g
Isotonic Sodium Chloride Injection
To make 100 mL
Description Dextran 40 Injection is a clear and colorless liquid, and is slightly viscous.
Identification (1) Dilute 1 mL of Dextran 40 Injection
with water to make 200 mL, pipet 1 mL of this solution
and add 2 mL of anthrone TS: a blue-green color is observed and turns gradually dark blue-green. Then to this
solution, add 1 mL of diluted sulfuric acid (1 in 2) or 1
mL of glacial acetic acid: the solution does not change in
color.
(2) Dextran 40 Injection responds to the Qualitative
Tests for sodium salt and for chloride.
pH
Viscosity Measure exactly 2 mL to 5 mL of Dextran 40

Injection, add Isotonic Sodium Chloride Injection to
make exactly 100 mL and use this solution as the test solution. Perform the test with the test solution and with
Isotonic Sodium Chloride Injection as directed in Meo
thod 1 under the Viscosity Determination at 25 C : the

intrinsic viscosity is between 0.16 and 0.19. Calculate the
concentration of the test solution (g/100 mL) as directed
in the Assay.
Bacterial Endotoxins
Dextran 40 Injection.
Less than 0.5 EU per mL of

It

Assay Take exactly 30 mL of Dextran 40 Injection, add
test solution. Determine the optical rotation, D, with the
test solution as directed under the Optical Rotation Determination in a 100-mm cell at 20 1 C.
Amount (mg) of Dextran 40 in 100 mL of Dextran 40 Injection = D 846.0

Packaging and Storage Preserve in hermetic containers and plastic containers for aqueous injections may be
used.
Dextran 70
Dextran 70 is a product obtained by partial decomposition of polysaccharide, which is produced by fermentation of sucrose with Leuconostoc mesenteroides van
Tieghem (Lactobacillaceae) and the average molecular
weight is about 70000.
Dextran 70, when dried, contains not less than 98.0%
and not more than 102.0% of Dextran 70.
Description Dextran 70 is a white, amorphous powder
and is odorless and tasteless.
Dextran 70 is practically insoluble in ethanol or in ether.
Dextran 70 dissolves gradually in water.

Dextran 70 is hygroscopic.
Identification Perform the test according to Identification of Dextran 40.
pH Dissolve 3.0 g of Dextran 70 in 50 mL of water:
g of Dextran 70 in 10 mL of water with warming: the solution is clear and colorless.
(2) ChloridePerform the test with 2.0 g of Dextran
70. Prepare the control solution with 1.0 mL of 0.01
mol/L hydrochloric acid (not more than 0.018%).
(3) Heavy metalsProceed with 1.0 g of Dextran 70
Dextran 70 according to Method 1 and perform the test
(not more than 1.3 ppm).
(5) NitrogenWeigh accurately about 2 g of Dextran 70, previously dried, perform the test as directed under the Nitrogen Determination, where 10 mL of sulfuric
acid is used for decomposition and 45 mL of a solution
of sodium hydroxide (2 in 5) is added: the amount of Nitrogen (N: 14.007) is not more than 0.010%.
(6) Reducing substancesWeigh exactly 3.00 g of
Dextran 70, previously dried, dissolve in water to make
Separately, weigh exactly 0.300 g of glucose, previously
dried, dissolve in water to make exactly 500 mL and use
this solution as the standard solution. Pipet 5.0 mL each
of the test solution and the standard solution and add water to make exactly 50 mL, respectively. Pipet 5.0 mL
each of these solutions, add 5.0 mL of alkaline copper TS
and heat for 15 minutes in a water-bath. After cooling,
add 1 mL of a solution of potassium iodine (1 in 40) and
1.5 mL of dilute sulfuric acid and titrate with 0.005
mol/L sodium thiosulfate VS (indicator: 2 mL of starch
TS). The titrant consumed for the test solution is not less
than that for the standard solution.
hours).
Viscosity (1) Dextran 70Weigh accurately about 0.2
to 0.5 g of Dextran 70, previously dried, dissolve in water to make exactly 100 mL and use this solution as the
test solution. Perform the test with the test solution and
with water as directed in Method 1 under the Viscosity
Determination at 25 C: the intrinsic viscosity is between
0.21 and 0.26.
(2) High-molecular fractionWeigh accurately
Add slowly enough methanol to obtain 7% to 10% of the

precipitate (usually 75 to 85 mL) at 25 1 C with stirring. Dissolve the precipitate at 35 C in a water-bath
with occasional shaking and allow to stand for more than
15 hours at 25 1 C. Remove the supernatant by decantation and heat the precipitate of the lower layer on a water-bath to dryness. Dry the residue and determine the intrinsic viscosity of the dried residues as directed in (1):
the value is not more than 0.35.
(3) Low-molecular fractionWeigh accurately
Add slowly enough methanol to obtain 90% to 93% of
the precipitate (usually 110 to 130 mL) at 25 1 C with
stirring, centrifuge at 25 C and evaporate the supernatant to dryness on a water-bath. Dry the residue and determine the intrinsic viscosity of the dried substance as
directed in (1): the value is not less than 0.10.
Antigenicity Dissolve 6.0 g of Dextran 70 in Isotonic
Sodium Chloride Injection to make 100 mL, sterilize and
use this solution as the test solution. Perform the test according to Antigenicity under Dextran 40
Pyrogen Test Dissolve 6.0 g of Dextran 70 in Isotonic
Sodium Chloride Injection to make 100 mL and perform
the test: this solution meets the requirement of the Pyrogen test.
Assay Weigh accurately about 3 g of Dextran 70, previously dried, dissolve in water to make exactly 50 mL
and use this solution as the test solution. Determine the
optical rotation, D, as directed under the Optical Rotation Determination in a 100-mm cell at 20 1 C.
Amount (mg) of Dextran 70 = D 253.8

Dextran 70 Injection
Dextran 70 Injection is an aqueous solution for injection.
Dextran 70 Injection contains not less than 5.7 w/v% and
not more than 6.3 w/v% of Dextran 70.
Dextran 70
6g
Isotonic Sodium Chloride Injection
To make 100 mL
Description Dextran 70 Injection is a clear and colorless liquid and is slightly viscous.
KP 9 283
Identification (1) Dilute 1 mL of Dextran 70 Injection

with water to make 200 mL and to 1 mL of this solution,
add 2 mL of anthrone TS: a blue-green color develops
and turns gradually dark blue-green. Add 1 mL of diluted
sulfuric acid (1 in 2) or 1 mL of glacial acetic acid: the
solution does not change in color.
(2) Dextran 70 Injection responds to the Qualitative
Tests for sodium salt and for chloride.
pH

Bacterial Endotoxins
Dextran 70 Injection.

It

It meets the requirement
Viscosity Take 4 to 8 mL of Dextran 70 Injection, add
Isotonic Sodium Chloride Injection to make exactly 100
mL and use this solution as the test solution. Perform the
test with the test solution and with Isotonic Sodium
Chloride Injection as directed in Method 1 under the Viscosity Determination at 25 C: the intrinsic viscosity is
between 0.21 and 0.26. Calculate the concentration of the
test solution (g/100 mL) as directed in the Assay.
Assay Determine the optical rotation, D, as directed
under the Optical Rotation Determination in a 100-mm
cell at 20 1 C.
Amount (mg) of Dextran 70 in 100 mL of Dextran 70 Injection = D 507.6

used.
Dextromethorphan
Hydrobromide Hydrate
CH3
H
N
HBr
CH3O
H2O
C18H25NOHBrH2O: 370.32
Dextromethorphan Hydrobromide Hydrate contains not
less than 98.0% and not more than 101.0% of dextromethorphan hydrobromide (C18H25-NOHBr), calculated on
Description
Dextromethorphan Hydrobromide Hydrate is a white crystal or crystalline powder.
Dextromethorphan Hydrobromide Hydrate is very soluble in methanol, freely soluble in ethanol or in glacial
acetic acid, sparingly soluble in water and practically insoluble in ether.
Melting pointAbout 126 C (insert the capillary
tube into the bath preheated to 116 C and continue the
heating so that the temperature rises at a rate of about 3
C per minute).
solutions of Dextromethorphan Hydrobromide Hydrate
and Dextromethorphan Hydrobromide Hydrate RS (1 in
(2) Determine the infrared spectra of Dextromethorphan Hydrobromide Hydrate and Dextromethorphan Hydrobromide Hydrate RS as directed in the potassium
(3) Take 50 mL of a solution of Dextromethorphan
Hydrobromide Hydrate (1 in 100), add 2 drops of phenolphthalein TS and sodium hydroxide TS until a red
color is absorbed. Add 50 mL of chloroform, shake and
add 5 mL of dilute nitric acid to 40 mL of the water layer.
This solution responds to the Qualitative Tests for bromide.
D : Between + 26 and +
30 (0.34 g, calculated on the anhydrous basis, water, 20
mL, 100 mm).
pH Dissolve 1.0 g of Dextromethorphan Hydrobromide Hydrate in 100 mL of water: the pH of this solution
0.20 g of Dextromethorphan Hydrobromide Hydrate in
20 mL of water: the solution is clear and colorless.
(2) DimethylanilineTake 0.50 g of Dextromethorphan Hydrobromide Hydrate, add 20 mL of water and
dissolve by heating in a water-bath. After cooling, add 2
mL of dilute acetic acid, 1 mL of sodium nitrite TS and
water to make 25 mL: the solution has no more color
than the following control solution.
Control solutionDissolve 0.10 g of dimethylaniline

in 400 mL of water by warming in a water-bath, cool and
add water to make 500 mL. Pipet 5.0 mL of this solution
and add water to make 200 mL. To 1.0 mL of this solution, add 2 mL of dilute acetic acid, 1 mL of sodium nitrite TS and water to make 25 mL.
Diagnostic Sodium Citrate Solution contains not less

than 3.3 w/v% and not more than 4.3 w/v% of sodium citrate hydrate (C6H5Na3O72H2O: 294.10). The requirement as described for aqueous injections under Injections
are applicable.
(3) Heavy metalsProceed with 1.0 g of Dextromethorphan Hydrobromide Hydrate according to Method 4
(4) Phenolic compoundsDissolve 5 mg of Dextromethorphan Hydrobromide Hydrate in 1 drop of dilute
hydrochloric acid and 1 mL of water, add 2 drops of ferric chloride TS and 2 drops of potassium ferricyanide TS,
shake and allow to stand for 15 minutes: no blue-green
color is observed.
(5) Related substancesDissolve 0.25 g of Dextromethorphan Hydrobromide Hydrate in 10 mL of methanol and use this solution as the test solution. Pipet 1.0
mL of the test solution, add methanol to make exactly
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of toluene,
ethyl acetate, methanol, dichloromethane and 13.5 mol/L
ammonia water (55 : 20 : 13 : 10 : 2) to a distance of
about 15 cm and air-dry the plate. Spray evenly bismuth
potassium iodide TS on the plate and then spray evenly
hydrogen peroxide TS on the plate: the spots other than
Sodium Citrate Hydrate
38 g
Water for injection
To make 1000 mL
Water Between 4.0% and 5.5% (0.2 g, volumetric titration, reverse titration).
Assay Weigh accurately about 0.5 g of Dextromethorphan Hydrobromide Hydrate, dissolve in 10 mL of glacial acetic acid and add 40 mL of acetic anhydride. Titrate with 0.1 mol/L perchloric acid VS (potentiometric

= 35.231 mg of C18H25NOHBr
Prepare as directed under Injections, with the above ingredients.

No preservative is added.
Description Diagnostic Sodium Citrate Solution is a
Identification Diagnostic Sodium Citrate Solution responds to the Qualitative Tests for sodium salt and for citrate.
pH
Assay Pipet 5.0 mL of Diagnostic Sodium Citrate Solution and evaporate on a water-bath to dryness. Dry the
residue at 180 C for 2 hours and dissolve in 30 mL of
glacial acetic acid by warming. After cooling, titrate with
0.1 mol/L perchloric acid VS (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.

= 9.803 mg of C6H5Na3O7.2H2O
Diastase
Diastase is an enzyme mainly prepared from malt. Diastase has an amylolytic activity. Diastase contains not less
than 440 starch saccharifying activity units per g. Diastase is usually diluted with suitable diluents.
Description Diastase is a pale yellow to light brown
powder.
Diastase is hygroscopic.
Purity RancidityDiastase has no unpleasant or rancid odor and has no unpleasant or rancid taste.
Diagnostic Sodium Citrate

Solution

hours).
Assay (i) Substrate solutionUse potato starch TS for
KP 9 285
starch digestive activity.
(ii) Test solutionWeigh accurately about 0.1 g of Diastase, and dissolve in water to make exactly 100 mL.
(iii) ProcedureProceed as directed in (i) Measurement
of starch saccharifying activity of (1) Assay for starch
digestive activity under the Digestion Test.
Packaging and Storage Preserve in tight containers at
not more than 30 C.
Diazepam
CH3
O
N
Cl
C16H13ClN2O: 284.74
Diazepam, when dried, contains not less than 98.0% and
not more than 101.0% of diazepam (C16H13ClN2O).
Description Diazepam is a white to pale yellow, crystalline powder, is odorless and has a slightly bitter taste.
Diazepam is freely soluble in acetone, soluble in acetic
anhydride or in ethanol, sparingly soluble in ether,
slightly soluble in dehydrated ethanol and practically insoluble in water.
Identification (1) Dissolve 10 mg of Diazepam in 3
mL of sulfuric acid and observe under ultraviolet light
(main wavelength: 365 nm): the solution shows a yellow-green fluorescence.
(2) Dissolve 2 mg each of Diazepam and Diazepam
RS in 200 mL each of solutions of sulfuric acid in dehydrated ethanol (3 in 1000) and determine the absorption
spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Perform the test with Diazepam as directed under
the Flame Coloration Test (2): a blue to blue-green color
is observed.
Melting Point
(2) ChlorideTake 1.0 g of Diazepam, add 50 mL of

water, allow to stand for 1 hour, with occasional shaking
and filter. To 25 mL of the filtrate, add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control
solution with 0.20 mL of 0.01 mol/L hydrochloric acid
(3) Heavy metalsProceed with 1.0 g of Diazepam
(4) Related substancesDissolve 1.0 g of Diazepam
in 10 mL of acetone and use this solution as the test solution. Pipet 1.0 mL of the test solution and add acetone to
make exactly 100 mL. Pipet 1.0 mL of this solution, add
a fluorescent indicator for thin-layer chromatography.
Develop the plate with a mixture of ethylacetate and
hexane (1 : 1) to a distance of about 12 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
from the test solution are not more intense than that from
hours).
Assay Weigh accurately about 0.6 g of Diazepam, previously dried, dissolve in 60 mL of acetic anhydride and

= 28.474 mg of C16H13ClN2O
tight containers.
Diazepam Injection
%
Absorbance E11cm
[after drying , 2 mg , a solution of sulfuric acid in dehydrated ethanol (3 in 1000), 200 mL].

g of Diazepam in 20 mL of ethanol: the solution is clear
and colorless.
Diazepam Injection contains not less than 90.0% and not

more than 110.0% of the labeled amount of diazepam
(C16H13ClN2O: 284.74).
Method of Preparation Prepare as directed under Injections, with Diazepam.
Description
liquid.
Diazepam Injection is a colorless, clear

thanol (3 in 10000).
Identification (1) Retention time of the principal peak
in the chromatogram of the test solution under the Assay
corresponds to that of the standard solution.
(2) Take Diazepam Injection, equivalent to 10 mg of
Diazepam according to the labeled amount, transfer to a
separatory funnel, add 20 mL of water. After shaking,
add 20 mL of chloroform and shake extensively. Transfer
the chloroform layer to a beaker through a filter with 5 g
of anhydrous sodium sulfate. Wash anhydrous sodium
sulfate with 20 mL of chloroform and add this washing
to the filtrate. Evaporate the filtrate on a water-bath under the flow of air until the volume is reduced to 5 mL,
take out the beaker from the water-bath and evaporate
under the flow of air. Scratch and gather an oily membrane extensively by spatula and dry it in a desiccator
with P2O5 in vacuum at 60 C for 4 hours. Determine the
infrared spectra of the residue and Diazepam RS, previously dried, as directed in the potassium bromide disk
spectra exhibit the similiar intensities of absorption at the
same wavenumbers.
pH Between 6.2 and 6.9
Sterility Test It meets the requirement
Diazepam.
inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 m
35).
System suitability
above operating conditions, the internal standard and the
diazepam are eluted in this order with the resolution between their peaks being not less than 5.0.
under the above operating conditions, the relative standard deviation of the ratios of peak area of diazepam to
Diazepam Tablets
It
Diazepam Tablets contain not less than 90.0% and not

more than 110.0% of the labeled amount of diazepam
(C16H13ClN2O: 284.74).

Method of Preparation Prepare as directed under Tablets, with Diazepam.
Assay Take accurately a volume of Diazepam Injection,

equivalent to about 10 mg of Diazepam, add 10.0 mL of
the internal standard solution and methanol to make exactly 50 mL and use this solution as the test solution.
Separately, weigh accurately about 10 mg of Diazepam
RS add 10.0 mL of the internal standard solution and methanol to make exactly 50 mL and use this solution as the
as the standard solution. Perform the test with 20 L
each of the test solution and the standard solution as directed under the Liquid Chromatography. Calculate the
ratios, QT and QS , of peak areas of Diazepam to that
of the internal standard for the test solution and the standard solution, respectively.
Identification (1) The retention time of the principal

peak in the chromatogram of the test solution under the
Assay corresponds to that of the standard solution.
(2) Weigh a portion of Diazepam Tablets, equivalent
to 10 mg of Diazepam, place in a centrifuge tube, add 2
mL of acetone, shake for 5 minutes, centrifuge and use
the supernatant as the test solution. Separately, weigh a
portion of Diazepam RS, dissolve in acetone to make a
solution containing 5 mg per mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer chromatography. Spot 100 L each of the test solution and the standard solution on a plate of silica gel for
mixture of ethyl acetate and n-heptane (1 : 1) to a distance of about 15 cm and air-dry the plate. Expose it to
an ultraviolet light (main wavelength: 254 nm). The
principal spot from the test solution shows the same
Rf value as that from the standard solution.

Amount (mg) of diazepam (C16H13ClN2O)

= amount (mg) of Diazepam RS
QT
QS
Internal standard solutionp-tolualdehyde in me-
KP 9 287
Dissolution Test Take 1 tablet of Diazepam Tablets

and perform the test using 900 mL of 0.1 mol/L hydrochloric acid as dissolution solution, at 100 revolutions per
minute as directed in the Method 1 under the Dissolution
Test. After 30 minutes from the start of the test, take the
dissolved solution, suitably dilute with dissolution solution, if necessary and use this solution as the test solution.
Separately, dissolve a suitable portion of Diazepam RS to
make a solution with the same concentration as the test
standard solution at a maximum absorption wavelength
of about 242 nm, as directed under the Ultraviolet-visible
Spectrophotometry, using 0.1 mol/L hydrochloric acid
TS as the blank.
The dissolution rate of Diazepam Tablets in 30 minutes

less than 4.0.
above operating conditions, the relative standard deviation of the peak areas of diazepam is not more than 2.0%.
tight containers.
Dibucaine Hydrochloride
N
Amount (mg) of diazepam (C16H13ClN2O)

= amount (mg) of Diazepam RS
AT
AS
inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 m
Mobile phase: A mixture of acetonitrile, water and
methanol(2 : 2 : 1).
System suitability
System performance: Dissolve suitable quantities
of nordazepam RS and Diazepam RS in methanol containing about 0.1 mg each per mL. When the procedure is
run with 10 L of this solution under the above operating
conditions, nordazepam and Diazepam are eluted in this
OCH 2CH2CH2CH3
HCl
NHCH2CH2N(CH2CH3)2

Assay Weigh accurately not less than 20 Diazepam
Tablets and make fine powder. Transfer an accurately
weighed portion of the powder, equivalent to about 10
mg of Diazepam, add 50 mL of methanol, ultrasonicate
for 5 minutes and shake by mechanical means for 5 minutes. Add methanol to make exactly 100 mL, filter and
use the filtrate as the test solution after discarding the
first filtrate. Separately, dissolve accurately about 50 mg
of Diazepam RS in methanol to make exactly 100 mL
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and measure,
AT and AS , of the peak area of diazepam of the test
C20H29N3O2HCl: 379.92
Dibucaine Hydrochloride, when dried, contains not less
than 98.0% and not more than 101.0% of dibucaine hydrochloride (C20H29N3O2HCl).
Description Dibucaine Hydrochloride is a white crystal or crystalline powder.
Dibucaine Hydrochloride is very soluble in water, in
ethanol or in glacial acetic acid, freely soluble in acetic
anhydride and practically insoluble in ether.
Dibucaine Hydrochloride is hygroscopic.
solutions of Dibucaine Hydrochloride and Dibucaine
Hydrochloride RS in 1 mol/L hydrochloric acid TS (1 in
(2) Determine the infrared spectra of Dibucaine Hydrochloride and Dibucaine Hydrochloride RS, previously
(3) A solution of Dibucaine Hydrochloride (1 in 10)
Melting Point Between 95 C and 100 C. Charge Dibucaine Hydrochloride into a capillary tube for melting
point determination and dry in vacuum over P2O5 at 80
C for 5 hours. Seal immediately the open end of the
tube and determine the melting point.
pH Dissolve 1.0 g of Dibucaine Hydrochloride in 50
6.0.
Purity
(1) Clarity and color of solution Dissolve

1.0 g of Dibucaine Hydrochloride in 20 mL of water: the
solution is clear and colorless. Determine the absorbance
of this solution at 430 nm as directed under the Ultraviolet-visible Spectrophotometry, using water as the blank:
it is not more than 0.03.
(2) SulfatePerform the test with 0.30 g of Dibucaine Hydrochloride. Prepare the control solution with
0.056%).
(3) Heavy metalsProceed with 1.0 g of Dibucaine
(4) Related substancesDissolve 0.20 g of Dibucaine Hydrochloride in 5 mL of ethanol and use this solution as the test solution. Pipet 1.0 mL of the test solution and add ethanol to make exactly 20 mL. Pipet 2.0
mL of this solution, add ethanol to make exactly 20 mL
a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, water and
glacial acetic acid (3 : 1 : 1) to a distance of about 10 cm
P2O5, 80 C, 5 hours).
Assay Weigh accurately about 0.3 g of Dibucaine Hydrochloride, previously dried, dissolve in 50 mL of a

= 18.996 mg of C20H29N3O2HCl

tight containers.
Diclofenac Sodium
CH2CO 2Na
Cl
NH
Cl
C14H10Cl2NNaO2: 318.13
Diclofenac Sodium, when dried, contains not less than

98.5% and not more than 101.0% of diclofenac sodium
(C14H10Cl2NNaO2).
Description Diclofenac sodium is a white to pale yellowish white crystal or crystalline powder.
Diclofenac sodium is freely soluble in methanol or in
ethanol, sparingly soluble in water or in glacial acetic acid and practically insoluble in ether.
Diclofenac sodium is hygroscopic.
Identification (1) Take 1 mL of a solution of Diclofenac Sodium in methanol (1 in 250), add 1 mL of nitric
acid: a dark red color is observed.
(2) Perform the test with 5 mg of Diclofenac Sodium
as directed under the Flame Coloration Test (2): a light
green color is observed.
(3) Determine the infrared spectra of Diclofenac Sodium and Diclofenac Sodium RS, previously dried, as directed in the potassium bromide disk method under the
(4) A solution of Diclofenac Sodium (1 in 100) responds to the Qualitative Tests for sodium salt.
Purity (1) Heavy metalsProceed with 2.0 g of Diclofenac Sodium according to Method 2 and perform the
Diclofenac Sodium according to Method 3 and perform
(3) Related substancesDissolve 50 mg of Diclofenac Sodium in 50 mL of the mobile phase and use this
solution as the test solution. Pipet 2.0 mL of the test solution and add the mobile phase to make exactly 50 mL.
Pipet 5.0 mL of this solution, add the mobile phase to
the Liquid Chromatography under the following operating conditions. Measure each peak area of these solutions
by the automatic integration method: the area of peak
other than the peak of diclofenac from the test solution is
not larger than that of the standard solution.
Column: A stainless steel column, about 4.6mm in
about 40 C.
glacial acetic acid (3 in 2500) (4 : 3).
KP 9 289
time of diclofenac is about 20 minutes.
System suitability
System performance: Dissolve 35 mg of ethyl parahydroxybenzoate and 50 mg of propyl parahydroxybenzoate in 100 mL of the mobile phase. Take 1 mL of
this solution, add the mobile phase to make exactly 50
mL. When the procedure is run with 20 L of this solution, as directed under the above operating conditions,
ethyl parahydroxybenzoate and propyl parahydroxybenzoate are eluted in this order with the resolution between
under the above operating conditions, the relative standard deviation of peak area of Diclofenac is not more
than 2.0%.
the retention time of diclofenac beginning after the solvent peak.
hours).
Assay Weigh accurately about 0.5 g of Diclofenac Sodium, previously dried, dissolve in 40 mL of water in a
separatory funnel, add 2.0 mL of dilute hydrochloric acid
and extract with 50 mL of chloroform. Extract again with
two 20 mL volumes of chloroform and filter the extract
each time through a pledget of absorbent cotton, moistened with chloroform. Wash the tip of the separatory
funnel and the absorbent cotton, with 15 mL of chloroform, combine the washing with the extracts, add 10.0
mL of a solution of 1 mol/L hydrochloric acid TS in dehydrated ethanol (1 in 100) and titrate with 0.1 mol/L potassium hydroxide-ethanol VS from the first equivalent
point to the second equivalent point (potentiometric titration, Endpoint Detection Method in Titrimetry).

= 31.813 mg of C14H10Cl2NNaO2
Diclofenamide
NH2
O
O
Cl
S
Cl
NH2
C6H6Cl2N2O4S2: 305.16
Diclofenamide, when dried, contains not less than 98.0%
and not more

(C6H6Cl2N2O4S2).
than
101.0%
of
diclofenamide
Description Diclofenamide is a white, crystalline

powder.
Diclofenamide is very soluble in dimethylformamide, soluble in ethanol, slightly soluble in ether and very
slightly soluble in water.
Diclofenamide dissolves in sodium hydroxide TS.
Identification (1) Dissolve 10 mg each of Diclofenamide and Diclofenamide RS in 100 mL each of 0.01
mol/L sodium hydroxide TS. To 10 mL each of these solutions, add 0.1 mL each of hydrochloric acid and determine the absorption spectra of these solutions as directed
same wavelengths.
(2) Determine the infrared absorption spectra of Diclofenamide and Diclofenamide RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Melting Point
Purity (1) ChlorideDissolve 0.10 g of Diclofenamide in 10 mL of dimethylformamide and add 6 mL of

dilute nitric acid and water to make 50 mL. Perform the
control solution as follows: to 0.45 mL of 0.01 mol/L
hydrochloric acid VS, add 10 mL of dimethylformamide,
6 mL of dilute nitric acid and water to make 50 mL (not
more than 0.160%).
(2) SeleniumTake 0.10 g of Diclofenamide, add
0.5 mL of a mixture of perchloric acid and sulfuric acid
(1 : 1) and 2 mL of nitric acid and heat in a water-batch
until no more brown gas evolves and the solution becomes to be a pale yellow clear solution. After cooling,
add 4 mL of nitric acid to this solution, then add water to
make exactly 50 mL and use this solution as the test solution. Separately, pipet 3 mL of Standard Selenium Solution, add 0.5 mL of a mixture of perchloric acid and
sulfuric acid (1 : 1) and 6 mL of nitric acid, then add water to make exactly 50 mL and use this solution as the
and the standard solution as directed under the Atomic
Absorption Specctrophotometry according to the following conditions and determine constant absorbance, AT
and AS, obtained on a recorder after rapid increasing of
the absorption: AT is smaller than AS (not more than 30
ppm). Perform the test by using a hydride generating system and a thermal absorption cell.
Lamp: A selenium hollow cathode lamp
Wavelength: 196.0 nm
Temperature of sample atomizer: When an electric
Furnace is used, about 1000 C
Carrier gas: Nitrogen and argon

(3) Heavy metalsProceed with 2.0 g of Diclofenamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(4) Related substancesDissolve 0.10 g of Diclofenamide in 50 mL of the mobile phase and use this solution as the test solution. Pipet 2.0 mL of the test solution,
add the mobile phase to make exactly 100 mL and use
this solution as the standard solution. Perform 10 L
these solutions by the automatic integration method: the
total area of the peaks other than the peak of diclofenamide from the test solution is not larger than the peak
area of diclofenamide from the standard solution.
Detector, column, column temperature, mobile phase
and flow rate: Proceed as directed in the operating conditions under Assay.
System suitability
Test for required detection: To exactly 5 mL of the
standard solution add the mobile phase to make exactly
100 mL. Confirm that the peak area of diclofenamide obtained from 10 L of this solution is equivalent to 3.5 to
6.5% of that of diclofenamide obtained from 10 L of
above operating conditions, the relative standard deviation of the peak area of diclofenamide is not more than
1.0%.
as the retention time of diclofenamide.
Loss on Drying Not more than 1.0% (1 g, at a pressure
not exceeding 0.67 kPa, 100 C, 5 hours).
Residue on Ignition
Assay Weigh accurately about 50 mg each of Diclofenamide and Diclofenamide RS, previously dried and dissolve in 30 mL each of the mobile phase. To each solution, add exactly 10 mL of the internal standard solution
and the mobile phase to make 50 mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the test
Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS of the peak
area of diclofenamide to that of the internal standard for
Amount (mg) of diclofenamide (C6H6Cl2N2O4S2 )

QT
= amount (mg) of Diclofenamide RS Q
S
Internal standard solutionA solution of butyl para-
hydroxybenzoate in the mobile phase (3 in 5000).
Column: A stainless steel column, about 4 mm in inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 m
about 25 C.
Mobile phase: A mixture of sodium phosphate TS
and acetonitrile (1 : 1).
time of diclofenamide is about 7 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, diclofenamide and the internal standard are eluted in this order with the resolution between
above operating conditions, the relative standard deviation of the ratios of the peak area of diclofenamide to that
of the internal standard is not more than 1.0%.
Diclofenamide Tablets
Diclofenamide Tablets contain not less than 92.0% and
not more than 108.0% of the labeled amount of diclofenamide (C6H6Cl2N2O4S2: 305.16).
Method of Preparation Prepare as directed under Tablets, with Diclofenamide.
Identification (1) Weigh a portion of Diclofenamide
Tablets, previously powdered, equivalent to 0.2 g of Diclofenamide according to the labeled amount, add 20 mL
of methanol, shake and filter. Evaporate the filtrate on a
water-bath to dryness. Dissolve 10 mg of the residue in
100 mL of 0.01 mol/L sodium hydroxide TS. To 10 mL
of this solution, add 0.1 mL of hydrochloric acid and determine the absorption spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry: it
exhibits maxima between 284 nm and 288 nm and between 293 nm and 297 nm.
Dissolution Test Take 1 tablet of Diclofenamide Tablets and perform the test using 900 mL of water as a dissolution solution at 50 revolutions per minute as directed
in the Method 2 under the Dissolution Test. After 60 minutes from the start of the test, take 20 mL or more of the
dissolved solution and filter through a membrane filter
with pore size of not more than 0.8 m. Discard the first
KP 9 291
10 mL of the filtrate, use the subsequent solution as the
of Diclofenamide RS, previously dried at a pressure not
exceeding 0.67 kPa at 100 C for 5 hours, dissolve in 10
mL of ethanol and add water to make exactly 100 mL.
Pipet 10.0 mL of this solution, add water to make exactly
Measure the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 285 nm as
directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Diclofenamide Tablets in 60 minutes is not less than 70.0%.
of diclofenamide (C6H6Cl2N2O4S2)
= WS
AT
1
90
AS C
WS : Amount (mg) of Diclofenamide RS,

C: Labeled amount (mg) of diclofenamide
(C6H6Cl2N2O4S2) in 1 tablet.

tablets of Diclofenamide Tablets. Weigh accurately a portion of the powder, equivalent to about 50 mg of diclofenamide (C6H6Cl2N2O4S2), add exactly 25 mL of the mobile phase and shake for 15 minutes and centrifuge. Pipet
10.0 mL of the supernatant, add 4.0 mL of the internal
standard solution and the mobile phase to make exactly
20 mL and use this solution as the test solution. Separately, weigh accurately about 50 mg of Diclofenamide RS,
previously dried at 100 C at a pressure not exceeding
0.67 kPa for 5 hours, dissolve in 30 mL of the mobile
phase, add 10.0 mL of the internal standard solution and
the mobile phase to make exactly 50 mL and use this solution as the standard solution. Proceed as directed in the
Assay under Diclofenamide.
Amount (mg) of diclofenamide (C6Cl2N2O4S2)

= amount (mg) of Diclofenamide RS QT
QS
Internal standard solutionA solution of butyl parahydroxybenzoate in the mobile phase (3 in 5000).
Dicloxacillin Sodium Hydrate

O
NaO
Cl
O
N
CH3
Cl
N
H
N
O
CH3
S
H
CH3
. H2O
C19H16Cl2N3NaO5SH2O: 510.32
Dicloxacillin Sodium Hydrate contains not less than 850
g (potency) per mg of dicloxacillin (C19H16Cl2N3
NaO5S : 470.33), calculated on the anhydrous basis
Description Dicloxacillin Sodium Hydrate is a white
to light yellowish white crystalline powder.
Dicloxacillin Sodium Hydrate is freely soluble in water
and in methanol, soluble in ethanol, and practically insoluble in ether.
Identification (1) Dissolve 0.125 g of Dicloxacillin
Sodium Hydrate in 5 mL of water, and add diluted hydrochloric acid to make the solution acidic, and extract
with 5 mL of chloroform. Take the chloroform layer, dry
without heating, add 2 mg of disodium chromotropate
o
dehydrate and 2 mL of sulfuric acid and heat to 150 C

in oil bath with shaking: a light yellow color develops at
first and the color turns to purple after 2 or 3 minutes.
(2) Determine the infrared spectra of Dicloxacillin
Sodium Hydrate and Dicloxacillin Sodium Hydrate RS,
the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) The solution of Dicloxacillin Sodium Hydrate responds to the Qualitative test 1) for sodium salt.
of Dicloxacillin Sodium Hydrate in 10 mL of water is
Sterility Test It meets the requirement, when Dicloxacillin Sodium Hydrate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Dicloxacillin Sodium Hydrate is used in a sterile preparation.
Weigh appropriate amount of Dicloxacillin Sodium Hydrate, dissolve in Isotonic Sodium Chloride Injection,
make the solution so that each mL contains 20 mg (potency), and use the solution as the test solution. The
Assay
Weigh accurately an amount of Dicloxacillin

Sodium Hydrate, dissolve in 1 % phosphate buffer, pH
6.0 to make the solution containing 1 mg (potency) dicloxacillin per mL and use the solution as the test solution.
Separately, weigh accurately an amount of Dicloxacillin
Sodium Hydrate RS, dissolve 1 % phosphate buffer, pH
6.0 to make the solution so that each mL contains 1 mg
(potency) and use the solution as the standard solution.
Keep the standard solution at not exceeding 5 C and use
within 7 days. Pipet exactly 1 mL of each of the test solution and the standard solution in iodine bottle, add exactly 2 mL of 1 mol/L sodium hydroxide TS, stand for 15
minutes, add 2 mL of diluted hydrochloric acid (1 in 10)
and 10.0 mL of 0.01 mol/L iodine solution, stand for 15
minutes, if necessary, add 5 mL of carbon tetrachloride ,
mix with shaking, titrate the test solution and the standard solution with 0.01 mol/L sodium thiosulfate by using microburet (indicator: if necessary, 0.2 ~ 0.5 mL of
starch TS), and determine the consumed volume (mL) of
0.01 mol/L of iodine solution, VT and VS . Separately,
add exactly 10 mL of 0.01 mol/L iodine solution to the
test solution and the standard solution, perform a blank
determination without 15 minutes standing and make any
Amount [g (potency)] of dicloxacillin sodium
(C19H16Cl2N3NaO5S)
= Amount [g (potency)] of Dicloxacillin Sodium Hydrate RS
VT
VS
Dicyclomine Hydrochloride
CH2CH3
O
CH2CH2N
Melting Point
pH Dissolve 1.0 g of Dicyclomine Hydrochloride in

and 5.5.
Purify Sulfate Perform the test with 0.5 g of Dicyclomine Hydrochloride and use this solution as the test solution. The color of the test solution is not stronger than
that of the control solution D.
hours).
Assay Weigh accurately about 0.6 g of Dicyclomine
Hydrochloride, dissolve in 70 mL of glacial acetic acid,
add 10 mL of mercuric acetate TS and titrate with 0.1
mol/L perchloric acid VS until blue color develops (indicator: 1 drop of methylosanyl chloride TS). Perform a

Packaging and Storage Preserve in well-closed container.
Diethylcarbamazine Citrate
O
C
cipitate is formed. The precipitate does not dissolve in

nitric acid and dissolves excessive amount of ammonia
TS.
(2) Determine the infrared spectra of Dicyclomine
Hydrochloride and Dicyclomine Hydrochloride RS as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibits similar
HCl
CH2CH3
O
C
N(CH2CH3)2
CH2CO2H
N
HO
C19H35NO2HCl: 345.95
N
Dicyclomine Hydrochloride contains not less than 99.0%

and not more than 102.0% of dicyclomine hydrochloride
(C19H35NO2HCl), calculated on the anhydrous basis.
Description Dicyclomine Hydrochloride is a white
fine crystalline powder, is odorless and has a bitter taste.
Dicyclomine Hydrochloride is freely soluble in ethanol
or in chloroform, soluble in water and very slightly soluble in ether.
Identification (1) Take 5 mL of a solution of Dicyclomine Hydrochloride (1 in 500) and add 2 mL of 2 mol/L
nitric acid TS and 2 mL of silver nitrate TS: a white pre-
CO2H
CH2CO2H
CH3
C10H21N3OC6H8O7: 391.42
Diethylcarbamazine Citrate, when dried, contains not
less than 98.0% and not more than 101.0% of diethylcarbamazine citrate (C10H21N3OC6H8O7).
Description Diethylcarbamazine Citrate is a white,
crystalline powder, is odorless and has an acid and bitter
taste.
Diethylcarbamazine Citrate is very soluble in water, soluble in ethanol and practically insoluble in acetone, in
KP 9 293
chloroform or in ether.
A solution of Diethylcarbamazine Citrate (1 in 20) is
acidic.
Diethylcarbamazine Citrate is hygroscopic.
Identification (1) Dissolve 0.5 g of Diethylcarbamazine Citrate in 2 mL of water, add 10 mL of sodium hydroxide TS and extract with four 5 mL volumes of chloroform. Wash the combined chloroform extracts with 10
mL of water and evaporate chloroform on a water-bath
and add 1 mL of ethyl iodide to the residue and boil gently with the aid of a reflux condenser for 5 minutes. Evaporate excess amount of ethyl iodide through air and add
4 mL of ethanol. Cool the ethanol solution in an ice-bath
with continuous stirring, add ether until precipitates are
produced and stir until crystallization is evident. Allow to
stand in the ice-bath for 30 minutes and collect the precipitate. Dissolve the precipitate in 4 mL of ethanol, repeat
the recrystallization in the same manner and then dry at
105 C for 4 hours: the melting point is between 151 C
and 155 C.
(2) Neutralize the residue after extracting with chloroform in (1) with dilute hydrochloric acid: the solution
responds to the Qualitative Tests (2) and (3) for citrate.
Melting Point
Between 135.5 C and 138.5 C.
Purity Heavy metalsProceed with 2.0 g of Diethylcarbamazine Citrate according to Method 4 and perform
hours).
Assay Weigh accurately about 0.75 g of Diethylcarbamazine Citrate, previously dried, dissolve in 50 mL of
glacial acetic acid by warming, cool and titrate with 0.1

= 39.142 mg of C10H21N3OC6H8O7
Method of Preparation Prepare as directed under Tablets, with Diethylcarbamazine Citrate.

Identification (1) Take a portion of powdered Diethylcarbamazine Citrate Tablets, equivalent to 0.5 g of Diethylcarbamazine Citrate, according to the labeled amount,
add 10 mL of water, shake, and filter. Add 10 mL of sodium hydroxide TS to the filtrate, and proceed as directed in the Identification (1) under Diethylcarbamazine
Citrate.
(2) Take a portion of powdered Diethylcarbamazine
Citrate Tablets, equivalent to 0.8 g of Diethylcarbamazine Citrate according to the labeled amount, add 10 mL
of water, shake, centrifuge, and filter the supernatant liquid. To 5 mL of the filtrate, add 5 mL of sodium hydroxide TS, and extract with two 20 mL volumes of chloroform. Separate the aqueous layer, and neutralize with dilute hydrochloric acid: the solution responds to the Qualitative Tests (2) and (3) for citrate.
Assay Weigh accurately not less than 20 Diethylcarbamazine Citrate Tablets and powder. Weigh accurately a
portion of the powder, equivalent to about 50 mg of diethylcarbamazine citrate (C10H21N3OC6H8O7), add 10 mL
of water, shake well, add 5 mL of sodium hydroxide TS,
then add exactly 20 mL of the internal standard solution,
and shake vigorously for 10 minutes. Centrifuge, discard
the aqueous layer, and use the chloroform layer as the
test solution. Separately, weigh accurately 50 mg of Diethylcarbamazine Citrate RS, previously dried at 105 C
for 4 hours, dissolve in 10 mL of water, add 5 mL of sodium hydroxide TS, proceed in the same manner as the
preparation of the test solution, and use the chloroform
layer as the standard solution. Perform the test with 2 L
each of the test solution and the standard solution as directed under the Gas Chromatography according to the
following conditions, and calculate the ratios, QT and
QS , of the peak area of diethylcarbamazine to that of the

internal standard for the test solution and the standard solution, respectively.
Amount (mg) of diethylcarbamazine citrate
(C10H21N3OC6H8O7) = amount (mg) of
Diethylcarbamazine Citrate RS QT
Diethylcarbamazine Citrate
Tablets
Diethylcarbamazine Citrate Tablets contain not less than
of diethylcarbamazine citrate (C10H21N3OC6H8O7:
391.42).
QS
Internal standard solutionA solution of noctadecane in chloroform (1 in 1250).

Column: A glass tube, 3 mm in inside diameter and 1
to 2 m in length, having 35% methylphenyl silicone po-

lymer coated at the ratio of 3.0 percent on silanized siliceous earth for gas chromatography (180 m to 250 m
about 145 C.
time of the internal standard is 8 to 11 minutes.
Selection of column: Proceed with 2 L of the standard solution under the above operating conditions and
use a column from which diethylcarbamazine and the internal standard are eluted in this order with a resolution
between their peaks being not less than 5.0.
Difenidol Hydrochloride
CH2CH2CH2COH
HCl
C21H27NOHCl: 345.91
Difenidol Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of difenidol hydrochloride (C21H27NOHCl).
Description Difenidol Hydrochloride is a white crystal
or crystalline powder and is odorless.
Difenidol Hydrochloride is freely soluble in methanol,
soluble in ethanol, sparingly soluble in water or in glacial
acetic acid and practically insoluble in ether.
Identification (1) Dissolve 10 mg of Difenidol Hydrochloride in 1 mL of sulfuric acid: an orange-red color
is observed. Take this solution, add carefully 3 drops of
water: the solution becomes yellowish brown and colorless on the addition of 10 mL of water.
(2) Take 5 mL of a solution of Difenidol Hydrochloride (1 in 100) and add 2 mL of Reinecke salt TS: a light
red precipitate is produced.
(3) Take 10 mL of a solution of Difenidol Hydrochloride (1 in 100) and add 2 mL of sodium hydroxide TS
and extract with two 15 mL volumes of chloroform.
Combine the extracts, wash with three 10 mL volumes of
water, evaporate the chloroform on a water-bath and dry
the residue in a desiccator (in vacuum, silica gel, 55 C)
for 5 hours: the residue melts between 103 C and 106
C.
(4) A solution of Difenidol Hydrochloride (1 in 100)

pH Dissolve 1.0 g of Difenidol Hydrochloride in 100
mL of freshly boiled and cooled water: the pH of this solution is between 4.7 and 6.5.
g of Difenidol Hydrochloride in 10 mL of methanol: the
(2) Heavy metalsProceed with 1.0 g of Difenidol
Difenidol Hydrochloride according to Method 3 and perform the test (not more than 1 ppm).
(4) Related substancesDissolve 0.10 g of Difenidol Hydrochloride in methanol to make exactly 10 mL
and use this solution as the test solution. Separately, dissolve 10 mg of 1,1-diphenyl-4-piperidino-1-butene hydrochloride RS in methanol to make exactly 20 mL, pipet 1.0 mL of this solution, add methanol to make exactly 10 mL and use this solution as the standard solution.
Perform the test with the test solution and the test solution as directed under the Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solution on a plate of silica gel with a fluorescent indicator
mixture of toluene, methanol and glacial acetic acid (10 :
solution.
Assay Weigh accurately about 0.35 g of Difenidol Hydrochloride, previously dried, dissolve in 30 mL of glacial acetic acid by warming, if necessary, cool, add 30
mL of acetic anhydride and titrate with 0.05 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

KP 9 295
Diflucortolone Valerate
O
O
CH3
O
CH3
HO
spherical octadecylsilanized silica gel for liquid chromatography (3 m in particle diameter).

(50:50).
Time span of measurement: Twice the retention time
of diflucortolone valerate peak.
H
H
CH3

hours).
CH3
O
F
C27H36F2O5: 478.57
Diflucortolone Valerate contains not less than 97.0% and
not more than 102.0% of diflucortolone valerate
(C27H36F2O5), calculated on the dried basis.
Description Diflucortolone Valerate is a white crystalline powder.
Diflucortolone Valerate is freely soluble in dichloromethane or in dioxin, sparingly soluble in ether, slightly soluble in methanol, and practically insoluble in water.
Identification Determine the absorption spectra of solutions of Diflucortolone Valerate and Diflucortolone
Valerate RS in methanol (1 in 50000) as directed under
Assay Weigh accurately 30 mg each of Diflucortolone

Valerate and Diflucortolone Valerate RS, add a mixture
of acetonitrile and water (75 : 25) to make exactly 100
mL each and use these solutions as the test solution and
to the operating conditions in the Related substances under the Purity and determine the area of the peak for diflucortolone valerate in the test solution, AT , and in the
standard solution, AS .
Amount (mg) of diflucortolone valerate (C27H36F2O5)

tight containers.
Digitoxin

D : Between +98 and
+103 (0.2 g, after drying, dioxane, 20 mL, 100 mm).
Purity Related substancesWeigh 60 mg of Diflucortolone Valerate, add a mixture of acetonitrile and water
(75 : 25) to make exactly 100 mL and use this solution as
the test solution. Pipet exactly 1 mL of the test solution,
add a mixture of acetonitrile and water (75 : 25) to make
exactly 100 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and determine the area of the peaks in
these solutions by the automatic integration method: the
area of each peak other than the principal peak obtained
from the test solution is not more than the area of the
principal peak obtained from the standard solution (1%)
and total area of the peaks other than the principal peak
from the test solution is not more than twice the area of
the principal peak from the standard solution (2%).
AT
AS
= amount (mg) of Diflucortolone Valerate RS
O
O
CH3
CH3
H
H
CH3
O
OH
O
H
H
H
CH3
O
O
OH
H
H
CH3
O
O
OH
H
H
H
HO
OH
C41H64O13: 764.94
Digitoxin, when dried, contains not less than 90.0% and
not more than 101.0% of digitoxin (C41H64O13).
Description Digitoxin is a white to pale yellowish
white, crystalline powder and is odorless.

Digitoxin is soluble in chloroform, sparingly soluble in
methanol or in ethanol and practically insoluble in water
or in ether.
culate the ratios, QT and QS of the peak area of digitoxin

to that of the internal standard for the test solution and
Identification (1) Transfer 1 mg of Digitoxin to a

small test tube about 10 mm in inside diameter, dissolve
in 1 mL of a solution of ferric chloride in glacial acetic
acid (1 in 10000) and underlay gently with 1 mL of sulfuric acid: at the zone of contact of the two liquids, a
brown ring free from a reddish color is observed and the
color of the upper layer near the contact zone changes to
green through purple. Finally the color of the entire glacial acetic acid layer changes to green through deep blue.
(2) Take 2 mg of Digitoxin, add 25 mL of a freshly
prepared solution of m-dinitrobenzene in ethanol (1 in
100) and dissolve by shaking. Pipet 2 mL of this solution,
add 2 mL of a solution of tetramethylammonium hydroxide in ethanol (1 in 200) and mix: a red-purple color is
observed slowly and then fades.
(3) Dissolve 1 mg each of Digitoxin and Digitoxin
RS in a mixture of chloroform and ethanol (1 : 1) to
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, methanol
air-dry the plate. Spray evenly dilute sulfuric acid upon
the plate and heat at 110 C for 10 minutes: the spot from
the test solution shows the same Rf value as the spot
Amount (mg) of digitoxin (C41H64O13)

18 (after drying, 0.50 g, chloroform, 20 mL, 200 mm).
Purity DigitoninDissolve 10 mg of Digitoxin in 2
mL of ethanol in a test tube having the inner walls which
are free from scratches, add 2 mL of a solution of cholesterol in ethanol (1 in 200), mix gently and allow to stand
for 10 minutes: no turbidity is produced.
100 C, 2 hours).
= amount (mg) of Digitoxin RS
QT
QS
Internal standard solutionA solution of acenaphthene in methanol (3 in 1000000).

Column: A stainless steel column, about 4 mm in inside diameter and about 15 cm to 20 cm in length,
chromatography (5 m in particle diameter).
1).
time of digitoxin is about 5 minutes.
Selection of column: Proceed with 50 L of the standard solution according to the above conditions, use a
column givion elution of digitoxin and the internal standard in this order with a resolution between their peaks
tight containers.
Digitoxin Injection
Digitoxin Injection is an aqueous solution for injection.
Digitoxin Injection contains not less than 90.0% and not
more than 110.0% of the labeled amount of digitoxin
(C41H64O13: 764.95).
Method of Preparation Prepare as directed under Injections, with a solution of Digitoxin in 5 to 50 % ethanol.
Digitoxin Injection is a clear, colorless
Description
liquid.
Assay Dissolve about 20 mg each of Digitoxin and Digitoxin RS, previously dried and accurately weighed, in
methanol to make exactly 200 mL. Pipet 5.0 mL each of
these solutions, add 10.0 mL of the internal standard solution to each solution, add 12.5 mL of water, then add
methanol to make 50 mL and use these solutions as the
test solution and the standard solution, respectively. Perform the test with 50 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following conditions and cal-
Identification (1) Take a portion of Digitoxin Injection,

equivalent to 1 mg of Digitoxin according to the labeled
amount and add 10 mL of water and extract with 10 mL
of chloroform. Evaporate the chloroform extract to dryness on a water-bath. Proceed with the residue as directed in the Identification (1) under Digitoxin.
(2) Take a portion of Digitoxin Injection, equivalent
to 0.2 mg of Digitoxin according to the labeled amount
and add 10 mL of water and extract with 10 mL of chloroform. Evaporate the chloroform extract on a water-bath
KP 9 297
with the aid of a current of air to dryness. Add 10 mL of
a freshly prepared m-dinitrobenzene in ethanol (1 in 100)
and dissolve by shaking. Proceed with 2 mL of this solution as directed in the Identification (2) under Digitoxin.
(3) Retention time of the principal peak in the chromatogram of the test solution under the Assay corresponds to that of the standard solution.
Sterility Test

Digitoxin.
It

Assay Take accurately a volume of Digitoxin Injection,
equivalent to about 0.5 mg of Digitoxin, add 10 mL of
the internal standard solution, mix, add methanol to
make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately about 10 mg of Digitoxin RS, previously dried at 100 C under vacuum for 2
hours, dissolve in methanol to make exactly 100 mL. Pipet 5 mL of the solution, add 10 mL of the internal standard solution and methanol to make exactly 50 mL. Use
this solution as the standard solution. Perform the test as
directed in the Assay under Digitoxin.
Amount (g/mL) of digitoxin (C41H64O13)

= Amount of Digitoxin RS (mg)
QT
QS
0.05
Internal standard solutionAcenaphthene in methanol (3 in 1000000).

Digitoxin Tablets
Digitoxin Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of digitoxin
(C41H64O13: 764.95).
Method of Preparation Prepare as directed under Tablets, with Digitoxin.
Identification (1) Weigh a portion of Digitoxin Tablets,
previously powdered, equivalent to 2 mg of digitoxin
(C41H64O13) according to the labeled amount, place in a
separatory funnel, shake with 30 mL of water and shake

vigorously with 30 mL of chloroform. Filter the chloroform extract with a funnel on which a small amount of
anhydrous sodium sulfate is placed and transfer to a
round-bottomed flask connected by a universal joint.
Evaporate the solution to dryness by warming under reduced pressure and dissolve the residue in 10 mL of
chloroform. Transfer 5 mL of this solution to a small test
tube about 10 mm in inside diameter and evaporate to
dryness on a water-bath with the aid of a current of air.
Proceed with the residue as directed in the Identification
(1) under Digitoxin.
(2) Evaporate 4 mL of the chloroform solution obtained in (1) to dryness, by warming under reduced pressure, add 10 mL of freshly prepared solution of mdinitrobenzene in ethanol (1 in 100) to the residue and
dissolve by shaking. When the procedure is run with 2
under Digitoxin.
Dissolution Test Take 1 tablet of Digitoxin Tablets and
perform the test using 500 mL of diluted hydrochloric
acid (3 in 500), degassed by a suitable method, as dissolution solution at 100 revolutions per minute as directed
in the Method 1 under the Dissolution Test. After 30 minutes from the start of the test, take a + 15 mL of the dissolved solution and immediately add the same volume of
fresh test solution, previously warmed at 37 0.5 C, to
the vessel carefully. Filter a + 15 mL of the dissolved solution through a membrane filter (less than 0.8 m in
pore size). Discard the first 10 mL of the filtrate and use
the subsequent filtrate as the test solution. Pipet exactly a
mL of the test solution, equivalent to about 2 g of Digitoxin (C41H64O13) according to the labeled amount, transfer to a glass-stoppered centrifuge tube T30 and warm at
37 0.5 C for 30 minutes. Further, after 60 minutes
from the start the test, take a + 15 mL of the dissolved
solution, proceed in the same manner, pipet exactly a mL
of the test solution and transfer to a glass-stoppered centrifuge tube T60. Separately, weigh accurately 100 times
the labeled amount of digitoxin RS, previously dried under reduced pressure at 100 C for 2 hours and dissolve
in ethanol to make exactly 100 mL. Pipet 1.0 mL of this
solution, add the test solution to make exactly 500 mL,
warm at 37 0.5 C for 60 minutes and filter through a
membrane filter (less than 0.8 m in pore size). Discard
the first 10 mL of the filtrate and use the subsequent filtrate as the standard solution. Pipet exactly a mL each of
the standard solution and the test solution, transfer to
glass-stoppered centrifuge tubes, TS Tand TB , respectively. Add exactly 7 mL of chloroform to each of the
glass-stoppered centrifuge tubes, T30 , T60 , TS and
TB , shake vigorously for 10 minutes and centrifuge. Discard the aqueous layer, pipet 5.0 mL of the chloroform
layer, transfer to brown test tubes T '30 , T'60 , T 'S and
T 'B , evaporate the chloroform, add exactly 4 mL each of

0.05 g/dL ascorbic acid-hydrochloric acid TS, shake well
and allow to stand for 10 minutes. Then add exactly 0.5
mL each of dilute hydrogen peroxide TS, shake well and
allow to stand at a constant temperature between 25 C
and 30 C for 45 minutes. Determine the fluorescence intensities, F30 , F60 , FS and FB , of these solutions at
about 395 nm of the excitation wavelength and at about
560 nm of the fluorescence wavelength as directed under
the Fluorometry.
Dissolution rates of Digitoxin Tablets after 30 minutes
and 60 minutes are not less than 60.0% and 85.0%, respectively.
No retest requirement is applied to Digitoxin Tablets.
of digitoxin (C41H64O13) for 30 minutes
= WS
F30 F B 1
FS F B C
FS F B
FS F B
FS and FB , of the test solution, standard solution and

the diluted ethanol, respectively, at 400 nm of the excitation wavelength and at about 570 nm of the fluorescence
wavelength as directed under the Fluorometry.
Amount (mg) of digitoxin (C41H64O13)
= amount (mg) of Digitoxin RS

of digitoxin (C41H64O13) for 60 minutes
F 60 F B F30 F B + 15
1
=
WS (
ethanol (4 in 5) to make exactly 100 mL and use this solution as the standard solution. Pipet 2.0 mL each of the
test solution, the standard solution and the diluted ethanol (4 in 5) into brown glass-stoppered test tubes T, S
and B, respectively. Add exactly 10 mL each of 0.2
mg/mL ascorbic acid-hydrochloric acid TS, shake well
and immediately add exactly 1 mL each of dilute hydrogen peroxide TS. Shake vigorously and allow to stand at
a constant temperature between 25 C and 30 C for 45
minutes. Determine the fluorescence intensities, FT ,
500
WS : Amount (mg) of Digitoxin RS

C: Labeled amount (mg) of digitoxin (C41H64O13) in 1
tablet
a +15: Measured volume (mL) of dissolved solution at
the specified time.
to the following method. Transfer 1 tablet of Digitoxin
Tablets to a 50-mL beaker, add 0.5 mL of water to disintegrate the tablet, add 5 mL of acetonitrile and warm in a
water-bath for 5 minutes, covering the beaker with a
watch glass. After cooling, transfer the solution to separatory funnel A, rinse the beaker with 30 mL of chloroform and then with 20 mL of water, then transfer rinsings
of the beaker to separatory funnel A, shake well and extract. Transfer the extract to separatory funnel B containing 5 mL of a solution of sodium bicarbonate (1 in 100)
and shake to wash. Filter the chloroform layer through a
pledget of absorbent cotton, previously moistened with
chloroform. Extract the water layer in separator A with
two 30 mL volumes of chloroform, wash the chloroform
extract with a solution of sodium bicarbonate (1 in 100)
in separator B, filter in the same manner and combine the
filtrate with the first one. Evaporate this filtrate to dryness under reduced pressure by warming, add diluted
ethanol (4 in 5) to make exactly V mL of a solution to
contain 5 g of digitoxin (C41H64O13) per mL. Shake vigorously for 20 minutes to dissolve and use this solution
10 mg of Digitoxin RS, previously dried at 100 C for 2
hours and dissolve in diluted ethanol (4 in 5) to make exactly 100 mL. Pipet 5.0 mL of this solution, add diluted
FT F B
V
FS F B 2000
Assay Weigh accurately not less than 20 Digitoxin

Tablets and powder. Weigh accurately a portion of the
powder, equivalent to about 0.5 mg of digitoxin
(C41H64O13) and shake with 12.5 mL of water for 10 minutes. Add exactly 10 mL of the internal standard solution, shake for 20 minutes and add methanol to make 50
mL. Centrifuge this solution and use the supernatant as
mg of Digitoxin RS, previously dried in vacuum at 100
C for 2 hours, dissolve in methanol to make exactly 200
mL. Pipet 5.0 mL of the solution, add 10.0 mL of the internal standard solution and 12.5 mL of water, then methanol to make 50 mL and use this solution as the standard solution. Proceed as directed in the Assay under Digitoxin.
Amount (mg/mL) of digitoxin (C41H64O13)

= amount (mg) of Digitoxin RS QT 0.025
QS
Internal standard solutionA solution of acenaphthene in methanol (3 in 1000000).

tight containers.
KP 9 299
Digoxin
O
O
HO
H
CH3
OH
O
H
H
H
CH3
O
H
H
CH3
CH3
( AS ) solutions. AT is not larger than AS , and the total

of the areas of the peaks other than digoxin and gitoxin,
obtained by the area percentage method, is not more than
3%.
O
OH
H
H
CH3
O
O
OH
H
H
H
HO
of this solution, add 10 mL of water, add dilute ethanol to

make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately 5.0 mg of Gitoxin
RS, previously dried under reduced pressure at 105 C
for 1 hour, and add a mixture of acetonitrile and water
(7 : 3) to make exactly 200 mL. Pipet accurately 2 mL of
this solution, add dilute ethanol to make exactly 50 mL
the test with 10 L each of the test solution and standard
solution according to the following condition as directed
under the Liquid Chromatography and determine the
peak are of gitoxin in the test ( AT ) and the standard
OH
C41H64O14: 780.94
Digoxin, when dried, contains not less than 96.0% and
not more than 106.0% of digoxin (C41H64O14).
Description Digoxin is a colorless to white crystal or
white, crystalline powder.
Digoxin is freely soluble in pyridine, slightly soluble in
ethanol, very slightly soluble in glacial acetic acid and
Identification (1) Transfer 1 mg of Digoxin to a small
test tube, about 10 mm in inside diameter, dissolve in 1
mL of a solution of ferric chloride in glacial acetic acid
(1 in 10000) and underlay gently with 1 mL of sulfuric
acid: at the zone of contact of the two liquids, a brown
ring free from a reddish color is observed and the color
of the upper layer near the contact zone changes to green
through purple. Finally the color of the entire glacial
acetic acid layer shows a green color through a deep blue
color.
(2) Determine the infrared spectra of Digoxin and
Digoxin RS, both previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
D : Between + 10.0 and
+ 13.0 (after drying, 0.2 g, pyridine, 10 mL, 100 mm).
0.10 g of Digoxin in 15 mL of diluted ethanol (4 in 5) by
warming: the solution is clear and colorless.
(2) Related substancesWeigh accurately about
25.0 mg of Digoxin, dissolve in 50 mL of warm ethanol,
cool, add ethanol to make exactly 100 mL. Pipet 10 mL
and flow rate: Proceed as directed in the operating conditions in the Assay.
System suitability
Test for required detectability: Pipet accurately 1
mL of the test solution, add the mobile phase to make
exactly 100 mL and use this solution as the solution for
system suitability test. Pipet accurately 1 mL of this solution and add mobile phase to make exactly 10 mL. Confirm that the peak area of digoxin obtained from 10 L of
this solution is equivalent to 7% to 13% of that from the
solution for system suitability test.
System performance: Dissolve 25 mg of Digoxin
in 50 mL of warm ethanol, cool and add ethanol to make
exactly 100 mL. Pipet 10 mL of this solution, add exactly
5 mL of a solution of propyl parahydroxybenzoate in
ethanol (1 in 4000), 10 mL of water and dilute ethanol to
this solution under the above operating conditions, digoxin and propyl p-hydroxybenzoate are eluted in this
less than 5.
times with 10 L each of the solution for system suitability test under the above operating conditions, the relative
standard deviation of the peak area of digoxin is not
more than 1.0%.
105 C, 1 hours).
Assay Weigh accurately about 25 mg each of Digoxin
and Digoxin RS, previously dried, dissolve in 50 mL
each of warm ethanol, cool and add ethanol to make exactly 100 mL each. Pipet accurately 10 mL each of these
solutions, add 5 mL each of the internal standard solution,
add 10 mL each of water and dilute ethanol to make exactly 50 mL each, and use these solutions as the test and

standard solutions, respectively. Perform the test with 10
L each of the test solution and standard solution as directed under the Liquid Chromatography according to
the following conditions and determine the ratios, QT
and QS , of the peak area of digoxin to that of the internal standard for the test and standard solutions, respectively.
Amount (mg) of digoxin (C41H64O14)
= amount (mg) of Digoxin RS QT
QS
Internal standard solutionA solution of propyl phydroxybenzoate in ethanol (1 in 4000)

diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter)
about 30 C.
(7:3).
time of digoxin is about 10 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, digoxin and the internal standard are
above operating conditions, the relative standard deviation of the ratio of the peak area of digoxin to that of the
tight containers.
Digoxin Injection
Digoxin Injection is an aqueous solution for injection.
Digoxin Injection contains not less than 90.0% and not
more than 105.0% of the labeled amount of digoxin
(C41H64O14: 780.94).
Method of Preparation Prepare as directed under Injections, with a solution of Digoxin in 5 to 50 vol% ethanol.
Description Digoxin Injection is a clear, colorless liquid.
Identification Dilute Digitoxin Injection, if necessary,

with ethanol so that each mL contains about 2.5 mg of
Digoxin according to the labeled amount and use this solution as the test solution. Separately, dissolve 0.5 mg of
Digoxin RS in 2 mL of methanol and use this solution as
the standard solution. Perform the test with these solutions as directed under the Thin-layer Chromatography.
Spot 10 L each of the test and the standard solution on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methanol and water (7 : 3)
to a distance of about 10 cm and air-dry the plate. Spray
evenly the plate with a freshly prepared mixture containing one volume of sodium toluenesulfon chloroamide
trihydrate solution (3 in 100) and four volumes of trichloroacetic acid in ethanol (1 in 4), heat at 110 C for 10
minutes and examine the plate under UV light (the principal wavelength of 366 nm). The Rf values of the principal spots obtained from the test solution and the standard solution are not different each other.
Bacterial Endotoxins Less than 200 EU per mg of Digoxin.
It

Assay Transfer an exactly measured volume of Digoxin Injection, equivalent to 2.5 mg of digoxin (C41H64O14),
add 5 mL of the internal standard solution and dilute
ethanol to make 50 mL, and use this solution as the test
Digoxin RS, previously dried under reduced pressure at
105 C for 1 hour, dissolve in 50 mL of warm ethanol,
cool, and add ethanol to make exactly 100 mL. Pipet exactly 10 mL of this solution, add exactly 5 mL of the internal standard solution, 10 mL of water and dilute ethanol to make 50 mL, and use this solution as the standard
solution. Perform the test with 10 L each of the test solution and the standard solution as directed under Liquid
and determine the ratios, QT and QS , of the peak area
of digoxin to that of the internal standard, obtained with

= amount (mg) of Digoxin RS
QT
1
Q S 10
Internal standard solutionA solution of propyl phydroxybenzoate in ethanol (1in 40000).
KP 9 301
about 30 C.
(7:3).
System suitability
Digoxin Tablets
Digoxin Tablets contain not less than 90.0% and not
more than 105.0% of the labeled amount of digoxin
(C41H64O14: 780.94).
Method of Preparation Prepare as directed under Tablets, with Digoxin.
Identification Weigh a portion of powdered Digitoxin
Tablets, equivalent to 0.5 mg of digitoxin (C41H64O13)
according to the labeled amount, add 2 mL of methanol,
shake for 10 mL to mix, filter and use the filtrate as the
test solution. Separately, dissolve 0.5 mg of Digoxin RS
in 2 mL of methanol and use this solution as the standard
under the Thin-layer Chromatography. Spot 10 L each
plate with a mixture of methanol and water (7 : 3) to a
evenly the plate with a freshly prepared mixture containing one volume of sodium toluenesulfon chloroamide
trihydrate solution (3 in 100) and four volumes of trichloroacetic acid in ethanol (1 in 4), heat at 110 C for 10
minutes and examine the plate under UV light (the principal wavelength of 366 nm). The Rf values of the prin-
cipal spots obtained from the test solution and the standard solution are not different each other.
Dissolution Test Take 1 tablet of Digoxin Tablets and
perform the test using 500 mL of diluted hydrochloric
acid (3 in 500) as dissolution solution, at 100 revolutions
per minute, as directed in the Method 1 under the Dissolution Test. After 60 minutes from the start of the test,
take 30 mL or more of the dissolved solution and filter
through a membrane filter (less than 0.8 m in pore size).
Discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, weigh accurately about 25 mg of digoxin RS, previously dried in
vacuum at 105 C for 1 hour, dissolve in a small volume
of ethanol and add a mixture, containing four volumes of
ethanol and one volume of water, to make exactly 500
mL. Pipet 5.0 mL of this solution, add the test solution to
make exactly 500 mL and use this solution as the standard solution. Pipet 2.0 mL each of the test solution, the
standard solution, the dissolution solution and transfer to
brown glass-stoppered test tubes, T, S and B, respectively. Add exactly 10 mL of 0.12 mg/mL ascorbic acidhydrochloric acid TS to each of these solutions and shake.
Immediately add 1.0 mL of dilute hydrogen peroxide TS,
shake well and allow to stand at a constant temperature
between 25 C and 30 C for 45 minutes. Determine the
fluorescence intensities, FT , FS and FB , of the test
solution, standard solution and the dissolution solution,
respectively, at about 360 nm of the excitation wavelength and at 485 nm of the fluorescence wavelength as
directed under the Fluorometry.
The dissolution rate of Digoxin Tablets in 60 minutes is
not less than 65.0%.
No retest requirement is applied to Digoxin Tablets.

of digoxin (C41H64O14) = W S
FT F B 1
FS F B C
WS : Amount (mg) of Digoxin RS,

C: Labeled amount (mg) of digoxin (C41H64O14) in 1
tablet.
to the following method. To 1 tablet of Digoxin Tablets,
add 0.5 mL of water to disintegrate, add exactly 0.5 mL
of the internal standard solution, and add V mL of dilute
ethanol to render the concentration to be about 21 g of
digoxin (C41H64O14) in 1 mL. Exposure this solution to
ultrasonic waves, shake for 5 minutes to mix, filter, and
use the filtrate as the test solution. Separately, weigh accurately about 25 mg of Digoxin RS, previously dried
under reduced pressure at 105 C for 1 hour, dissolve in
50 mL of warm ethanol , cool, and add ethanol to make
exactly 100 mL. Pipet 10 mL of this solution and add
ethanol to make exactly 20 mL. Pipet 1 mL of this solution, add exactly 0.5 mL of the internal standard solution,

add 1.5 mL of water and (V-2) mL of dilute ethanol and
use this as the standard solution. Perform the test with
the test solution and standard solution as directed in the
Assay.
QT
1
Q S 200
Internal standard solutionA solution of propyl phydroxybenzoate in ethanol (1in 40000/V).

Digoxin Tablets. Transfer an accurately weigh a portion
of the powder, equivalent to about 2.5 mg of digoxin
(C41H64O14), add 30 mL of dilute ethanol, exposure to ultrasonic waves for 20 minutes and shake for 5 minutes to
mix. Add exactly 5 mL of the internal standard solution
and dilute ethanol to make 50 mL. Centrifuge the solution and use the supernatant liquid as the test solution.
Separately, weigh accurately about 25 mg of Digoxin RS,
previously dried under reduced pressure at 105 C for 1
hour, dissolve in 50 mL of warm ethanol, cool, and add
ethanol to make exactly 100 mL. Pipet 10 mL of this solution, add exactly 5 mL of the internal standard solution,
10 mL of water and dilute ethanol to make 50 mL, and
solution as directed under Liquid Chromatography according to the following conditions, and determine the
ratios, QT and QS , of the peak area of digoxin to that
of the internal standard, obtained with the test solution

QT
1
Q S 10
Internal standard solutionA solution of propyl phydroxybenzoate in ethanol (1in 40000).

about 30 C.
(7:3).
System suitability


tight containers.
Dihydrocodeine Phosphate
CH3
N
H3PO4
O
CH3O
Hydrocodeine Phosphate
H OH
C18N23NO3H3PO4: 399.38
Dihydrocodeine Phosphate contains not less than 98.0%

and not more than 101.0% of dihydrocodeine phosphate
(C18N23NO3H3PO4), calculated on the dried basis.
Description Dihydrocodeine Phosphate is a white to
yellowish white, crystalline powder.
Dihydrocodeine Phosphate is freely soluble in water or
in glacial acetic acid, slightly soluble in ethanol and
When dissolve 1.0 g of Dihydrocodeine Phosphate in 10
mL of water, the pH of this solution is between 3.0 and
5.0.
Dihydrocodeine Phosphate is affected by light.
solutions of Dihydrocodeine Phosphate and Dihydrocodeine Phosphate RS (1 in 10000) as directed under the
(2) Determine the infrared spectra of Dihydrocodeine
Phosphate and Dihydrocodeine Phosphate RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra
(3) A solution of Dihydrocodeine Phosphate (1 in 20)
responds to the Qualitative Tests (1) for phosphate.
Purity (1) ChloridePerform the test with 0.5 g of
Dihydrocodeine Phosphate. Prepare the control solution
with 0.30 mL of 0.01 mol/L hydrochloric acid (not more
than 0.021%).
(2) SulfatePerform the test with 0.20 g of Dihy-
KP 9 303
drocodeine Phosphate. Prepare the control solution with
1.0 mL of 5 mol/L sulfuric acid (not more than 0.240%).
(3) Related substancesDissolve 0.20 g of Dihydrocodeine Phosphate in 10 mL of diluted ethanol (1 in
of the test solution, add diluted ethanol (1 in 2) to make
exactly 50 mL and use this solution as the standard solution. Perform the test with the test solution and the standard solutions as directed under the Thin-layer Chromatography. Spot 10 L of the test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of dehydrated ethanol, toluene, acetone
and strong ammonia water (14 : 14 : 7 : 1) to a distance
of about 15 cm and air-dry the plate. Examine under ultra-violet light (main wavelength: 254 nm): the spots
more intense than that from the standard solution.
Loss on Drying
hours).
Not more than 1.0% (0.5 g, 105 C, 4
Assay Weigh accurately about 0.5 g of Dihydrocodeine

Phosphate, dissolve in 70 mL of glacial acetic acid and
titrate with 0.1 mol/L perchloric acid VS until the color
of the solution changes from purple through blue to
greenish blue (indicator: 3 drops of methylrosaniline

= 39.938 mg of C18N23NO3H3PO4
tight containers.
10% Dihydrocodeine Phosphate

Powder
10% Hydrocodeine Phosphate Powder
10% Dihydrocodeine Phosphate Powder contains not
less than 9.3% and not more than 10.7% of dihydrocodeine phosphate (C18N23NO3H3PO4: 399.38).
100 g
Lactose Hydarate
To make 1000 g
solution of 10 % Dihydrocodeine Phosphate Powder (1
in 1000) as directed under the Ultraviolet-visible Spec-
trophotometry: it exhibits a maximum between 281 nm

and 285 nm.
Assay Weigh accurately about 2.5 g of 10 % Dihydrocodeine Phosphate Powder and dissolve in water to make
exactly 100 mL. Pipet 2.0 mL of this solution, add 10.0
20 mL and use this solution as the test solution. Separately, weigh accurately about 50 mg of Dihydrocodeine
Phosphate RS, separately determined its loss on drying
o
(105 C , 4 hours) and dissolve in water to make exactly

100 mL. Pipet 10.0 mL of this solution, add exactly 10
mL of the internal standard solution and use this solution
and QS , of the peak area of dihydrocodeine to that of
the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of dihydrocodeine phosphate
(C18N23NO3H3PO4) = amount (mg) of Dihydrocodeine
Phosphate RS, calculated on the dried basis
QT
5
QS
Internal standard solutionA solution of Ethylefrine

Hydrochloride (3 in 10000).
about 40 C.
Mobile phase: Dissolve 1.0 g of sodium lauryl sulfate
in 500 mL of diluted phosphoric acid (1 in 1000) and adjust the pH to 3.0 with sodium hydroxide TS. To 240 mL
of this solution, add 70 mL of tetrahydrofuran.
time of dihydrocodeine is about 9 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, dihydrocodeine and the internal standard are eluted in this order with the resolution between

times with 20L of the standard solution under the above
the ratios of the peak area of dihydrocodeine to that of
1% Dihydrocodeine Phosphate
Powder
1% Hydrocodeine Phosphate Powder
1% Dihydrocodeine Phosphate Powder contains not less
than 0.90% and not more than 1.10% of dihydrocodeine
phosphate (C18N23NO3H3PO4: 399.38).
Phosphate RS, calculated on the dried basis
QT
QS
Internal standard solutionA solution of Ethylefrine

Hydrochloride (3 in 10000).
Perform as directed in Assay under 10% Dihydrocodeine Phosphate Powder.
Dihydroergotamine Mesilate
O
H
OH
CH3
H
N
O
N
H
100 g
Lactose Hydrate
To make 1000 g
solution of 1 % Dihydrocodeine Phosphate Powder (1 in
100) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 281 nm and
285 nm.
Assay Weigh accurately about 5 g of 1% Dihydrocodeine Phosphate Powder and dissolve in water to make exactly 100 mL. Pipet 10.0 mL of this solution, add 10.0
mL of the internal standard solution and use this solution
0.05 g of Dihydrocodeine Phosphate RS, separately determined its loss on drying (105 C, 4 hours) and dissolve in water to make exactly 100 mL. Pipet 10.0 mL of
dihydrocodeine to that of the internal standard, for the
Amount (mg) of dihydrocodeine phosphate

(C18N23NO3H3PO4) = amount (mg) of Dihydrocodeine
N
N
O
H
CH2
CH3SO 3H
CH3
H
HN
C33H37N5O5CH4O3S: 679.78
Dihydroergotamine Mesilate contains not less than
97.0% and not more than 101.0% of dihydroergotamine mesilate (C33H37N5O5CH4O3S), calculated on the
dried basis.
Description Dihydroergotamine Mesilate is a white to
yellowish white or grayish white to reddish white powder.
Dihydroergotamine Mesilate is freely soluble in glacial
acetic acid, sparingly soluble in methanol or in chloroform, slightly soluble in water or in ethanol and practically insoluble in acetic anhydride or in ether.
Dihydroergotamine Mesilate is gradually affected by
light.
Identification (1) Dissolve 1 mg of Dihydroergotamine Mesilate in 5 mL of a solution of tartaric acid (1 in
100). To 1 mL of this solution, add 2 mL of pdimethylaminobenzaldehyde-ferric chloride TS and
shake: a blue color is observed.
(2) Take 0.1 g of Dihydroergotamine Mesilate, add
0.4 g of sodium hydroxide, stir well and incinerate by
gradual ignition. After cooling, add 10 mL of water to the
residue, heat to boiling, cool and filter. To the filtrate,
add 0.5 mL of hydrochloric acid: the solution responds to
the Qualitative Tests for sulfate. Separately, to 0.1 g of
Dihydroergotamine Mesilate, add 5 mL of dilute hydrochloric acid, shake for 5 minutes, filter and to the filtrate, add 1 mL of barium chloride TS: the solution is
clear.
KP 9 305
Dihydroergotamine Mesilate and Dihydroergotamine
Mesilate RS in methanol (1 in 20000) as directed under
(4) Determine the infrared spectra of Dihydroergotamine Mesilate and Dihydroergotamine Mesilate RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
D : Between -16.7 and 22.7 [0.5 g, when dried, a mixture of dehydrated ethanol,
chloroform and strong ammonia water (10 : 10 : 1), 20
mL, 100 mm].
pH Dissolve 50 mg of Dihydroergotamine Mesilate in
and 5.4.
0.10 g of Dihydroergotamine Mesilate in 0.1 mL of a solution of methanesulfonic acid (7 in 100) and 50 mL of
water: the solution is clear and has no more color than
the following control solutions (1) or (2).
Control solution (1)Pipet 0.60 mL of ferric chloride stock CS and 0.150 mL of cobaltous chloride stock
CS, mix and add diluted hydrochloric acid (1 in 40) to
make exactly 100 mL.
Control solution (2)Pipet 0.60 mL of ferric chloride stock CS and 0.250 mL of cobaltous chloride stock
CS and 0.1 mL of cupric sulfate CS, mix and add diluted
hydrochloric acid (1 in 40) to make exactly 100 mL.
(2) Related substancesPerform this procedure
without exposure to daylight, using light-resistant vessels.
Dissolve 0.10 g of Dihydroergotamine Mesilate in 5 mL
of a mixture of chloroform and methanol (9 : 1) and use
this solution as the test solution. Pipet 1.0 mL of the test
solution, add a mixture of chloroform and methanol (9 :
1) to make exactly 200 mL and use this solution as the
standard solution (1). Pipet 10.0 mL of the standard solution (1), add a mixture of chloroform and methanol (9 :
standard solution (2). Perform the test with the test solution and the standard solutions (1) and (2) as directed
under the Thin-layer Chromatography. Spot 5 L each of
the test solution and the standard solutions (1) and (2) on
a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, ethylacetate, methanol and strong ammonia water (50 : 50 :
6 : 1) to a distance of about 15 cm and dry the plate with
cold wind within 1 minute. Develop the plate again immediately with a freshly prepared mixture of dichlorome-
thane, ethylacetate, methanol and strong ammonia water

(50 : 50 : 6 : 1) to a distance of about 15 cm and air-dry
the plate. Spray evenly p-dimethylaminobenzaldehyde
TS for spraying on the plate and dry the plate with warm
wind: the spots other than the principal spot from the test
solution (1) and the spots, which are more intense than
the spot from the standard solution (2), are not more than
two.
Loss on Drying Not more than 4.0% (0.5 g, at a pressure not exceeding 0.67 kPa, 100 C, 6 hours).
Assay Weigh accurately about 0.2 g of Dihydroergotamine Mesilate, dissolve in 170 mL of a mixture of acetic anhydride and glacial acetic acid (10 : 1) and titrate

= 13.596 mg of C33H37N5O5CH4O3S.

tight containers.
Dilazep Hydrochloride Hydrate

OCH 3
CH3O
O
O
CH3O
CH3O
OCH 2CH2CH2 N
CH2CH2CH2O C
OCH 3
2 HCl
H2O
OCH 3
C31H44N2O102HClH2O: 695.63
Dilazep Hydrochloride Hydrate contains not less than
98.0% and not more than 101.0% of dilazep hydrochloride (C31H44N2O102HCl), calculated on the dried basis.
Description Dilazep Hydrochloride Hydrate is a white,
Dilazep Hydrochloride Hydrate is freely soluble in glacial acetic acid or in chloroform, soluble in water,
slightly soluble in ethanol or in acetic anhydride and
Melting pointBetween 200 C and 204 C. Immerse the sample in a bath of 110 C and raise the temperature at the rate of about 3 C per minute from 140 C
to 150 C, about 10 C per minute from 160 C to 195
C and about 1 C per minute from 195 C.
Identification (1) Take 1 mL of a solution of Dilazep
Hydrochloride Hydrate (1 in 100), add 0.1 mL of a solution of hydroxylamine hydrochloride (1 in 10) and 0.1
mL of 8 mol/L potassium hydroxide TS and warm in a
water-bath of 70 C for 10 minutes. After cooling, add
0.5 mL of dilute hydrochloric acid and 0.1 mL of ferric
chloride TS: a purple color is observed.

(2) Take 5 mL of a solution of Dilazep Hydrochloride
Hydrate (3 in 500), add 0.3 mL of Reinecke salt TS: a
light red precipitate is produced.
Dilazep Hydrochloride Hydrate and Dilazep Hydrochloride Hydrate RS (1 in 50000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(4) Determine the infrared spectra of Dilazep Hydrochloride Hydrate and Dilazep Hydrochloride Hydrate
(5) A solution of Dilazep Hydrochloride Hydrate (1
in 50) responds to the Qualitative Tests for chloride.

= 33.881 mg of C31H44N2O102HCl
Diltiazem Hydrochloride
OCH3
pH Dissolve 1.0 g of Dilazep Hydrochloride Hydrate

in 100 mL of water: the pH of this solution is between
3.0 and 4.0.
g of Dilazep Hydrochloride Hydrate in 20 mL of water:
(2) SulfatePerform the test with 0.5 g of Dilazep
Hydrochloride Hydrate. Prepare the control solution with
0.048%).
(3) Heavy metalsProceed with 2.0 g of Dilazep
Hydrochloride Hydrate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL of
Dilazep Hydrochloride Hydrate according to Method 3
(5) Related substancesDissolve 0.40 g of Dilazep
Hydrochloride Hydrate in 10 mL of chloroform and use
chromatography. Develop the plate with a mixture of methanol, ethyl acetate, dichloromethane and hydrochloric
acid (500 : 200 : 100 : 1) to a distance of about 10 cm
and air-dry the plate. Spray evenly Dragendorffs TS for
spraying on the plate: the spots other than the principal
spot from the test solution are not more intense than that
Loss on Drying Between 2.0% and 3.0% (1 g, 105 C,
3 hours).
Assay Weigh accurately about 0.3 g of Dilazep Hydrochloride Hydrate dissolve in 40 mL of a mixture of
S
O
CH3
HCl
H
N
O
CH2CH2N(CH3)2
C22H26N2O4SHCl: 450.98
Diltiazem Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of diltiazem hydrochloride (C22H26N2O4SHCl).
Description Diltiazem Hydrochloride is a white crystal
Diltiazem Hydrochloride is very soluble in formic acid,
freely soluble in water, in methanol or in chloroform,
sparingly soluble in acetonitrile, slightly soluble in acetic
anhydride or in dehydrated ethanol and practically insoluble in ether.
Identification (1) Dissolve 50 mg of Diltiazem Hydrochloride in 1 mL of 1 mol/L of hydrochloric TS, add 2
mL of ammonium thiocyanate-cobalt nitrate TS and 5
mL of chloroform, shake well and allow to stand slowly:
a blue color is observed in the chloroform layer.
(2) Proceed as directed under the Oxygen Flask
Combustion Method with 30 mg of Diltiazem Hydrochloride, using 20 mL of water as the absorbing liquid and
prepare the test solution: the test solution responds to the
Qualitative Tests (1) for sulfate.
(3) Dissolve 10 mg each of Diltiazem Hydrochloride
and Diltiazem Hydrochloride RS in 0.01 mol/L hydrochloric acid TS to make 100 mL each. Pipet 2 mL each of
these solutions and add 0.01 mol/L hydrochloric acid TS
to make 20 mL each. Determine the absorption spectra of
these solutions as directed under the Ultraviolet-visible
(4) Determine the infrared spectra of Diltiazem Hydrochloride and Diltiazem Hydrochloride RS, previously
under the Infrared Spectrophotometry: both spectra exhi-
KP 9 307
bit similar intensities of absorption at the same wavenumbers.
(5) A solution of Diltiazem Hydrochloride (1 in 50)
pH Dissolve 1.0 g of Diltiazem Hydrochloride in 100
5.3.
1.0 g of Diltiazem Hydrochloride in 20 mL of water: the
(2) SulfatePerform the test with 1.0 g of Diltiazem
0.024%).
(3) Heavy metalsProceed with 2.0 g of Diltiazem
(4) ArsenicPlace 1.0 g of Ditiazem Hydrochloride
in a decomposition flask, add 5 mL of nitric acid and 2
mL of sulfuric acid, put a small funnel on the neck of the
flask and heat cautiously until white fumes are evolved.
After cooling, add 2 mL of nitric acid, heat and repeat
this procedure twice. Add several 2 mL volumes of
strong hydrogen peroxide water and heat until the solution changes colorless to pale yellow. After cooling, add
2 mL of saturated solution of ammonium oxalate and
heat again until white fumes are evolved. After cooling,
add water to make 5 mL, use this solution as the test solution and perform the test: the test solution has no more
color than the following control solution (not more than
2 ppm).
Control solutionProceed in the same manner as the

test solution without Diltiazem Hydrochloride, add 2.0
mL of standard arsenic solution and water to make 5 mL
and proceed in the same manner as the test solution.
(5) Related substancesDissolve 50 mg of Diltiazem Hydrochloride in 50 mL of diluted dehydrated ethanol (4 in 5) and use this solution as the test solution. Pipet 1.0 mL of the test solution, add diluted dehydrated
ethanol (4 in 5) to make exactly 200 mL and use this solution as the standard solution. Perform the test with 20
these solutions by automatic integration method: the total
peak area of peaks other than the peak of diltiazem obtained from the test solution is not more than 3/5 of the
peak area of diltiazem obtained from the standard solution.

Column: A stainless steel column, about 4 mm in inside diameter and about 15 cm to 30 cm in length,
chromatography (5 m to 10 m in particle diameter).
Column Temperature: A constant temperature of
about 50 C.
Mobile phase: Dissolve 8 g of sodium acetate and 1.5
g of d-camphorsulfonic acid in 500 mL of water and filter using a membrane filter (0.4 m in pore size). Add
250 mL each of acetonitrile and methanol to the filtrate
and adjust the solution to a pH of 6.6 by adding sodium
acetate. Make any necessary adjustment.
time of diltiazem is about 9 minutes.
System suitability
standard solution, add diluted dehydrated ethanol (4 in 5)
to make exactly 10 mL. Confirm that the peak area of
diltiazem obtained from 20 L of this solution is equivalent to 15 to 25% of that of diltiazem obtained from 20
System performance: Weigh 30 mg of Diltiazem
Hydrochloride, 20 mg of d-3-hydroxy-cis-2,3-dihydro-5[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5benzothiazepin-4-(5H)-one hydrochloride (i.e., deacetylated form) and 20 mg of phenylbenzoate, dissolve in
160 mL of dehydrated ethanol and add water to make
200 mL. Using 20 L of this solution, perform the test as
the above operating conditions: the deacetylated form,
diltiazem and phenylbenzoate are eluted in this order and
the resolution of the deacetylated form and diltiazem and
the resolution of diltiazem and phenyl benzoate are not
less than 2.5, respectively.
above operating conditions, the relative standard deviation of the peak area of diltiazem is not more than 2.0%.
the retention time of diltiazem after the solvent peak.
Loss on Drying
hours).
Not more than 0.5% (1 g, 105 C, 2

Assay Weigh accurately about 0.7 g of Diltiazem Hydrochloride, previously dried, dissolve in 2.0 mL of formic acid, add 60 mL of acetic anhydride and titrate with

= 45.10 mg of C22H26N2O4SHCl

tight containers.
Dimemorfan Phosphate
CH3
H
N
H3PO4
H3C
C18H25NH3PO4: 353.39
Dimemorfan Phosphate, when dried, contains not less
than 98.5% and not more than 101.0% of dimemorfan
phosphate (C18H25NH3PO4)
Description Dimemorfan Phosphate is a white to pale
yellowish white and crystal or crystalline powder.
Dimemorfan Phosphate is freely soluble in glacial acetic
acid, sparingly soluble in water or in methanol, slightly
soluble in ethanol and practically insoluble in ether.
solutions of Dimemorfan Phosphate and Dimemorfan
Phosphate RS (1 in 5000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Dimemorfan
Phosphate and Dimemorfan Phosphate RS, previously
under the Infrared Spectrophotometry: both spectra exhibits similar intensities of absorption at the same wavenumbers.
(3) Take 2 mL of a solution of Dimemorfan Phosphate (1 in 100) and add 2 to 3 drops of silver nitrate TS:
a yellow precipitate is formed and it dissolves on the addition of dilute nitric acid.
27 (after drying, 1 g, methanol, 100 mL, 100 mm).
pH Dissolve 1.0 g of Dimemorfan Phosphate in 100
5.0.
Purify (1) Heavy metalsProceed with 1.0 g of Dimemorfan Phosphate according to Method 1 and perform
(2) ArsenicProceed with 1.0 g of Dimemorfan
Phosphate according to Method 3 and perform the test.
Use 10 mL of a solution of magnecium nitrate in ethanol
(1 in 10) (not more than 2 ppm).
(3) Related substancesDissolve 0.10 g of Dimemorfan Phosphate in 10 mL of methanol and use this so-
lution as the test solution. Pipet 1.0mL of test solution,

test and standard solutions as directed under the Thinlayer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel for
mixture of methanol, chloroform and strong ammonia
water (150 : 150 : 1) to a distance of about 10 cm and airdry the plate. Spray evenly the plate with Dragendorffs
TS for spraying: the spots other than the principal spot
form the test solution are not more intense than that from
hours).
Assay Weigh accurately about 0.6 g of Dimemorfan
Phosphate, previously dried, dissolve in 100 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid

= 35.339 mg of C18H25NH3PO4
Dimenhydrinate
O
H
N
H3C
N
CHOCH2CH2N(CH3)2
Cl
O
CH3
C17H21NOC7H7ClN4O2: 469.96
Dimenhydrinate, when dried, contains not less than
53.0% and not more than 55.5% of diphenhydramine
(C17H21NO: 255.35) and not less than 44.0% and not
more than 47.0% of 8-chlorotheophylline (C7H7ClN4O2:
214.61).
Description Dimenhydrinate is a white, crystalline
powder, is odorless and has a bitter taste.
Dimenhydrinate is very soluble in chloroform, freely soluble in ethanol and slightly soluble in water or in ether.
Identification (1) Dissolve 0.5 g of Dimenhydrinate in
30 mL of dilute ethanol, add 30 mL of water and use this
solution as the test solution. Transfer 30 mL of the test
solution to a separatory funnel and add 2 mL of strong
ammonia water. Extract with two 10 mL volumes of ether, combine the ether extracts, wash the combined extracts with 5 mL of water and then extract the combined
KP 9 309
extracts with 15 mL of diluted hydrochloric acid (1 in
100). With this water layer, perform the following tests.
(i) Take 5 mL of this acid extract, add 5 drops of Reinecke salt TS: a light red precipitate is produced.
(ii) Take 10 mL of this acid extract, add 10 mL of picric
acid TS and allow to stand for 30 minutes. Collect the
precipitate by filtrating, recrystallize from dilute ethanol
and dry at 105 C for 30 minutes: the crystals melt between 128 C and 133 C.
(2) Take 30 mL of the test solution obtained in the
Identification (1), add 2 mL of dilute sulfuric acid and
cool for 30 minutes. Scratch the inside wall of the container frequently to facilitate crystallization: the white
crystals are produced. Filter and wash the white crystals
with a small amount of ice-cooled water. Dry the crystals
for 1 hour at 105 C: the crystals melt between 300 C
and 305 C with decomposition.
(3) Take 10 mg of the crystals obtained in the Identification (2), add 10 drops of hydrogen peroxide TS and 1
drop of hydrochloric acid and evaporate on a water-bath
to dryness: the residue shows a yellow-red color. When
the dish containing the residue is held over a vessel containing 2 to 3 drops of ammonia TS, the color changes to
red-purple, which is discharged on the addition of 2 to 3
drops of sodium hydroxide TS.
(4) Mix well 50 mg of crystals obtained in the Identification (2) with 0.5 g of sodium peroxide in a nickel
crucible and heat until the mass melts. Cool, dissolve the
melted mass in 20 mL of water and acidify with dilute
nitric acid: the solution responds to the Qualitative Tests
for chloride.
Melting Point
Purity (1) ChlorideTransfer 50 mL of the filtrate obtained in the Assay (2) to a Nessler tube, add 1 mL of nitric acid and allow to stand for 5 minutes: the turbidity of
the solution is not greater than that of the following control solution.
(2) Bromide and iodidePlace 0.10 g of Dimenhydrinate in a glass-stoppered test tube and add 50 mg of
sodium nitrite, 10 mL of chloroform and 10 mL of dilute
hydrochloric acid. Stopper, shake well and allow to
stand: the chloroform layer remains colorless.
Control solutionDilute 0.25 mL of 0.01 mol/L hydrochloric acid VS with 6 mL of dilute nitric acid and
with water to make 50 mL, add 1 mL of silver nitrate TS
and allow to stand for 5 minutes (not more than 0.044%).
P2O5, 24 hours).
Assay (1) DiphenhydramineWeigh accurately about
0.5 g of Dimenhydrinate, previously dried, transfer to a
separatory funnel and add 50.0 mL of water, 3 mL of
ammonia TS and 10 g of sodium chloride. Extract with
six 15 mL volumes of ether with shaking, combine the

ether extracts and wash the combined ether extracts with
three 50 mL volumes of water. To the ether extracts, add
25.0 mL of 0.05 mol/L sulfuric acid and 25 mL of water.
Shake thoroughly and evaporate the ether gently. Cool
and titrate the excess sulfuric acid with 0.1 mol/L sodium
hydroxide VS (indicator: 3 drops of methyl red TS). Perform a blank determination and make any necessary correction.
= 25.536 mg of C17H21NO
(2) 8-ChlorotheophyllineWeigh accurately about
0.8 g of Dimenhydrinate, previously dried, transfer to a
200 mL volumetric flask, add 50 mL of water, 3 mL of
ammonia TS and 6 mL of a solution of ammonium nitrate (1 in 10) and heat in a water-bath for 5 minutes.
Add 25.0 mL of 0.1 mol/L silver nitrate VS, heat in a water-bath for 15 minutes with occasional shaking, cool and
add water to make exactly 200 mL. Allow to stand overnight to settle the precipitate and filter through a dry filter paper. Discard the first 20 mL of filtrate, measure exactly 100 mL of the subsequent filtrate, acidify with nitric acid, add 3 mL of nitric acid and titrate the excess
silver nitrate with 0.1 mol/L ammonium thiocyanate VS
(indicator: 2 mL of ferric ammonium sulfate TS). Perform a blank determination and make any necessary correction.
= 21.461 mg of C7H7ClN4O2
Dimenhydrinate Injection
Dimenhydrinate Injection is a solution of Dimenhydrinate in a mixture of propylene glycol and water. Dimenhydrinate Injection contains not less than 95.0% and not
more than 105.0% of the labeled amount of dimenhydrinate (C17H21NOC7H7ClN4O2: 469.96).
Method of Preparation Prepare as directed under Injections, with Dimenhydrinate
Description Dimenhydrinate Injection is a clear, colorless liquid.
Identification (1) Pipet 5 mL of Dimenhydrinate Injection into a separatory funnel containing 35 mL of water.
Add 3 mL of ammonium hydroxide and 10 g of sodium
chloride and extract with three 50 mL volumes of ether.
Wash the combined ether extracts with 25 mL of water
until any color which is observed in the final washing by
the addition of 2 drops of phenolphthalein TS is dis-

charged by 1 drop of diluted hydrochloric acid (1 in 100).
Extract with 10 mL of water containing 0.3 mL of 3
mol/L hydrochloric acid TS: the aqueous extract obtained
meets the requirement under Identification (2) under Dimenhydrinate.
(2) Proceed with the precipitate of (1) as directed in
the Identification (3) and (4) under Dimenhydrinate.

It

8-Chlorotheophylline Content Transfer an exactly
measured volume of Dimenhydrinate Injection, equivalent to about 50 mg of Dimenhydrinate, add methanol to
make exactly 100 mL and mix. Pipet 5.0 mL of this solution, add methanol to make exactly 50 mL, mix and use
this solution as the test solution. Weigh a portion of Dimenhydrinate RS, previously dried in a desiccater (in vacuum, P2O5) for 24 hours, dissolve in methanol to make
a solution contain 0.5 mg of Dimenhydrinate per mL. Pipet 5.0 mL of this solution, add methanol to make exactly 50 mL, mix and use this solution as the standard solution. Perform the test with 25 L each of the test solution
and the standard solution as dircted under the Liquid
and determine the peak area, AT and AS , of these solutions, respectively. The retention time of 8chlorotheophylline is about 5 minutes.
Amount (mg/mL) of 8-chlorotheophylline (C7H7ClN4O2)

= 1000 C
V
AT
0 .45665
AS

V: Amount of Dimenhydrinate Injection (mL).
The amount of 8-chlorotheophylline is between 43.4%
and 47.9% of the Dimenhydrinate assayed.
Column: A stainless steel column, about 2 mm in inside diameter and about 12.5 cm in length, packed with
octadecylsilanized silica gel (30 m to 50 m) for liquid
chromatography and stainless steel column, about 4.6
mm in inside diameter and about 25 cm in length, packed
with octadecylsilianized silica gel (3 m to 10 m) for
liquid chromatography.
Mobile phase: Dissolve 0.81 g of d-camphor sulfuric
acid and 0.7 g of sodium acetic acid in 700 mL of water,
add 300 mL of methanol and mix.
System suitability
under the above operating conditions, the relative standard deviation of the peak areas is not more than 1.0%.

Assay Transfer an exactly measured volume of Dimenhydrinate Injection, equivalent to about 50 mg of
Dimenhydrinate, add methanol to make exactly 100 mL
and mix. Pipet 5.0 mL of this solution, add 5.0 mL of the
internal standard solution, mix and use this solution as
the test solution. Separately, weigh accurately about a
portion of dimenhydrinate RS, add methanol and dissolve to make the solution contain 0.5 mg per mL. Pipet
5.0 mL of this solution, add 5.0 mL of internal standard
solution, mix and use this solution as the standard solution. Perform the test with 25 L each of the test solution
and the standard solution, as directed under the Liquid
and calculate, QT and QS, the ratio of the peak area of
Dimenhydrinate to that of the internal standard for these
solutions, respectively.
Amount (mg/mL) of dimenhydrinate

Q
(C17H21NOC7H7ClN4O2) = 200 C T
V
QS

V: Amount of Dimenhydrinate (mL).
Internal stanadard solution2-hydroxybenzylalcohol in methanol (2.0 mg/mL).
octadecylsilianized silica gel for liquid chromatography
Mobile phase: Dissolve 0.8 g of ammonium bicarbonate in 800 mL of water, add 200 mL of methanol and
use this solution as mobile phase A. Dissolve 0.8 g of
ammonium bicarbonate in 150 mL of water, add 850 mL
of methanol and use this solution as mobile phase B.
During the first 7 minutes, flow the mobile phase A, then
8 minutes, flow the mobile phase B and then 7 minutes,
flow the mobile phase A.
System suitability
KP 9 311
above operating conditions, 8-chlorotheophylline and internal standard are eluted in this order with the resolution
of not less than 4.5.
standard deviation of the peak area is not less than 2.0%.
Internal standard solutionA solution of 2-hydroxy

benzylalcohol in methanol (2.0 mg/mL).
Dimercaprol
H
HS
Dimenhydrinate Tablets
Dimenhydrinate Tablets contain not less than 95.0% and
not more than 105.0% of the labeled amount of dimenhydrinate (C17H21NOC7H7ClN4O2: 469.96).
Method of Preparation Prepare as directed under Tablets, with Dimenhydrinate.
Identification (1) Weigh a portion of Dimenhydrinate
Tablets, previously powdered, equivalent to 0.5 g of Dimenhydrinate according to the labeled amount, with 25
mL of warm ethanol, mix with grinding and filter. Dilute
the filtrate with 40 mL of water and filter again. Use the
filtrate as the test solution. Transfer 30 mL of the test solution to a separatory funnel and proceed as directed in
the Identification (1) under Dimenhydrinate.
(2) With 30 mL of the test solution obtained in (1),
proceed as directed in the Identification (2), (3) and (4)
under Dimenhydrinate.
Dimenhydrinate Tablets. Weigh accurately a portion of
the powder, equivalent to about 50 mg of dimenhydrinate
(C17H21NOC7H7ClN4O2), transfer to a flask, add 80 mL
of methanol, shake well to mix, add methanol again to
make exactly 100 mL and filter. Pipet exactly 5 mL of
the filtrate, add 5.0 mL of the internal standard solution
weigh accurately about 25 mg of Dimenhydrinate RS,
add methanol to make exactly 50 mL. Pipet exactly 5 mL,
add 5.0 mL of the internal standard solution and use this
25 L each of the test solution and standard solution as
directed in the Assay under Dimenhydrinate Injection.
Amount (mg) of dimenhydrinate

(C17H21NOC7H7ClN4O2)
= amount (mg) of Dimenhydrinate RS
AT
2
AS
SH
OH
and enantiomer
C3H8OS2: 124.23
Dimercaprol contains not less than 98.5% and not more
than 101.5% of dimercaprol (C3H8OS2).
Description Dimercaprol is a colorless to pale to yellow liquid, and has a mercaptan-like, disagreeable odor.
Dimercaprol is soluble in peanut oil and sparingly soluble in water.
Dimercaprol is miscible with methanol or with dehydrated ethanol.
Dimercaprol shows no optical rotation.
Identification (1) Add 1 drop of Dimercaprol to a mixture of 1 drop of a solution of cobaltous chloride (1 in
200) and 5 mL of water: a yellow-brown color is observed.
(2) Determine the infrared spectra of Dimercaprol
and Dimercaprol RS as directed in the liquid film method
Refractive index
nD20 : Between 1.570 and 1.575.
Specific Gravity
20
: Between 1.238 and 1.248.
d 20

mL of Dimercaprol in 20 mL of peanut oil: the solution
(2) BromideTake 2.0 g of Dimercaprol, add 25 mL
of dilute potassium hydroxide-ethanol TS and heat in a
water-bath under a reflux condenser for 2 hours. Evaporate the ethanol with a current of warm air, add 20 mL of
water and cool. Add a mixture of 10 mL of strong hydrogen peroxide and 40 mL of water, boil gently under a reflux condenser for 10 minutes and filter rapidly after cooling. Wash the residue with two 10 mL volumes of water,
combine the washings with the filtrate, add 10 mL of dilute nitric acid and 5.0 mL of 0.1 mol/L silver nitrate VS
and titrate the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ferric ammonium sulfate TS). Perform a blank determination and

Not more than 1.0 mL of 0.1 mol/L silver nitrate VS is
consumed.
(3) Heavy metalsProceed with 1.0 g of Dimercaprol according to Method 2 and perform the test. Prepare
Assay Weigh accurately about 0.15 g of Dimercaprol
into a glass-stoppered flask, dissolve in 10 mL of methanol and titrate immediately with 0.05 mol/L iodine VS
until a pale yellow color is observed. Perform a blank determination and make any necessary correction.

= 6.211 mg of C3H8OS2
Packaging and Storage Preserve in hermetic containers. Store in a cold place.
Dimorpholamine
O
O
O
N
CH3CH2CH2CH2
CH2CH2
CH2CH2CH2CH3
C20H38N4O4: 398.54

Store at 5 C or less.
Dimercaprol Injection
Dimercaprol Injection is an oily solution for injection.
Dimercaprol Injection contains not less than 95.0 percent
and not more than 105.0 percent of the labeled amount of
dimercaprol (C3H8OS2: 124.23).
Method of Preparation Prepare as directed under Injections, with Dimercaprol. Benzyl Benzoate or Benzyl
Alcohol may be added to increase the solubility.
Description Dimercaprol Injection is a clear, colorless
to light yellow liquid and has an unpleasant odor.
Identification Measure a volume of Dimercaprol Injection, equivalent to 30 mg of Dimercaprol according to
the labeled amount, and proceed as directed in the Identification (1) under Dimercaprol.

= 6.211 mg of C3H8OS2
It

Assay Transfer an exactly measured volume of Dimercaprol Injection, equivalent to about 0.1 g of dimercaprol
(C3H8OS2), into a flask, rinse the pipet several times with
a mixture of methanol and chloroform (3 : 1) and add the
rinsings to the flask. Add a mixture of methanol and
chloroform (3 : 1) to make 50 mL, and titrate with 0.05
mol/L iodine VS until a yellow color persists. Perform a
blank determination, and make any necessary correction.
Dimorpholamine, when dried, contains not less than

98.0% and not more than 101.0% of dimorpholamine
(C20H38N4O4).
Description Dimorpholamine is a white to pale yellow,
crystalline powder, mass or syrupy liquid.
Dimorpholamine is very soluble in dehydrated ethanol or
in acetic anhydride and soluble in water.
When dissolve 1.0 g of Dimorpholamine in 10 mL of
water, pH of this solution is between 6.0 and 7.0.
Dimorpholamine is hygroscopic.
solutions of Dimorpholamine and Dimorpholamine RS
(2) Determine the infrared spectra of Dimorpholamine and Dimorpholamine RS, previously dried, as directed in the potassium bromide disk method under the
1.0 g of Dimorpholamine in 50 mL of water: the solution
(2) ChlorideTake 20 mL of the solution obtained
in (1), add 6 mL of dilute nitric acid and water to make
(3) SulfateTake 10 mL of the solution obtained in
(1), add 1 mL of dilute hydrochloric acid and water to
test solution. Prepare the control solution with 0.40 mL
of 0.005 mol/L sulfuric acid VS (not more than 0.096%).
(4) Heavy metalsProceed with 2.0 g of Dimorpholamine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(5) Related substancesDissolve 2.0 g of Dimorpholamine in 10 mL of dehydrated ethanol and use this
KP 9 313
solution as the test solution. Pipet exactly 1 mL of this
solution, add dehydrated ethanol to make exactly 100 mL
fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dehydrated methanol
and water (4:1) to a distance of about 10 cm and air-dry
the plate. Allow the plate to stand in iodine vapor for 10
minutes: the spot other than the principal spot from the
standard solution.
solution of acetaldehyde (1 in 20), 0.1 mL of sodium

pentacyanonitrosyl ferrate (III) TS and 0.5 mL of sodium
carbonate TS : a blue color develops.

P2O5, 8 hours).


Assay Weigh accurately about 0.6 g of Dimorpholamine, previously dried, dissolve in 50 mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid VS
Titrimetry). Perform a blank determination, and make

= 39.85 mg of C20H38N4O4
tight containers.
Dimorpholamine Injection
Dimorpholamine Injection is an aqueous solution for Injection. Dimorpholamine Injection contains not less than
of dimorpholamine (C20H38N4O4: 398.54).
Method of Preparation Prepare as directed under Injections, with Dimorpholamine.
Description Dimorpholamine Injection is a clear, colorless liquid.
Identification (1) Take a volume of Dimorpholamine
Injection, equivalent to 0.1 g of Dimorpholamine according to the labeled amount and add 3 drops of Dragendorffs TS: an orange color is observed.
(2) Take a volume of Dimorpholamine Injection,
equivalent to 50 mg of Dimorpholamine according to the
labeled amount, add 1 mL of dilute hydrochloric acid and
evaporate on a water-bath to dryness. Dissolve this residue in 2 mL of hydrohloric acid, boil for 10 minutes under a reflux condenser, and evaporate to dryness on a water bath. Dissolve the residue with 1 mL of water, neutralize with sodium hydroxide TS, and add 0.2 mL of a

Bacterial Endotoxins Less than 5.0 EU per mg of Dimorpholamine Injection. Perform the test with the sample diluted to 0.15 w/v% with water for bacterial endotoxins test.
It
Assay Take exactly a volume of Dimorpholamine Injection, equivalent to about 30 mg of dimorpholamine

(C20H38N4O4) and add water to make exactly 200 mL.
Pipet 1.0 mL of this solution, shake with exactly 4 mL of
the internal standard solution for 5 minutes and use this
about 0.15 g of Dimorpholamine RS, previously dried in
a desiccator (in vacuum, P2O5) for 8 hours and dissolve
in water to make exactly 1000 mL. Pipet 1.0 mL of this
solution, shake with exactly 4 mL of the internal standard
peak area of dimorpholamine to that of the internal standard solution for these solutions, respectively.
Amount (mg/mL) of dimorpholamine (C20H38N4O4)

= amount (mg) of Dimorpholamine RS
QT 1
QS 5
Internal standard solutionA solution of butyl parahydroxybenzoate in acetonitrile (1 in 25000).

octadecylsilianized silica gel for liquid chromatogrphy (5
about 40 C.
1).
time of dimorpholamine is about 4 minutes.
System suitability

above operating conditions, the relative standard deviation of the ratio of the peak area of dimorpholamine to
Dinoprost
H
HO
CO2H
CH3
HO
H
HO
C20H34O5: 354.48
Dinoprost contains not less than 98.5% and not more
than 101.0% of dinoprost (C20H34O5), calculated on the
anhydrous basis.
Description Dinoprost is white, waxy masses or
powder or clear, colorless to pale yellow and viscous liquid, and is odorless.
Dinoprost is very soluble in dimethylformamide, freely
soluble in methanol, in dehydrated ethanol or in ether
and very slightly soluble in water.
Identification (1) Weigh 5 mg of Dinoprost, add 2 mL
of sulfuric acid and dissolve by shaking for 5 minutes: a
dark red color is observed. To this solution, add 30 mL of
sulfuric acid: an orange color is observed with green fluorescence.
(2) Dissolve 1 mg each of Dinoprost and Dinoprost
RS in 50 mL of diluted sulfuric acid (7 in 10) and warm
in a water-bath for 50 C for 40 minutes. After cooling,
determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
(3) Warm separately Dinoprost and Dinoprost RS at
40 C to make a liquid and determine the infrared spectra
of the liquids as directed in the liquid film method under
31 (0.2 g, dehydrated ethanol, 10 mL, 100 nm).
g of Dinoprost in 5 mL of dehydrated ethanol: the solution is clear and colorless to pale yellow.
(2) Related substancesDissolve 10 mg of Dinoprost in 2 mL of methanol, add water to make 10 mL and

test solution, add diluted methanol (1 in 5) to make exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution
Determine each peak area of these solutions by the automatic integration method: the total area of the peaks
other than the peak of Dinoprost from the test solution is
not larger than the peak area of Dinoprost from the standard solution.
Column: A stainless steel column, about 5 mm in inside diameter and about 15 cm in length, packed with octadecylsilianized silica gel for liquid chromatography (5
about 25 C.
potassium phosphate TS and acetonitrile (5 : 2).
time of Dinoprost is about 20 minutes.
System suitability
System performance: Dissolve 10 mg each of isopropyl parahydroxybenzoate and propyl parahydroxybenzoate in 2 mL of methanol and add water to make
10 mL. Take 1 mL of this solution, add diluted methanol
(1 in 5) to make 30 mL. When the procedure is run with
10 L of this solution as directed under the above operating conditions, isopropyl parahydroxybenzoate and
propyl parahydroxybenzoate are eluted in this order with
a resolution between their peaks being not less than 2.5.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Dinoprost from the standard
solution composes 5.0% to 15.0% of the full scale.
long as the retention time of Dinoprost after the solvent
peak.
direct titration).
Assay Weigh accurately about 50 mg of Dinoprost,
dissolve in 30 mL of dimethylformamide and titrate with
0.02 mol/L tetramethylammonium hydroxide VS under a
stream of nitrogen (potentiometric titration, Endpoint

hydroxide VS = 7.090 mg of C20H34O5
tight containers. Store in a place not exceeding 5 C.
KP 9 315
F: Relative response factor
Ai : the peak area for each related substance obtained
AS : the peak area for dinoprostone obtained from the
standard solution
Dinoprostone
COOH
CH3
HO
H
OH
Prostaglandin E2
C20H32O5 : 352.47
Dinoprostone contains not less than 97.0% and not more

than 103.0% of dinoprostone (C20H32O5), calculated on
Description Dinoprostone is a white or light gray,
Dinoprostone and Dinoprostone RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) When proceed as directed in the Assay, the retention time of the principal peak from the test solution corresponds to that from the standard solution.
D : Between -82 and 90 (0.1 g, ethanol 20 mL, 100 mm).
Purity Related substancesWeigh 25.0 mg of Dinoprostone, add the mobile phase to make exactly 10 mL
weigh 25.0 mg of Dinoprostone RS, add the mobile
standard solution (1). To 0.5 mL of the standard solution
(1), add the mobile phase to make 50 mL and use this solution as the standard solution (2). Perform the test with
(2) as directed under the Liquid Chromatography according to the following operating conditions. Determine the
area of each peak in these solutions by the automatic integration method and calculate the content of each related substance according to the following equation: the
content of each related substance corresponds to the values given in the following table.
Content (%) of each related substance

= C 1 Ai
W
AS
C: Concentration (g/mL) of Dinoprostone RS in the

standard solution (2)
W: Weight (mg) of Dinoprostone to prepared the test
solution
Table. Relative response factor and the limit

Relative
Related substance
retention
F
time
Limit
15-oxo-dinoprostone
0.79
15-epi-dinosprostone
0.85
1.1
8-isodinoprostone
0.90
1.0
5,6-trans-dinoprostone
1.15
1.0
*
Not more than
2.0%
1.80
Not more than

2.0%
1.90
1.43
Not more than

2.0%
1.0
Not more than

0.1% of total
other related
substances
present
(5Z,13E,15S)-15hydroxy-9-oxoprosta-5,
10, 13 -triene-1-oic acid
(5Z,13E,15S)-15hydroxy-9-oxoprosta-5,
8(12), 13-triene-1-oic
acid
Any other related substance
* The sum of these three related substances is not more

than 1.0%.
about 30 C.
Mobile phase: A mixture of methanol and 0.2% acetic acid (58:42)
Flow rate: 1 mL/min
System suitability
operating conditions, the number of theoretical plates is
not less than 6000. The resolution between dinoprostone
peak and any other adjacent peak in the chromatogram
obtained from the injection of the test solution is not less
than 1.0.
times with 20 L each of the standard solution (1) under
the above operating conditions, the relative standard deviation of the areas of the principal peak is not more than
2.0%.
direct titration).

Assay Weigh accurately about 25 mg of Dinoprostone,
add the mobile phase to make exactly 10 mL and use this
solution as the test solution. Separately, weigh 25 mg of
Dinoprostone RS, add the mobile phase to make exactly
10 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the operating conditions directed
in the Related substances under the Purity and determine
the area of dinoprostone peak in the test solution, AT ,
and in the standard solution, AS .

Amount (mg) of dinoprostone (C20H32O5)
= amount (mg) of Dinoprostone RS
AT
AS
System suitability
with 20 L of the standard solution according to the operating condition directed in related substances under
Purity, the resolution between dinoprostone peak and any
other adjacent peak is not less than 1.0.
times with 20 L each of the standard solution according
to the operating condition directed in related substances
under Purity, the relative standard deviation of the areas
of the principal peak is not more than 2.0%.

Diosmin and Diosmin RS as directed in the potassium
(2) When proceed as directed in the Assay, the retention time and the size of the principal peak from the test
solution corresponds to that from the standard solution.
Purity (1) Heavy metalsProceed with 2.0 g of Diosmin according to Method 2, and perform the test. Prepare the control solution with 4.0 mL of standard lead solution (not more than 20 ppm).
(2) IodinePrepare the test solution with 1.0 g of
Diosmin as directed under the Oxygen Flask Combustion
Method, using 50 mL of 0.02 w/v% hydrazine solution
as an adsorbing liquid. Separately, weigh accurately 1.66
g of potassium iodide, dissolve in water to make exactly
100 mL. Pipet 2 mL of this solution, add water to make
exactly 100 mL and use this solution as the control solution. Weigh 20 g of potassium nitrate and dissolve in 0.1
mol/L nitric acid to make 100 mL. Transfer 30 mL of the
solution to a beaker, immerse an iodide ion selective
electrode, stir for 10 minutes until the potential of the solution is stable ( nT1 ). Add 1 mL of the test solution and
measure the potential ( nT 2 ). Separately, weigh 20 g of

potassium nitrate, dissolve in 0.1 mol/L nitric acid to
make 100 mL. Transfer 30 mL of the solution to a beaker,
immerse an iodide ion selective electrode, stir for 10 minutes until the potential of the solution is stable ( n R1 ).
Add 80 L of the control solution and measure the potential ( nR2 ). The absolute value, nT 2 nT 1 , is less
than the absolute value, nR 2 nR1 .
Diosmin
OH
OCH3
OH
O
O
CH3
OH
OH
OH
OH
OH
OH
C28H32O15:
608.55
Diosmin contains not less than 90.0% and not more than
102.0% of diosmin (C28H32O15), calculated on the anhydrous basis.
Description Diosmin is a grayish-yellow or light yellow powder.
Diosmin is soluble in dimethylsulfoxide and practically
insoluble in water or in ethanol.
Diosmin is soluble in dilute sodium hydroxide TS.
Diosmin is hygroscopic.

Diosmin, dissolve in dimethylsulfoxide to make exactly
25 mL and use this solution as the test solution. Separately, weigh accurately 25 mg of Diosmin RS, dissolve in
dimethylsulfoxide to make exactly 25 mL. Pipet 5 mL of
this solution, add dimethylsulfoxide to make 100 mL and
according to the following operating conditions and determine the area of the peaks in these solutions by the automatic integration method. Multiply the peak areas by
0.38 and 0.61 for the related substances I and VI, respectively, for the calculation of the content of the related
substances: the area of the related substance I peak obtained from the test solution is not more than 0.2 times
the area of the principal peak obtained from the standard
solution (1%), the area of the related substance II peak
from the test solution is not more than the area of the
principal peak from the standard solution (5%) and the
individual area of the related substances III, V and VI
peaks from the test solution is not more than 0.6 times
KP 9 317
the area of the principal peak from the standard solution.
In addition, the area of the peak of any other related substance from the test solution is not more than 0.2 times
the area of the principal peak from the standard solution
(1%), the area of the related substance I peak and total
area of other related substances from the test solution are
0.2 times the area of the principal peak from the standard
solution, and total area of the related substance peaks is
not more than twice the area of the principal peak from
the standard solution (10%). Disregard any peak having
the area not more than 0.02 times (0.1%) the area of the
principal peak from the standard solution.
Mobile phase: A mixture of acetonitrile, glacial acetic acid, methanol and water (2:6:28:66).
Relative retention time: The reference retention time
for diosmin peak is about 4.6 min. The retention times
for the related substances I, II, III, IV, V and VI are
about 0.5, 0.6, 0.8, 2.2, 2.6 and 4.5 minutes, respectively.
System suitability
System performance: Weigh 25 mg of Diosmin
and dissolve in dimethylsulfoxide to make 25 mL. When
related substance II and the related substance III is not
less than 2.5.
direct titration).
Diphenhydramine
CHOCH2CH2N(CH3)2
C17H21NO: 255.36
Diphenhydramine contains not less than 96.0% and not
more than 101.0% of diphenhydramine (C17H21NO).
Description Diphenhydramine is a clear, pale yellow
to yellow liquid, has a characteristic odor and has a burning taste at first, followed by slight sensation of numbness on the tongue.
Diphenhydramine is miscible with glacial acetic acid,
with acetic anhydride, with ethanol, or with ether.
Diphenhydramine is very slightly soluble in water.
Boiling pointAbout 162 C (in vacuum, 0.67 k Pa).
Refractive index nD20 : About 1.55.
Diphenhydramine is gradually affected by light.
Identification (1) Take 50 mg of Diphenhydramine
and add 2 mL of sulfuric acid: an orange-red precipitate
is produced immediately and its color changes to redbrown on standing. Add carefully 2 mL of water to this
solution: the intensity of the color changes, but the color
tone does not change.
(2) Dissolve 0.1 g of Diphenhydramine in 10 mL of
dilute ethanol, add an excess of a saturated solution of
picric acid in dilute ethanol with stirring and cool in ice.
Collect the produced crystals, recrystallize from dilute
ethanol and dry at 105 C for 30 minutes: the crystals
melt between 128 C and 133 C.

Specific Gravity
Assay Weigh accurately 25 mg each of Diosmin and
Diosmin RS, dissolve in dimethylsulfoxide to make 25
mL each and use these solutions as the test solution and
to the operating conditions in the Related substances under the Purity and determine the area of the principal
peak of the test solution, AT , and the standard solution,
AS .
Amount (mg) of diosmin (C28H32O15)
= amount (mg) of Diosmin RS
AT
AS
20
: Between 1.103 and 1.020.
d 20
Purity (1) -DimethylaminoethanolDissolve 1.0 g

of Diphenhydramine in 20 mL of ether and extract with
two 10 mL volumes of water with thorough shaking.
Combine the water extracts and add 2 drops of phenolphthalein TS and 1.0 mL of 0.05 mol/L sulfuric acid VS: no
(2) BenzohydrolTransfer 1.0 g of Diphenhydramine to a separatory funnel, dissolve in 20 mL of ether
and extract with two 25 mL volumes of diluted hydrochloric acid (1 in 15) with thorough shaking. Separate the
ether layer, evaporate slowly in a water-bath and dry in a
desiccator (in vacuum, silica gel) for 2 hours: the weight
of the residue is not more than 20 mg.
(3) Heavy metalsProceed with 1.0 g of Diphenhydramine according to Method 2 and perform the test.

Assay Weigh accurately about 0.5 g of Diphenhydramine, dissolve in 50 mL of a mixture of acetic anhydride
and glacial acetic acid (7 : 3) and titrate with 0.1 mol/L

= 25.535 mg of C17H21NO
tight and almost well-filled containers.
Diphenhydramine Hydrochloride
CHOCH2CH2N(CH3)2
HCl
C17H21NOHCl: 291.82
Diphenhydramine Hydrochloride, when dried, contains
not less than 98.0% and not more than 101.0% of diphenhydramine hydrochloride (C17H21NOHCl).
Description
Diphenhydramine Hydrochloride is a
white crystal or crystalline powder, is odorless and has a
bitter taste, followed by sensation of numbness on the
tongue.
Diphenhydramine Hydrochloride is very soluble in methanol or in glacial acetic acid, freely soluble in water or
in ethanol, sparingly soluble in acetic anhydride and
Diphenhydramine Hydrochloride is gradually affected by
light.
solutions of Diphenhydramine Hydrochloride and Diphenhydramine Hydrochloride RS in methanol (1 in
(2) Determine the infrared spectra of Diphenhydramine Hydrochloride and Diphenhydramine Hydrochloride RS, both previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Diphenhydramine Hydrochloride (1 in
pH Dissolve 1.0 g of Diphenhydramine Hydrochloride

and 5.0.
1.0 g of Diphenhydramine Hydrochloride in 10 mL of
(2) Heavy metalsProceed with 1.0 g of Diphenhydramine Hydrochloride according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of
(3) Related substancesDissolve 0.20 g of Diphenhydramine Hydrochloride in 10 mL of methanol and use
solution, add methanol to make exactly 200 mL and use
with 20 L each of the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography.
Develop the plate with a mixture of hexane, ethyl acetate,
methanol and strong ammonia water (10 : 4 : 2 : 1) to a
evenly iodine TS on the plate: the spots other than the
principal spot from the test solution and the spot on the
original point are not more intense than that from the
standard solution.
hours).
Assay Weigh accurately about 0.4 g of Diphenhydramine Hydrochloride, previously dried, dissolve in 50 mL
(7 : 3). Titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 29.182 mg of C17H21NOHCl.

tight containers.
Capsules
Diphenhydramine Hydrochloride Capsules contain not
amount
of
diphenhydramine
hydrochloride
(C17H21NOHCl: 291.82).
KP 9 319

Capsules, with Diphenhydramine.
Identification (1) Weigh a portion of Diphenhydramine Hydrochloride Capsules, equivalent to about 50 mg
of Diphenhydramine Hydrochloride and perform the test
as directed in the Identification (2) under Diphenhydramine Hydrochloride Injection.
(2) The retention of the principal peak in the chromatogram corresponds to that of the standard preparation, as
obtained in the Assay.
Dissolution Test Take 1 capsule of Diphenhydramine
Hydrochloride Capsules and perform the test using 500
mL of water as dissolution solution, at 100 revolutions
per minute according to Method 1 under the Dissolution
Test. After 30 minutes start from the test, take the dissolved solution and filter. Discard the first 10 mL of the
filtrate and use the subsequent filtrate as the test solution.
Separately, weigh accurately a portion of Diphenhydrao
mine Hydrochloride RS, previously dried at 105 C for

3 hours and dissolve in water at the same concentration
as the test solution and use this solution as the standard
solution. Perform the test with 50 L of the test solution
and the standard solution, as directed according to Assay
under Diphenhydramine Hydrochloride Injection.
The dissolution rate of Diphenhydramine Hydrochloride
Capsules in 30 minutes is not less than 80%.
Assay Weigh accurately not less than 20 Diphenhydramine Hydrochloride Capsules. Transfer an accurately
weighed portion of the powder, equivalent to about 50
mg of Diphenhydramine Hydrochloride, dissolve in water to make exactly 100 mL and filter. Perform the test as
directed according to Assay under Diphenhydramine
Hydrochloride Injection.
Amount (mg) of diphenhydramine hydrochloride

(C17H21NOHCl) = amount (mg) of Diphenhydramine
Hydrochloride RS
AT
AS
Injection
Diphenhydramine Hydrochloride Injection is a sterile solution of Diphenhydramine Hydrochloride in water for
Injection. Diphenhydramine Hydrochloride Injection
at the labeled amount of diphenhydramine hydrochloride
(C17H21NOHCl: 291.82).
Method of Preparation Prepare as directed under Injections, with Diphenhydramine.
Description Diphenhydramine Hydrochloride Injection is a clear, colorless liquid.
Identification (1) The retention of the principal peak
in the chromatogram corresponds to that of the standard
preparation.
(2) Take a volume of Diphenhydramine Hydrochloride Injection, equivalent to about 50 mg of Diphenhydramine Hydrochloride, add 0.03 mol/L sulfuric acid TS
to make 25 mL, filter if necessary and use this solution
as the test solution. Separately, to 50 mg of Diphenhydramine Hydrochloride RS, add 0.01 mol/L hydrochloric
acid TS to make 25 mL and use this solution as the standard solution. To each of the test solution and the standard solution, add 2 mL of 1 mol/L sodium hydroxide TS
and 4 mL of carbon disulfide and shake for 2 minutes.
Filter by centrifugation, if necessary and proceed as directed in the solution method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Bacterial Endotoxins Less than 3.4 EU per mg of Diphenhydramine Hydrochloride.
It

Assay Transfer an accurately pipeted portion of Diphenhydramine Hydrochloride Injection, equivalent to
about 50 mg of Diphenhydramine Hydrochloride, add
water to make exactly 100 mL and use this solution as
the test solution. Weigh accurately about 50 mg of Diphenhydramine Hydrochloride, previously dried at 105
C for 3 hours, dissolve in water to make 100 mL and use
with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and determine AT
and AS , the peak area of diphenhydramine hydrochloride.

Amount (mg) of diphenhydramine hydrochloride
(C17H21NOHCl) = amount (mg) of Diphenhydramine
Hydrochloride RS
AT
AS
Temperature: A room temperature.
Mobile Phase: Adjust pH to 6.5 by adding glacial acetic
acid to a mixture of acetonitrile, water and triethylamine
(50 : 50 : 0.5). Adjust, if necessary
System suitability
System performance: Dissolve 5 mg of benzophenone in 5 mL of acetonitrile and add water to make 500
mL. To 1 mL of this solution, add 5 mg of Diphenhydramine Hydrochloride and water to make 10 mL. When
the procedure is run with 10 L of this solution as directed under the above operating conditions, benzophenone and diphenhydramine are eluted in this order with
the resolution between their peaks being greater than 2.0.
under the above operating conditions, the relative standard deviation of the peak areas is not more than 2.0%.
Diphenhydramine Tannate
and allow to stand for 30 minutes. Collect the precipitate

by filtration, recrystallize from dilute ethanol and dry at
105 C for 30 minutes: the crystals melt between 128 C
and 133 C.
(3) Take 1 mL of the test solution obtained in (1) and
1 drop of ferric chloride TS: a dark blue-purple color
deve1ops.
Purity Heavy metalsProceed with 1.0 g of Diphenhydramine Tannate according to Method 2 and perform
hours).
Assay Transfer about 1.7 g of Diphenhydramine Tannate, accurately weighed, to a separatory funnel, dissolve
in 20 mL of water and 3.0 mL of dilute hydrochloric acid
with thorough shaking, add 20 mL of a solution of sodium hydroxide (1 in 10) and exactly 25 mL of isooctane,
shake vigorously for 5 minutes, dissolve 2 g of sodium
chloride with shaking and allow to stand. Pipet 20.0 mL
of the isooctane layer, add 80.0 mL of glacial acetic acid

= 25.535 mg of Cl7H21NO
tight containers.
Diphenhydramine Tannate is a compound of Diphenhydramine and Tannic Acid and contains not less than
25.0% and not more than 35.0% of diphenhydramine
(Cl7H21NO: 255.35).
Description Diphenhydramine Tannate is a grayish
white to light brown powder, is odorless or has a slight,
characteristic odor and is tasteless.
Diphenhydramine Tannate is slightly soluble in ethanol
and practically insoluble in water or in ether.
Identification (1) Weigh 1 g of Diphenhydramine
Tannate, add 15 mL of water and 0.3 mL of dilute hydrochloric acid, shake thoroughly for 1 minute, filter and
use this filtrate as the test solution. Transfer 10 mL of the
test solution to a separatory funnel, extract with two 20
mL volumes of chloroform, combine the chloroform extracts and evaporate on a water-bath to dryness. Take 5
mL of a solution of the residue (1 in 100), add 5 drops of
Reinecke salt TS: a light red precipitate is produced.
(2) Take 10 mL of a solution of the residue obtained
in (1) (1 in 100), add 10 mL of picric acid TS drop-wise
Residue on Ignition
Dipyridamole
N
CH2CH2OH
N
N
HOCH 2CH2
HOCH 2CH2
CH2CH2OH
N
N
N
C24H40N8O4: 504.63
Dipyridamole, when dried, contains not less than 98.5%
and not more than 101.0% of dipyridamole (C24H40N8O4).
Description Dipyridamole is a yellow crystal or crystalline powder, is odorless and has a slightly bitter taste.
KP 9 321
Dipyridamole is freely soluble in chloroform, sparingly
soluble in methanol or in dehydrated ethanol and practically insoluble in water or in ether.
Identification (1) Dissolve 5 mg of Dipyridamole in 2
mL of sulfuric acid, add 2 drops of nitric acid and shake:
a deep purple color is observed.
Dipyridamole and Dipyridamole RS in a mixture of methanol and hydrochloric acid (99 : 1) (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
(3) Determine the infrared spectra of Dipyridamole
and Dipyridamole RS, previously dried, as directed in
Melting Point

g of Dipyridamole in 10 mL of chloroform: the solution
is clear and shows a yellow color.
(2) Heavy metalsProceed with 2.0 g of Dipyridamole according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(3) ArsenicProceed with 1.0 g of Dipyridamole
than 2 ppm).
(4) Related substancesDissolve 50 mg of Dipyridamole in 50 mL of the mobile phase and use this solution as the test solution. Pipet 0.50 mL of the test solution, add the mobile phase to make exactly 100 mL and
method: the total area of the peak other than the peak of
Dipyridamole from the test solution is not larger than the
peak area of Dipyridamole from the standard solution.
about 40 C.
Mobile phase: Dissolve 0.2 g of monobasic potassium phosphate in 200 mL of water and add 800 mL of
methanol.
time of Dipyridamole is about 4 minutes.
System suitability
System performance: Dissolve 7 mg of Dipyridamole and 3 mg of p-terphenyl in 50 mL of methanol.

When the procedure is run with 20 L of this solution as
directed under the above operating conditions, Dipyridamole and p-terphenyl are eluted in this order with the
resolution between their peaks being not less than 5.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Dipyridamole obtained
from 20 L of the standard solution is between 2 mm and
6 mm.
as the retention time of Dipyridamole.
hours).
Assay Weigh accurately about 0.6 g of Dipyridamole,
previously dried, dissolve in 70 mL of methanol and titrate with 0.1 mol/L perchloric acid VS (potentiometric

= 50.46 mg of C24H40N8O4

Dirithromycin
O
NH
H3CO
H3C
CH3
OH
HO
O
H3C
CH3
N(CH3)2
HO
H3C
O
CH3
CH3
O
O
CH3
O
H3C
OCH3
CH3
OH
C42H78N2O14: 835.07
Dirithromycin contains not less than 950 g (potency)

and not more than 1020 g (potency) per mg of dirithromycin and epidirithromycin (C42H78N2O14), calculated
on the anhydrous basis. Epidirithromycin is not more
than 2 %.
Description Dirithromycin is whtie to grayish white
powder.
Dirithromycin is freely soluble in chloroform, soluble in
methanol, slightly soluble in propanol or in acetonitrile,

and very slightly soluble in water or in cyclohexane.
Identification (1) Determine the infrared spectra of Dirithromycin and Dirithromycin RS, as directed in the potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) Heavy metalsProceed with 0.1 g of Dirithromycin according to Method 2 and perform the test.
(2) Related compoundsWeigh accurately 0.1 g of
Dirithromycin, dissolve in the mixture of acetonitrle and
methanol (70:30), make to exactly 10 mL and use this
10 mg of Dirithromycin RS, dissolve in the mixture of
acetonitrle and methanol (70:30), make to exactly 50 mL,
the test with 10 L of each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the Assay operating conditions, 9(S)-erythromycilamine and dirithromicin are eluted in
this order. Prepare the test solution and the standard solution before use. Determine the amount of 9-(S)erythromycilamine according to the following equation,
the amount is not more than 1.5 %. Other related substances are not more than 1.0 %, and total amount of related substances is not more than 5.0 %.
Content ratio of 9-(S)-erythromycilamine or other related

substances (%) =
AT1 W S 1
100
AS W A 5
AT1 : the peak area response corresponding to 9-(S)erythromycilamine or other related substances of the test
solution
AS : the peak area of dirithromycin of the standard
solution
WS : the potency (mg) of Dirithromycin RS
WA : the amount (mg) of Dirithromycin
Content ratio of total related substances (%)

=
AT2 W S 1
100
AS W A 5
AT2 : the sum of the peak area of all peaks except dirithromycin and solvent, of the test solution
AS : the peak area of dirithromycin of the standard solu-
tion
WS : the potency (mg) of Dirithromycin RS
WA : the amount (mg) of Dirithromycin
direct titration).
Assay (1) Dirithromycin Weigh accurately an amount
of Dirithromycin and Dirithromycin RS, equivalent to
about 20 mg (potency), dissolve each in the mixture of
acetonitrle and methanol (70:30) and make exactly 10
standard solution. Perform the test with exactly 10 L
the Assay (2) conditions, and determine the peak areas,
AT and AS , of dirithromycin.
(2) Epidirithromycin Weigh accurately an amount
of Dirithromycin, equivalent to about 0.1 g (potency),
dissolve each in the mixture of acetonitrile and methanol
(70:30) and make exactly 10 mL, and use this solution as
the test solution. Separately, weigh accurately an amount
of Dirithromycin RS, equivalent to about 10 mg (potency), dissolve each in the mixture of acetonitrile and methanol (70:30) and make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and determine the
peak areas, AT and AS, of epidirithromycin. Prepare the
test solution and the standard solution before use.
Amount [g (potency)] of dirithromycin or epidirithromycin

= Amount [g (potency)] of dirithromycin RS
AT
AS
Amount [g (potency)] of Dirithromycin

= Amount [g (potency)] of dirithromycin + Amount [g
(potency)] of epidirithromycin
Column temperature: A room temperature or 40 C
Mobile phase: A mixture of acetonitirile, 0.05 mol/L
phosphate buffer solution (pH 7.5) and ethanol
(44:37:19)
Flow rate: 2.0 mL per minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, dirithromycin and epidirithromycin
KP 9 323
are eluted in this order.
Disopyramide
O
(CH 3)2CH
NCH 2CH 2
NH 2
(CH 3)2CH
N
and enantiomer
C21H29N3O: 339.47
Disopyramide contains not less than 98.5% and not more
than 101.0% of disopyramide (C21H29N3O), calculated
on the dried basis.
Description Disopyramide is a white crystal or crystalline powder.
Disopyramide is very soluble in methanol or in ethanol,
freely soluble in acetic anhydride, in glacial acetic acid
or in ether and slightly soluble in water.
Identification (1) Take 1 mL of a solution of Disopyramide in ethanol (1 in 20), add 10 mL of picric acid TS
and warm: a yellow precipitate is produced. Filter this
precipitate, wash with water and dry at 105 C for 1
hour: the residue melts between 172 C and 176 C.
Disopyramide and Disopyramide RS in 0.05 mol/L sulfuric acid-methanol TS (1 in 25000) as directed under the
(3) Determine the infrared spectra of Disopyramide,
same wavenumbers.
(3) Related substancesDissolve 0.40 g of Disopyramide in 10 mL of the methanol and use this solution as
the test solution. Pipet 1.0 mL of the test solution, add
with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of n-butanol, water
and strong ammonia water (45 : 4 : 1) to a distance of
about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots are not
80 C, 2 hours).
Assay Weigh accurately about 0.25 g of Disopyramide,
dissolve in 30 mL of glacial acetic acid and titrate with

= 16.97 mg of C21H29N3O
Distigmine Bromide
CH3
CH3
N
CH3
O
C
O
2 Br-
CH3
N(CH2)6N
C22H32Br2N4O4: 576.32
%
Absorbance E11cm
(10 mg, 0.05 mol/L sulfuric acid-methanol TS, 500 mL).
Distigmine Bromide contains not less than 98.5% and

not more than 101.0% of distigmine bromide
(C22H32Br2N4O4), calculated on the anhydrous basis.
Purity (1) Heavy metalsDissolve 1.0 g of Disopyramide in 10 mL of ethanol and add 2 mL of dilute acetic
acid and water to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add
10 mL of ethanol, 2 mL of dilute acetic acid and water to
(2) ArsenicProceed with 1.0 g of Disopyramide
than 2 ppm).
Description Distigmine Bromide is a white, crystalline

powder and odorless.
Distigmine Bromide is very soluble in water, freely soluble in methanol, in glacial acetic acid or in ethanol,
slightly soluble in acetic anhydride and practically insoluble in ether.
When dissolve 1.0 g of Distigmine Bromide in 100 mL
of water, pH of this solution is between 5.0 and 5.5.
Bromide is slightly hygroscopic.
Distigmine Bromide is gradually colored by light.

solutions of Distigmine Bromide and Distigmine Bromide RS (1 in 25000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Distigmine
Bromide and Distigmine Bromide RS as directed in the
(3) Take 5 mL of a solution of Distigmine Bromide
(1 in 10), add 2 mL of dilute nitric acid: the solution responds to the Qualitative Tests (1) for bromide.
0.25 g of Distigmine Bromide in 5 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.40 g of Distigmine Bromide. Prepare the control solution with 0.40 mL
of 0.005 mol/L sulfuric acid VS (not more than 0.048%)
(3) Heavy metalsProceed with 2.0 g of Distigmine
Bromide according to Method 2 and perform the test.
(4) Related substancesDissolve 0.040 g of Distigmine Bromide in 10 mL of methanol and use this solution as the test solution. Pipet 1.0 mL of this solution,
test solution and the standard solution on a plate of cellulose with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of n-butanol,
water, dehydrated ethanol and glacial acetic acid (8 : 3 :
solution are not more intense than the spot from the standard solution. Spray evenly Dragendorgff's TS for spraying on the plate: the spots other than the principal spot
from the test solution are not more intense than that from
direct titration).
Assay Weigh accurately about 0.4 g of Distigmine
Bromide, dissolve in 60 mL of a mixture of acetic anhydride and glacial acetic acid (8 : 1) and titrate with 0.1
mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry with platinum electrode). Perform a blank determination and make any necessary correction.

= 28.816 mg of C22H32Br2N4O4
tight containers.
Distigmine Bromide Tablets

Distigmine Bromide Tablets contain not less than 95.0%
and not more than 105.0% of the labeled amount of distigmine bromide (C22H32Br2N4O4: 576.32).
Method of Preparation Prepare as directed under Tablets, with Distigmine Bromide.
Identification (1) Take a portion of powdered Distigmine Bromide Tablets, equivalent to 0.1 g of Distigmine
Bromide according to the labeled amount, add 25 mL of
water, shake, filter and use the filtrate as the test solution.
To 5 mL of the test solution, add 3 mL of picric acid TS
and proceed as directed in the Identification (2) under
Distigmine Bromide.
(2) Determine the absorption spectrum of the solution
obtained in the Assay, as directed under the Ultravioletvisible Spectrophotometry: it exhibits a maximum between 268 nm and 272 nm and a minimum between 239
nm and 243 nm.
(3) With 5 mL of the test solution obtained in (1),
proceed as directed in the Identification under Distigmine Bromide.
Assay Weigh accurately not less than 20 tablets of Distigmine Bromide Tablets and powder. Weigh accurately a
portion of the powder, equivalent to about 15 mg of distigmine bromide (C22H32Br2N4O4), add 30 mL of 0.1
mol/L hydrochloric acid TS, shake for 1 hour, add 0.1
mol/L hydrochloric acid TS to make exactly 50 mL and
filter. Discard the first 20 mL of the filtrate, pipet 10.0
mL of the subsequent filtrate, add 0.1 mol/L hydrochloric
acid TS to make exactly 100 mL and use this solution as
the test solution. Separately, weigh accurately about 0.03
g of Distigmine Bromide RS (previously determined the
water) and dissolve in 0.1 mol/ L hydrochloric acid TS to
make exactly 100 mL. Pipet 10.0 mL of this solution,
add 0.1 mol/L hydrochloric acid TS to make exactly 100
mL and use this solution as the standard solution. Determine the absorbances of the test solution and the standard solution, AT2 and AS2, at 270 nm and, ATl and AS1, at
241 nm as directed under the Ultraviolet-visible Spectrophotometry, respectively.
Amount (mg) of distigmine bromide (C22H32Br2N4O4) =

amount (mg) of Distigmine Bromide RS,
KP 9 325
AT2- AT1
1
calculated on the anhydrous basis A - A 2
S2
S1
Disulfiram
S
(CH3CH2)2N
S
S
N(CH2CH3)2
C10H20N2S4: 296.54
Disulfiram, when dried, contains not less than 99.0% and
not more than 101.0% of disulfiram (C10H20N2S4).
Description Disulfiram is a white to yellowish crystal
Disulfiram is freely soluble in acetone or in toluene,
slightly soluble in methanol or in ethanol and practically
insoluble in water.
solutions of Disulfiram and Disulfiram RS in methanol
(2) Determine the infrared spectra of Disulfiram and
Disulfiram RS as directed in the potassium bromide disk
same wavenumbers.
Purity (1) Heavy metalsProceed with 2.0 g of Disulfiram according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(2) ArsenicWeigh 1.0 g of Disulfiram according to
method 4 and perform the test (not more than 2 ppm).
(3) Diethyldithiocarbamic acidDissolve 0.10 g of
Disulfiram in 10 mL of toluene and shake with 10 mL of
diluted sodium carboxylate TS (1 in 20). Take the water
layer separately, wash that with 10 mL of toluene, shake
with 5 drops of a solution of cupuric sulfate (1 in 250)
and 2 mL of toluene and allow to stand: a pale yellow
color is not observed in the toluene layer.
(4) Related substancesDissolve 50 mg of Disulfiram in 40 mL of methanol, add water to make 50mL, and
use this solution as the test solution . Pipet 1mL of the
mL, and use this solution as the standard solution. Perform the test with exactly 10 L each of the test solution
Determine each peak area of both solutions by the automatic integration method: the total area of the peaks oth-
er than the peak of disulfiram from the test solution is not

larger than the peak area of disulfiram from the standard
solution.
about 25 C.
Mobile phase: A mixture of methanol and water (7:3).
time of disulfiram is about 8 minutes.
Selection of column: Dissolve 50 mg of Disulfiram
and 50mg of benzophenone in 40 mL of methanol, and
add water to make 50 mL. To 1 mL of this solution add
the mobile phase to make 200 mL. Proceed with 10 L
of this solution under the above operating conditions, and
calculate the resolution. Use a column giving elution of
benzophenone and disulfiram in this order with the resolution between these peaks being not less than 4.
so that the peak height of disulfiram obtained from 10 L
of the standard solution is 15 - 30 mm.
Time span of measurement: About 3.5 times of the
retention time of disulfiram.
Loss on Drying Not more than 0.20% (2 g, silica gel,
24 hours).
Assay Weigh accurately about 0.2 g of Disulfiram,
previously dried, in an iodine bottle, dissolve in 20 mL of
acetone, add 1.5 mL of water and 1.0 g of potassium
iodide and dissolve by shaking thoroughly. To this solution, add 3.0 mL of hydrochloric acid, stopper the bottle
tightly, shake and allow to stand in a dark place for 3 minutes. Add 70 mL of water and titrate with 0.1 mol/L sodium thiosulfate VS (potentiometric titration, Endpoint
Each mL of 0.1 mol/L sodium thiosulfate VS

= 14.83 mg of C10H20N2S4
Dobutamine Hydrochloride
OH
H
CH3
N
H
HCl
OH

hours).
HO
and enantiomer
C18H23NO3.HCl: 337.84
Dobutamine Hydrochloride, when dried, contains not
less than 98.0 % and not more than 101.0% of dobutaime
hydrochloride (C18H23NO3.HCl).
Description Dobutamine Hydrochloride is a white to
very pale orange crystalline powder or grain.
It is freely soluble in methanol, sparingly soluble in water or in dehydrated ethanol, and practically insoluble in
ether.
A solution of Dobutamine Hydrochloride (1 in 100)
spectra of Dobutamine Hydrochloride and Dobutamine
Hydrochloride RS, previously dried, as directed in the
(2) A solution of Dobutamine Hydrochloride (1 in
50) responds to the Qualitative Tests (2) for chloride.
Melting Point

chloroform, methanol and formic acid (78:22:5) to a distance of about 12 cm, and air-dry the plate. Allow the
plate to stand for 5 minutes in iodine vapor: the spots
pH Dissolve 1.0 g of Dobutamine Hydrochloride in

and 5.5.
g of Dobutamine Hydrochloride in 30 mL of water: the
(2) Heavy metalsDissolve 1.0 g of Dobutamine
Hydrochloride in 40 mL of water by warming, cool, and
add 2 mL of dilute acetic acid and water to make 50 mL.
standard lead solution add water to make 50 mL (not
more than 20 ppm).
(3) Related substancesDissolve 0.10 g of Dobutamine Hydrochloride in 10 mL of methanol, and use this
solution as the test solution. Pipet 1 mL of the test solution, add methanol to make exactly 200 mL, and use this

Assay Weigh accurately about 0.1 g each of Dobutamine Hydrochloride and Dobutamine Hydrochloride RS,
previously dried, dissolve in exactly 10 mL each of the
internal standard solution, add diluted methanol (1 in 2)
to make 50 mL each, and use these solutions as the test
solution and standard solution respectively. Perform the
according to the following conditions, and calculate the
ratios, QT and QS , of the peak area of dobutamine to
that of the internal standard for the test solution and
Amount (mg) of dobutamine hydrochloride

(C18H23NO3.HCl)
= amount (mg) of Dobutamine Hydrochloride RS
QT
QS
Internal standard solutionA solution of salicylamide in diluted methanol (1 in 2) (1 in 125).
about 25 C.
Mobile phase: A mixture of tartaric acid buffer solution, pH 3.0 and methanol (7:3).
time of dobutamine is about 7 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, dobutamine and internal standard are
above operating conditions, the relative standard deviation of the ratios of the peak area of dobutamine to that
KP 9 327
Domperidone
N
N
O
N
N
H
O
N
H
Cl
C22H24Cl N5O2: 425.91

Domperidone, when dried, contains not less than 99.0%
and not than 101.0% of domperidone (C22H24Cl N5O2).
Description Domperidone is a white powder.
Domperidone is soluble in dimethylformamide, slightly
soluble in ethanol and in methanol, and practically insoluble in water.
Identification (1) Dissolve 5 mg of Domperidone in 3
mL of methanol, add 0.1 mL each of 10w/v% cobaltous
nitrate solution and 10w/v% calcium chloride solution,
mix and add 0.1 mL of 2 mol/L sodim hydroxide TS: a
purple-blue color develops and precipitate is formed.
(2) Determine the infrared spectrum of Domperidone
and Domperidone RS, previously dried, as directed in the
(3) Dissolve 20 mg of Domperidone in 10 mL of methanol, and use this as the test solution. Separately, dissolve 20 mg of Domperidone RS in 10 mL of methanol,
and use this as the standard solution (1). Dissolve 20 mg
of Domperidone RS and 20 mg of Droperidole RS in 10
mL of methanol, and use this as the standard solution (2).
test solution, the standard solutions (1) and (2) on a plate
of octadecylsilyl silica gel for thin-layer chromatography.
Develop the plate with a mixture of ammonium acetate
solution, dioxan and methanol (20 : 40 : 40) to a distance
of about 15 cm, and air-dry the plate. Expose the plate to
iodine vapor until the spots appear and examine in daylight: the principal spot in the chromatogram obtained
with the test solution is similar in size and Rf value to
the principal spot from the standard solution (1). The test
is not valid unless the chromatogram from the standard
solution (2) shows clearly separated spots.
Melting Point

g in 20 mL of dimethylformamide: the solution is color-
less and clear.

(2) Heavy metals Proceed with 1.0 g of Domperidone according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(3) Related substancesPrepare the solutions for the
test immediately before use. Dissolve 0.1 g of Domperidone in 10 mL of dimethylformamide, and use this solution as the test solution. Pipet 1 mL of the test solution,
and add dimethylformamide to make exactly 100 mL.
Pipet 5 mL of this solution, add dimethylformamide to
make exactly 20 mL, and use this solution as the standard solution (1). Perform the test with 10 L each of
dimethylformamide (as a blank solution), the test solution, and the standard solution (1) as directed under the
Liquid Chromatography according to the following conditions. Determine each peak area from each solution by
the automatic integration method: the area of peaks other
than the peak of domperidone from the test solution is
not larger than the peak area of domperidone from the
standard solution (1) (0.25 %), and the total area of all
peak other than the peak of domperidone from the test
solution is not larger than twice the peak area of domperidone from the standard solution (1) (0.5 %). Disregard
any peak in the chromatogram obtained with the blank
solution and any peak with an area less than 0.2 times the
area of the peak of domperidone from the standard solution (1).
Column: A stainless steel column, 4.6 mm in inside
diameter and about 100 cm in length, packed with basedeactivated octadecylsilanized silica gel for liquid chromatography (3 m in particle diameter).
Column temperature: A Room temperature
Mobile phase: At a flow rate of 1.5 mL per minute a
mixture of ammonium acetate (5 g/L) and methanol (70 :
30), changing by linear gradient to methanol over 10 min,
followed by elution with methanol for 2 min.
Flow rate: 1.5 mL/minute. Equilibrate the column for
at least 30 min with methanol and then equilibrate at the
initial mobile phase composition (a mixture of ammonium acetate (5 g/L) and methanol (70 : 30) for at least 5
minutes.
System suitability
Selection of column: Dissolve 10 mg of Domperidone RS and 15 mg of Droperidol RS in 100 mL of dimethylformamide and use this solution as the standard
solution (2). Proceed with 10 L of the standard solution
(2) under the above operating conditions. Use a column
from which the retention time for domperidone and droperidol is 6.5 minutes and 7 minutes, respectively, with
the resolution between these peaks being not less than
2.0. If necessary, adjust the concentration of methanol in
the mobile phase or adjust the time program for the linear gradient.
Detection sensitivity: Adjust the detection sensitiv-

ity so that the peak height of domperidone from 10 L of
the standard solution (1) is not less than 50.0 percent of
the full scale of the recording chart.
Loss on Drying Not more than 0.5% (1 g, 100 ~ 105
C, constant weight).
Assay Weigh accurately about 0.3 g of Domperidone,
previously dried, dissolve in 50 mL of a mixture of glacial acetic acid and methyl ethyl ketone (1 : 7), and titrate with 0.1 mol/L perchloric acid (indictor: 0.2 mL of
-naphtholbenzein TS) until the color changes from
orange-yellow to green.
Each mL of 0.1 mol/L perchloric acid

= 42.59 mg of C22H24Cl N5O2

Domperidone Maleate
N
N
CO2H
O
N
H
N
O
CO2H
N
H
Cl
C22H24Cl N5O2C4H4O4: 541.98

Domperidone Maleate contains not less than 99.0% and
not more than 101.0% of domperidone maleate
(C22H24Cl N5O2C4H4O4), calculated on the anhydrous
basis.
Description Domperidone Maleate occurs as a white
powder.
Domperidone Maleate is sparingly soluble in dimethylformamide, slightly soluble in methanol, and very
slightly soluble in water or in ethanol.
It shows polymorphism.
Identification (1) Triturate 0.1 g of Domperidone Maleate with a mixture of 1 mL of strong sodium hydroxide
solution and 3 mL of water. Shake with three quantities,
each of 5 mL, of ether. Add 0.1 mL of the aqueous layer
to the solution of 10 mg of resorcinol in 3 mL of sulfuric
acid. Heat on a water-bath for 15 min. No color develops.
To the remainder of aqueous layer add 2 mL of bromine
solution. Heat on a water-bath for 15 min and then heat
to boiling. Cool. Add 0.1 mL of the solution to a solution
of 10 mg of resorcinol in 3 mL of sulfuric acid. Heat on a
water-bath for 15 minutes. A violet color develops.
(2) Determine the infrared spectra of Domperidone
Maleate and Domperidone Maleate RS as directed in the

potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensity of
absorption at the same wavenumbers. If the spectra obtained show differences, dissolve each substance in minimum volume of isopropanol, evaporate to dryness on a
water-bath and record new spectra using the residues.
(3) Dissolve 20 mg of Domperidone Maleate in 10
mL of methanol, and use this solution as the test solution.
Separately, dissolve 20 mg of Domperidone Maleate RS
in 10 mL of methanol, and use this as the standard solution (1). Dissolve 20 mg of Domperidone Maleate RS
and 20 mg of Droperidole RS in 10 mL of methanol, and
use this as the standard solution (2). Perform the test with
these solutions as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution, the standard solutions (1) and (2) on a plate of silica gel for thinlayer chromatography. Develop the plate with a mixture
of acetate ammonium acetate solution, dioxan, and methanol (20 : 40 : 40) to a distance of about 15 cm and airdry the plate. Expose the plate with iodine vapor until
spots appear and examine in day-light: the principal spot
in the chromatogram obtained with the test solution corresponds in the size and the Rf value to that with the
standard solution (1) and the two spots in the chromatogram obtained with the standard solution (2) are clearly
separated with each other.
g in 20 mL of dimethylformamide. The solution is clear
and not darker than the mixture of 5 mL of the mixed solution of Cobaltous Chloride Colorimetric Stock Solution,
Ferric Chloride Colorimetric Stock Solution, and 1 w/v%
hydrochloric acid (6 : 24 : 70) and 95 mL of 1 w/v% hydrochloric acid.
(2) Heavy metals Proceed with 1.0 g of Domperidone Maleate according to Method 4, and perform the
(3) Related substances Prepare the solution immediately before use. Dissolve 0.1 g of Domperidone Maleate in 10 mL of dimethylformamide, and use this solution as the test solution. Pipet 1 mL of the test solution,
and add dimethylformamide to make exactly 100 mL.
Pipet 5 mL of this solution, add dimethylformamide to
make exactly 20 mL, and use this solution as the standard solution (1). Perform the test with 10 L each of
dimethylformamide (as a blank solution), the test solution, and the standard solution (1) as directed under the
Liquid Chromatography according to the following conditions. Determine each peak area from each solution by
the automatic integration method: the area of peaks other
than the peak of domperidone maleate from the test solution is not larger than the peak area of domperidone maleate from the standard solution (1) (0.25 %), and the total area of all peak other than the peak of domperidone
maleate from the test solution is not larger than twice the
peak area of domperidone maleate from the standard so-
KP 9 329
lution (1) (0.5 %). Disregard any peak in the chromatogram obtained with the blank solution and any peak with
an area less than 0.2 times the area of the peak of domperidone maleate from the standard solution (1).
diameter and about 100 cm in length, packed with basedeactivated octadecylsilyl silica gel for liquid chromatography (3 m in particle diameter).
Mobile phase: At a flow rate of 1.5 mL per minute a
mixture of ammonium acetate (5 in 1000) and methanol
(70 : 30), changing by linear gradient to methanol over
10 min, followed by elution with methanol for 2 min.
Flow rate: 1.5 mL/minute. Equilibrate the column for
at least 30 min with methanol and then equilibrate at the
initial mobile phase composition (a mixture of ammonium acetate (5 in 1000) and methanol (70 : 30)) for at
least 5 minutes.
System suitability
System performance: Dissolve 10 mg of Domperidone Maleate RS and 15 mg of Droperidol RS in 100 mL
of dimethylformamide and use this solution as the standard solution (2). When the procedure is run with 10 L
of this solution, as directed under the above operating
conditions, Domperidone maleate and Droperidol are
Detection sensitivity: Adjust the detection sensitivity so that the peak height of domperidone maleate from
10 L of the standard solution (1) is not less than 50.0
percent of the full scale.
Loss on Drying Not more than 0.5% (1 g, 105 C, constant mass).
Assay Weigh accurately 0.4 g of Domperidone Maleate,
previously dried, dissolve in 50 mL of a mixture of glacial acetic acid. Titrate with 0.1 mol/L perchloric acid
until the color changes from orange-yellow to green (indicator: 0.2 mL of naphtholbenzein solution TS).

= 54.20 mg of C26H28Cl N5O6
Packaging and Storage Preserve in well-closed containers, protected from light.
Dopamine Hydrochloride
HO
HO
CH2CH2NH2
HCl
C8H11NO2HCl: 189.64
Dopamine Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of dopamine hydrochloride (C8H11NO2HCl).
Description Dopamine Hydrochloride occurs as a
Dopamine Hydrochloride is freely soluble in water or in
formic acid, sparingly soluble in ethanol.
solutions of Dopamine Hydrochloride and Dopamine
Hydrochloride RS in 0.1 mol/L hydrochloric acid TS (1
(2) Determine the infrared spectra of Dopamine Hydrochloride and Dopamine Hydrochloride RS as directed
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers
(3) A solution of Dopamine Hydrochloride (1 in 50)
pH Dissolve 1.0 g of Dopamine Hydrochloride in
50mL of water: the pH of this solution is between 4.0
and 5.5.
g of Dopamine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.8 g of Dopamine
0.021%).
(3) Heavy metalsProceed with 1.0 g of Dopamine
(4) ArsenicProceed with 1.0 g of Dopamine Hydrochloride according to Method 1 and perform the test
(5) Related substancesDissolve 0.10 g of Dopamine Hydrochloride in 10 mL of water and use this solution as the test solution. Pipet 1.0 mL of the test solution,
add water to make exactly 250 mL and use this solution
as the standard solution. Perform the test with the test solution and the standard solutions as directed under the

solution and the standard solution on a plate of cellulose
Develop the plate with a mixture of n-butanol, water and
glacial acetic acid (16 : 8 : 1) to a distance of about 10
cm and air-dry the plate. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate and heat at 90 C
for 10 minutes: the spots other than the principal spot
form the test solution are not more intense than that from
hours).
Assay Weigh accurately about 0.2 g of Dopamine Hydrochloride, previously dried, dissolve in 5 mL of formic
acid, add 15.0 mL of 0.1 mol/L perchloric acid VS and
heat on a water-bath for 15 minutes. After cooling, add
50 mL of glacial acetic acid and titrate the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.


tight containers.
Doxapram Hydrochloride
Hydrate
CH2CH3
N
HCl
O
H2O
CH2CH2
H
and enantiomer
C24H30N2O2HClH2O: 432.98
Doxapram Hydrochloride Hydrate contains not less than
98.0% and not more than 101.0% of doxapram hydrochloride (C24H30N2O2HCl: 414.97), calculated on the anhydrous basis.
Description Doxapram Hydrochloride occurs as a
Doxapram Hydrochloride is freely soluble in methanol or
in glacial acetic acid, sparingly soluble in water, in ethanol, or in acetic anhydride and practically insoluble in
ether.
solutions of Doxapram Hydrochloride Hydrate and Doxapram Hydrochloride Hydrate RS (1 in 2500) as directed
same wavelengths.
(2) Determine the infrared spectrum of Doxapram
Hydrochloride Hydrate and Doxapram Hydrochloride
Hydrate RS as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Doxapram Hydrochloride Hydrate
(1 in 50) responds to the Qualitative Tests for chloride.
Melting Point
pH Dissolve 1.0 g of Doxapram Hydrochloride Hydrate in 50 mL of water: the pH of this solution is between 3.5 and 5.0.
g of Doxapram Hydrochloride Hydrate in 50 mL of water: the solution is clear and colorless
(2) SulfatePerform the test with 1.0 g of Doxapram Hydrochloride Hydrate. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.024%).
(3) Heavy metalsProceed with 2.0 g of Doxapram
Hydrochloride Hydrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
(4) ArsenicProceed with 1.0 g of Doxapram Hydrochloride Hydrate according to Method 3 and perform
(5) Related substancesDissolve 0.5 g of Doxapram
Hydrochloride Hydrate in 10 mL of methanol and use
solution and add methanol to make exactly 100 mL. Pipet 5.0 mL of this solution, add methanol to make exactly 50 mL and use this solution as the standard solution.
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
formic acid, ethyl formate and methanol (8 : 3 : 3 : 2) to
a distance of about 10 cm and air-dry the plate. Allow the
plate to stand in iodine vapor: the spots other than the
KP 9 331
Assay Weigh accurately about 0.8 g of Doxapram Hydrochloride Hydrate, dissolve in 50 mL of a mixture of

Doxorubicin Hydrochloride
OH
OH
OH
OH
H3C
HCl
H3C
O
NH2
OH
C27H29NO11HCl: 579.98
bicin Hydrochloride is used in a sterile preparation.

doxorubicin hydrochloride, when Doxorubicin Hydrochloride is used in a sterile preparation.
Histamine It meets the requirement, when Doxorubicin Hydrochloride is used in a sterile preparation. Weigh
appropriate amount of Doxorubicin Hydrochloride, dissolve in water, make the solution so that each mL contains 2.0 mg, use the solution as the test solution, and use
0.5 mL of the solution for the test.
direct titration).
Assay Weigh accurately an amount of Doxorubicin
Hydrochloride and Doxorubicin Hydrochloride RS,
equivalent to about 10 mg (potency), dissolve each in
water to make exactly 25 mL. Pipet 5 mL each of these
solutions, add water to make exactly 100 mL, and use
these solutions as the test solution and the standard solution, respectively. Determine the absorbances at 495 nm,
AT and AS , of the test solution and the standard solution as directed under Ultraviolet-visible Spectrophotometry.
Doxorubicin Hydrochloride is the hydrochloride of a derivative of daunorubicin.

Doxorubicin Hydrochloride contains not less than 900
g (potency) of per mg of doxorubicin hydrochloride
(C27H29NO11HCl), calculated on the anhydrous basis.
Amount [g (potency)] of Doxorubicin Hydrochloride

(C27H29NO11HCl)
= Amount [g (potency)] of Doxorubicin Hydrochloride
Description Doxorubicin Hydrochloride is a red-orage

crystalline powder.
Doxorubicin Hydrochloride is sparingly soluble in water,
slightly soluble in methanol, very slightly soluble in
ethanol, and practically insoluble in ether.
Identification (1) Dissolve 1 ~ 2 mg of Doxorubicin

Hydrochloride in 5 mL of 1 mol/L sodium hydroxide: a
blue-purple color develops.
of Doxorubicin Hydrochloride in methanol (1 in 100000)
as directed under Ultraviolet-visible Spectrophotometry,
it exhibits maxima between 231 nm and 235 nm, and between 250 nm and 254 nm, and between 286 nm and 290
nm, and between 477 nm and 481 nm, and between 493
nm and 497 nm, and between 527 nm and 531 nm.
of Doxorubicin Hydrochloride in 10 mL of water is between 4.0 and 5.5.
%
E11cm
Absorbance
(495 nm): 200 ~ 230 (10 mg calculated on the anhydrous basis, methanol, 500 mL).
Sterility Test It meets the requirement, when Doxoru-
RS
AT
AS
Doxycycline Hyclate Hydrate

OH
OH
OH
O
NH2
C2H6O H2O
HCl
OH
H
H
CH3
H
OH
N(CH3)2
(C22H24N2O8HCl)2C2H6OH2O: 1025.88
Doxycycline Hyclate Hydrate contains not less than 800
g (potency) and not more than 920g (potency) per mg
of doxycycline (C22H24N2O8: 444.44), calculated on the
anhydrous basis and corrected by the amount of ethanol.
Description Doxycycline Hyclate Hydrate is yellow to
dark yellow crystal or crystalline powder.
Doxycycline Hyclate Hydrate is freely soluble in water
and in methanol, slightly soluble in ethanol, and practically insoluble in ether.

Identification (1) To 1 mg of Doxycycline Hyclate
Hydrate add one drop of sulfuric acid: a yellow color develops.
(2) Dissolve 10 mg of Doxycycline Hyclate Hydrate
in 10 mL of water, and add silver nitrate TS: a white turbidity is produced.
(3) To 2 mL of the solution of Doxycycline Hyclate
Hydrate in water (1 in 20) add two drops of chromic acid
sulfuric acid TS, mix well, and heat: a smell of acetaldehyde develops.
(4) Determine the infrared spectra of Doxycycline
Hyclate Hydrate and Doxycycline Hyclate Hydrate RS,
the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Ethanol Weigh accurately about 0.1 g of Doxycycline Hyclate Hydrate, dissolve in the internal standard solution to make exactly 10 mL, and use this solution as
the test solution. Separately, weigh accurately about 0.4 g
of dehydrated ethanol, add the internal standard solution
to make exactly 100 mL. Pipet 1 mL of this solution, add
the internal standard solution to make exactly 10 mL,
the test with 1 L each of the test solution and the standard solution as directed under Gas Chromatography according to the following conditions, and determine the
ratios, QT and QS , of the peak area of ethanol to that of
the internal standard:the amount of ethanol is not less
than 4.3 % and not more than 6.0 %.
Amount [%] of ethanol

= (Amount [mg] of ethanol / Amount [mg] of
Doxycycline Hyclate Hydrate)
QT
QS
Internal standard solutionA solution of 1-propanol

(1 in 2000).
Column: A glass column, about 3.2 mm in inside diameter and about 1.5 m in length, packed with porous
ethylvinylbenzene-divinylbenzene copolymer for gas
chromatography (0.0075 m in average pore size, 500 ~
600 m2/g in specific surface area 150 ~ 180 m in particle diameter)
Column temperature: A contant temperature of about
135 o C .
Carrier gas: Nitrogen
time of ethanol is about 5 minutes.
pH The pH of a solution obtained by suspending 0.1 g
of Doxycycline Hyclate Hydrate in 10 mL of water is be-
tween 2.0 and 3.0.

Assay DoxycyclineWeigh accurately an amount of
Doxycycline Hyclate Hydrate and Doxycycline Hyclate
Hydrate RS, equivalent to about 0.1 g (potency), dissolve
each in water and make exactly 100 mL, and use these
Perform the test with exactly 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak areas, AT and AS,
of doxycycline.
Amount [g (potency)] of doxycycline (C22H24N2O8)

= Amount [g (potency)] of Doxycycline RS
AT
AS
octadecylsilanized silica gel for liquid chromatography(10 m in particle diameter) with a guard column,
about 4.6 mm in inside diameter and 30 mm in length,
chromatography.
Mobile phase: Adjust the pH of a mixture of 0.1
mol/L sodium phosphate solution, ethanol and N,Ndimethyl-n-octylamine (450:500:3) to between 6.2 and
6.3 with phosphoric acid
Doxycycline Hydrate
OH
OH
O
OH
NH2
H2O
OH
H
H
CH3
H
OH
N(CH3)2
C22H24N2O8H2O: 462.45
Doxycycline Hydrate contains not less than 880 g (potency) and not more than 980 g (potency) per mg of
doxycycline (C22H24N2O8: 444.44), calculated on the anhydrous basis
Description Doxycycline Hydrate is yellow crystalline
powder.
Doxycycline Hydrate is sparingly soluble in ethanol,
KP 9 333
very slightly soluble in water, and practically insoluble in
chloroform or in ether.
Doxycycline Hydrate dissolves in dilute acid solution or
alkaline solution.
Identification Determine the infrared spectra of Doxycycline Hydrate and Doxycycline RS, as directed in the
potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities of
H3C
CH2CH3
H
H
H3C
H3C
H

g of Doxycycline Hydrate in 10 mL of water is between
5.0 and 6.5.
Assay Weigh accurately an amount of Doxycycline
Hydrate and Doxycycline RS, equivalent to about 0.1 g
(potency), dissolve each in 24 mL of 0.1 mol/L hydrochloric acid TS and mobile phase to make exactly 100 mL,
and use these solutions as the test solution and the standard solution. Perform the test with exactly 10 L each
under the Liquid Chromatography according to the following operating conditions, and determine the peak
areas, AT and AS , of doxycycline.
Amount [g (potency)] of doxycycline (C22H24N2O8)

AT
AS
(10 m in particle diameter) with a guard column, about
4.6 mm in inside diameter and 30 mm in length, packed
with octadecylsilanized silica gel for liquid chromatography.
Mobile phase: Adjust the pH with phosphoric acid of
a mixture of 0.1 mol/L sodium phosphate solution, methanol and N,N-dimethyl-n-octylamine (450:500:3) to
between 6.2 and 6.3 with phosphoric acid
tight containers.
= Amount [g (potency)] of doxycycline RS
Drostanolone Propionate
Preserve in lisht-resistant,
C23H36O3: 360.53
Drostanolone Propionate, when dried, contains not less
than 97.0% and not more than 103.0% of drostanolone
propionate (C23H36O3).
Description Drostanolone Propionate is a white to yellowish white, crystalline powder and is odorless or has a
faint, characteristic odor.
Drostanolone Propionate is very soluble in chloroform,
freely soluble in ether, sparingly soluble in ethanol and
Identification (1) Dissolve 20 mg of Drostanolone
Propionate in 1 mL of ethanol, add 1 mL of alkaline hydroxylamine TS, allow to stand for 10 minutes and add 1
mL of hydrochloric acid-ethanol TS and 1 mL of ferric
chloride TS: a dark red color is observed.
(2) Take 10 mg of Drostanolone Propionate, add 10
mL of freshly prepared vanillin-sulfuric acid TS and dissolve by heating on a water-bath for 5 minutes: a redpurple color is observed.
(3) Determine the infrared spectra of Drostanolone
Propionate and Drostanolone Propionate RS, previously
under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve each Drostanolone Propionate and Drostanolone Propionate RS in
chloroform, evaporate to dryness and repeat the test on
the residues.
28 (after drying, 0.2 g, chloroform, 10 mL, 100 mm).
Melting Point

0.20 g of Drostanolone Propionate in 10 mL of chloroform: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Drostanolone Propionate according to Method 2 and perform the
(3) Related substancesDissolve 50 mg of Drostanolone Propionate in 5 mL of chloroform and use this so-

lution as the test solution. Pipet 1.0 mL of the test solution, add chloroform to make exactly 100 mL and use
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of heptane and ethyl acetate
Develop the plate with the same solvent again and airdry the plate. Spray vanillin-sulfuric acid TS on the plate
and heat at 105 C for 5 minutes: the spots other than the

tight containers.
Drostanolone Propionate
Injection
Drostanolone Propionate Injection is an oily solution for
injection. Drostanolone Propionate Injection contains not
amount of drostanolone propionate (C23H36O3: 360.53).

P2O5, 50 C, 2 hours).
Method of Preparation Prepare as directed under Injections, with Drostanolone Propionate.
Description Drostanolone Propionate Injection is a

clear, colorless to pale yellow, oily liquid.
Assay Weigh accurately about 25 mg of Drostanolone

Propionate and Drostanolone Propionate RS, previously
dried, dissolve each in exactly 5 mL of the internal standard solution, add chloroform to make 10 mL and use
the Gas Chromatography according to the following
peak area of drostanolone propionate to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of drostanolone propionate(C23H36O3)

= amount (mg) of Drostanolone Propionate RS
QT
QS
Internal standard solutionA solution of Cholesterol in chloroform (1 in 200).

earth for gas chromatography (125 m to 150 m in particle diameter) coated with 50% phenylmethyl silicon polymer for gas chromatography at the ratio of 3%.
about 260 C.
time of drostanolone propionate is about 8 minutes.
Selection of Column: Proceed with 2 L of the standard solution as directed under the above operating conditions, and calculate the resolution. Use a column giving
elution of drostanlone propionate and the internal standard in this order with the resolution between their peaks
Identification Take a volume of Drostanolone Propionate Injection, equivalent to 50 mg of Drostanolone Propionate according to the labeled amount, add 20 mL of
diluted methanol (4 in 5), shake for 5 minutes and centrifuge. Evaporate 5 mL of the supernatant liquid on a water-bath to dryness under a current of air. Dissolve the residue in 2 mL of chloroform and use this solution as the
test solution. Separately, dissolve 5 mg of Drostanolone
Propionate RS in 1 mL of chloroform and use this solution as the standard solution. Perform the test with the
with a mixture of heptane and ethyl acetate (9 : 1) to a
evenly vanillin-sulfuric acid TS on the plate and heat at
105 C for 5 minutes: the principal spot from the test solution and the spot from the standard solution show the
same color tone and Rf value.
It

Assay (1) Chromatographic tubeUse a glass tube,
about 20 mm in inside diameter and about 23 cm in
length. Place a small amount of absorbent cotton in the
bottom of the tube and put sea sand, 5 mm in height on it.
(2) Chromatographic columnMoisten 10 g of 4%
hydrated alumina neutral thoroughly with 15 to 20 mL of
KP 9 335
hexane and mix gently. Wash with hexane down to the
chromatographic tube and pack by flowing out the solution. Place sea sand, 5 mm in height on it and fill with
hexane up to the surface of sea sand.
(3) Standard solutionWeigh accurately about 25
mg of Drostanolone Propionate RS, previously dried in a
desiccator (in vacuum, P2O5, 50 C) for 2 hours and dissolve in exactly 10 mL of the internal standard solution.
(4) Test stock solutionPipet a volume of Drostanolone Propionate Injection, equivalent to about 50 mg
of Drostanolone Propionate (C23H36O3) and add hexane
to make exactly 20 mL.
(5) ProcedurePipet 5 mL of the test stock solution
into the previously prepared chromatographic column
and elute to the surface of sea sand. Wash the inner side
of the chromatographic tube with two 5 mL volumes of
hexane, elute to the surface of sea sand, then elute 120
mL of a mixture of hexane and ethyl acetate (50 : 1) at
the rate of 7 to 8 mL per minute and discard the effluent
solution. Elute 150 mL of a mixture of hexane and ethyl
acetate (20 : 1) at the rate of 7 to 8 mL per minute and
collect the effluent solution. After elution, wash the bottom part of the chromatographic tube with a small volume of hexane, combine the washing with the effluent
solution and evaporate the solvent at below 30 C. To the
residue, add exactly 5 mL of the internal standard solution and use this solution as the test solution. When the
procedure is run with 2 L each of the test solution and
the standard solution as directed in the Assay under
Drostanolone Propionate.
Amount (mg) of drostanolone propionate (C23H36O3) =
amount (mg) of Drostanolone Propionate RS
QT
2
QS
Internal standard solutionA solution of Cholesterol in chloroform (1 in 400).


Dydrogesterone
O
H3C
CH3
H
H3C
C21H28O2: 312.45
Dydrogesterone when dried, contains not less than 98.0%
and not more than 102.0% of dydrogesterone (C21H28O2).
Description Dydrogesterone is a white to pale yellowish white crystal or crystalline powder and is odorless.
Dydrogesterone is freely soluble in chloroform, soluble
in acetonitrile, sparingly soluble in methanol or in ethanol, slightly soluble in ether and practically insoluble in
water.
.
Identification (1) Take 5 mg of Dydrogesterone, add 5
mL of p-anisaldehyde-acetic acid TS and 2 to 3 drops of
sulfuric acid and heat in a water-bath for 2 minutes: an
orange-red color is observed .
Dydrogesterone and Dydrogesterone RS in methanol (1
(3) Determine the infrared spectra of Dydrogesterone
and Dydrogesterone RS, previously dried, as directed in
D : Between - 47 and 50 (after drying, 0.1 g, chloroform, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Dydrogesterone according to Method 2 and perform the test.
(2) Related substancesDissolve 10 mg of Dydrogesterone in 200 mL of the mobile phase and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add the mobile phase to make exactly 100 mL and
method: the total area of peaks other than the peak of
Dydrogesterone from the test solution is not larger than
that of Dydrogesterone from the standard solution.
about 40 C.
Mobile phase: A mixture of water, ethanol and acetonitrile (53 : 26 : 21).
time of Dydrogesterone is about 12 minutes.
System suitability

System performance: Dissolve 1 mg of Dydrogesterone and Progesterone in 20 mL of the mobile phase.
When the procedure is run with 10 L each of these solutions, as directed under the above operating conditions,
Dydrogesterone and Progesterone are eluted in this order
than 8.0. Wavelength is 265 nm.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Dydrogesterone obtained
from 10 L of the standard solution is between 5 mm and
10 mm.
the retention time of Dydrogesterone after the solvent
peak.
P2O5, 24 hours).
Assay Weigh accurately about 50 mg of Dydrogesterone, previously dried and dissolve in methanol to make
exactly 100 mL. Pipet 1.0 mL of this solution and add
methanol to make exactly 100 mL. Determine the absorbance, A, of this solution at the wavelength of a maximum absorption at about 286 nm as directed under the
Ultraviolet-visible Spectrophotometry.
Amount (mg) of dydrogesterone (C21H28O2)

A
= 845 100000
Dydrogesterone Tablets
Dydrogesterone Tablets contain not less than 95.0% and
not more than 105.0% of the labeled amount of dydrogesterone (C21H28O2: 312.45).
Method of Preparation Prepare as directed under Tablets, with Dydrogesterone.
Identification (1) Take a portion of powdered Dydrogesterone Tablets, equivalent to 50 mg of Dydrogesterone according to the labeled amount and add 50 mL of
methanol, shake well and filter. Evaporate 5 mL of the
filtrate on a water-bath to dryness. Proceed with the residue as directed in the Identification (1) under Dydrogesterone.
(2) Take 1 mL of the filtrate obtained in (1) and add
methanol to make exactly 200 mL. Determine the absorption spectra of this solution and a solution of Dydrogesterone RS in methanol (1 in 200000) as directed
same wavelengths.
Dissolution Test Take 1 tablet of Dydrogesterone Tablets and perform the test using 900 mL of water at 50
revolutions per minute according to Method 2 under the
Dissolution Test. After 30 minutes from the start of the
test, take 20 mL or more of the dissolved solution and filter. Discard the first 10 mL of the filtrate and use the
subsequent as the test solution. Separately, weigh accurately about 50 mg of Dydrogesterone RS, previously
dried in a desiccator (in vacuum, P2O5) for 24 hours and
dissolve in methanol to make exactly 100 mL. Pipet 1.0
mL of this solution, add water to make exactly 100 mL
the absorbance, AT and AS , of the test solution and
under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Dydrogesterone Tablets in 30 minutes is not less than 80%.

of dydrogesterone (C21H28O2) = W S
AT
1
9
AS C
WS : Amount (mg) of Dydrogesterone RS

C: Labeled amount
(C21H28O2) in 1 tablet.
(mg)
of
dydrogesterone

Dydrogesterone Tablets. Weigh accurately a portion of
the powder, equivalent to about 10 mg of dydrogesterone
(C21H28O2), and shake well with 50 mL of methanol and
add methanol to make exactly 100 mL. Filter this solution, discard the first 20 mL of the filtrate, pipet the subsequent 5.0 mL, add methanol to make exactly 100 mL
weigh accurately about 10 mg of Dydrogesterone RS
previously dried in a desiccator (in vacuum, P2O5) for 24
hours, proceed in the same manner as preparation of the
test solution and use this solution as this standard solution. Determine the absorbance, AT and AS , of the
Amount (mg) of dydrogesterone (C21H28O2)

= amount (mg) of Dydrogestrone RS
AT
AS
KP 9 337
Ebastine
H3C
CH3
CH3
than the area of the principal peak with the standard solution (2) (0.1%), the peak area of the other related substances are not more than that of the principal peak from
the standard solution (2) (0.1%). total area of all related
substances is not more than 4 times the area of the principal peak from the standard solution (2) (0.4%). Disregard the peak being not more than 0.5 times the area of
the principal peak with the standard solution (2).
O
O
C32H39NO2 : 469.66
Ebastine contains ano less than 99.0% and not more than
101.0% of ebastine (C32H39NO2), calculated on the anhydrous basis.
Description Ebastine is a white crystalline powder.
Ebastine is very soluble in dichloromethane, slightly soluble in methanol, and practically insoluble in water.
Identification Determine the infrared spectra of Ebastine and Ebastine RS, previously dried, as directed in the
potassium bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar
Purity (1) SulfatesWeigh 2.5 g of Ebastine, add 25
ml of dilute nitric acid, boil under reflux for 10 minutes,
cool and filter. Rinse the filter paper and the residue with
adequate amount of water, combine with filtrate, add water to make exactly 50 mL and perform the test using this
mixing 0.53 mL of 0.005 mol/L sulfuric acid VS and 25
mL of dilute nitric acid and adding water to make 50 mL.
(0.01%).
(2) Related substancesKeep the test solution and
the standard solution of this test protected from light.
Dissolve 0.125 g of Ebastine in mobile phase to make 50
mL and use this solution as the test solution. Dissolve 5.0
mg of Ebastine Related Substance III [4(Diphenylmethoxy)piperidine] RS and 5.0 mg of Ebastine Related Substance IV {1-[4-(1,1-Dimethylethyl)
phenyl]-4-(4-hydroxypiperidine-1-yl)butan-1-one] RS in
mobile phase to make exactly 20 mL, pipet 1.0 mL of
this solution, add mobile phase to make exactly 100 mL
and use this solution as the standard solution (1). To 1.0
mL of the test solution add mobile phase to make exactly
100 mL, pipet 1.0 mL of this solution, add mobile phase
to make exactly 10 mL and use this solution as the standard solution (2). Perform the test with exactly 10 L
each of the test solution and the standard solutions (2) as
following conditions, and determine each peak area by
the automatic integration method: any peak area of related substances I, II, III, IV, V, VI, and VII in the chromatogram obtained with the test solution is not more
nitrile silica gel for Liquid Chromatography (5 m in
particle diameter).
Mobile phase: A mixture of phosphate buffer and
acetonitrile (65 : 35). Adjust the percentage of acetonitrile to between 30% and 40% so that the retention time
of ebastine is about 110 min.
System suitability
condition, relative retention time of related substances I,
II, III, IV, V, VI, and VII with reference to ebastine are
0.04, 0.05, 0.20, 0.22, 0.42, 0.57 and 1.14, respectively.
When the procedure is run with 10 L of the standard solution (1) under the above operating condition, the resolution between the peaks of related substance IV and related substance III is not less than 2.0.
Run time: 1.4 times the retention time of ebastine.
Phosphate bufferAdjust pH of 0.06w/v% phosphoric acid with 4w/v% sodium hydroxide to pH 5.0.
direct titration).
Assay Weigh accurately about 0.35 g of Ebastine, add
50 ml of glacial acetic acid and titrate with 0.1 mol/L

= 46.97 mg of C32H39NO2.
Ecothiopate Iodide
CH3
O
CH3CH2O
CH3CH2O
SCH2CH2
CH3
CH3
C9H23INO3PS: 383.23
Ecothiopate Iodide contains not less than 95.0% and not
more than 101.0% of ecothiopate iodide (C9H23INO3PS),
Description Ecothiopate Iodide is a white crystal or
crystalline powder.
Ecothiopate Iodide is very soluble in water, freely soluble in methanol, slightly soluble in ethanol, and practically insoluble in ether.
Identification (1) Dissolve 0.1 g of Ecothiopate Iodide
in 2 mL of water, and add 1 mL of nitric acid: a brown
precipitate is produced. To 1 drop of the turbid solution
containing this precipitate, add 1 mL of hexane and
shake: a light red color is observed in hexane.
(2) Heat the suspension of the precipitate obtained in
(1) until it becomes colorless, cool, add 10 mL of water
and use this solution as the test solution. 2 mL of the test
solution responds to the Qualitative Tests (2) for phosphate.
(3) 2 mL of the test solution obtained in (2) responds
to the Qualitative Tests for sulfate.
pH Dissolve 0.1 g of Ecothiopate Iodide in 40 mL of
water: the pH of this solution is between 3.0 and 5.0.
Melting Point
(3) Related substancesDissolve 0.20 g of Ecothiopate Iodide in 10 mL of methanol and use this solution
as the test solution. Pipet exactly 3 mL of the test solution, add methanol to make exactly 200 mL and use this
the test and the standard solution on a plate of cellulose
mixture of n-butanol, water and glacial acetic acid (4 : 2 :
Spray evenly Dragendorffs TS for spraying on the plate:
any spot other than the principal spot from the test solution are not more intense than that from the standard solution.
P2O5, 50 C, 3 hours).
Assay Weigh accurately about 0.125 g of Ecothiopate
Iodide and dissolve in water to make exactly 100 mL.
Pipet exactly 10 mL of this solution, add 30 mL of water,
then add exactly 10 mL of phosphate buffer solution, pH
12, stopper the container and allow to stand at 25 3 C
for 20 minutes. To this solution, add quickly 2 mL of
glacial acetic acid and titrate with 0.002 mol/L iodine VS
Titrimetry). Perform the test in the same manner without
phosphate buffer solution, pH 12 and make any necessary correction.

= 1.5329 mg of C9H23INO3PS
tight containers. Store at not more than 0 C.

g of Ecothiopate Iodide in 5 mL of water: the solution is
(2) Heavy metalsTake 1.0 g of Ecothiopate Iodide
in a Kjeldahl flask, add 5 mL of nitric acid and 2 mL of
sulfuric acid, put a small funnel on the mouth of the flask
and heat carefully until white fumes are evolved. After
cooling, add 2 mL of nitric acid and heat. Repeat this
procedure twice, add several 2 mL volumes of strong hydrogen peroxide water and heat until the solution becomes colorless and white fumes are evolved. After cooling, transfer the solution together with a small volume of
water to a Nessler tube and add water to make about 20
mL. Adjust the solution with strong ammonia water and
ammonia TS to a pH between 3.0 and 3.5, add water to
proceed in the same manner as the preparation of the test
solution and add 2.0 mL of standard lead solution and
water to make 50 mL (not more than 20 ppm).
Edrophonium Chloride
CH3
N
C2H5
Cl
CH3
HO
C10H16ClNO: 201.69
Edrophonium Chloride, when dried, contains not less
than 98.0% and not more than 101.0% of edrophonium
chloride (C10H16ClNO).
Description Edrophonium Chloride is a white crystal
Edrophonium Chloride is very soluble in water, freely
soluble in ethanol or in glacial acetic acid, and practically insoluble in acetic anhydride or in ether.
Edrophonium Chloride is hygroscopic.
KP 9 339
Edrophonium Chloride is gradually colored by light.
Identification (1) Take 5 mL of a solution of Edrophonium Chloride (1 in 100) and add 1 drop of ferric chloride TS: a light red-purple color is observed.
(2) Determine absorption spectra of solutions of
Edrophonium Chloride and Edrophonium Chloride RS,
in 0.1 mol/L hydrochloric acid TS (1 in 20000) as directed under the Ultraviolet-visible Spectrophotometry:
(3) A solution of Edrophonium Chloride (1 in 50) responds to the Qualitative Tests for chloride.
Melting Point
composition).
pH Dissolve 1.0 g of Edrophonium Chloride in 10 mL

g of Edrophonium Chloride in 10 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Edrophonium Chloride according to Method 1 and perform the
Edrophonium Chloride according to Method 1 and perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.50 g of Edrophonium Chloride in 10 mL of ethanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution and add ethanol to make exactly 100 mL. Pipet
exactly 3 mL of this solution, add ethanol to make exactly 10 mL and use this solution as the standard solution.
solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with
a mixture of methanol, chloroform and strong ammonia
water (16 : 4 : 1) to a distance of about 10 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot other than the principal spot
from the test solution is not more intense than that from
P2O5, 3 hours).
Assay Weigh accurately about 0.2 g of Edrophonium
Chloride, previously dried, and dissolve in 100 mL of a
mixture of acetic anhydride and glacial acetic acid (7 : 3).
Titrate with 0.1 mol/L perchloric acid VS (potentiometic
titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary cor-
rection.
= 20.169 mg of C10H16ClNO
tight containers.
Edrophonium Chloride
Injection
Edrophonium Chloride Injection is an aqueous solution
for injection. Edrophonium Chloride Injection contains
not less than 95.0% and not more than 105.0% of the labeled amount of edrophonium chloride (C10H16ClNO:
201.69).
Method of Preparation Prepare as directed under Injections, with Edrophonium Chloride.
Description Edrophonium Chloride Injection is a clear,
colorless liquid.
Identification (1) Take a volume of Edrophonium
Chloride Injection, equivalent to 40 mg of Edrophonium
Chloride according to the labeled amount, add 4 mL of
barium nitrate TS, shake and filter. Proceed with the filtrate as directed in the Identification (1) under Edrophonium Chloride.
(2) Determine the absorption spectrum of the test solution obtained in the Assay as directed under the Ultraviolet-visible Spectrophtometry: it exhibits a maximum
It

Assay Perform this procedure without exposure to daylight, using light-resistant containers. Take exactly a volume of Edrophonium Chloride Injection, equivalent to
about 50 mg of Edrophonium Chloride, place in a chromatographic column prepared by pouring 10 mL of
weakly basic DEAE-bridged dextran anion exchanger
(C1 type) (50 m to 150 m in particle diameter) into a
chromatographic tube, about 2 cm in inside diameter and
about 10 cm in length, add 25 mL of water and elute at

the flow rate of 1 to 2 mL per minute. Wash the column
with two 25 mL volumes of water at the flow rate of 1 to
2 mL per minute. Combine the washings with above effluent solutions and add water to make exactly 100 mL.
Pipet exactly 10 mL of this solution and add 10 mL of
phosphate buffer solution, pH 8.0 and 5 g of sodium
chloride. Wash this solution with four 20 mL volumes of
a mixture of ether and hexane (1 : 1), collect the water
layer, add 0.1 mol/L hydrochloric acid TS to make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately about 50 mg of Edrophonium
Chloride RS, previously dried in a desiccator (in vacuum,
P2O5) for 3 hours and dissolve in water to make exactly
100 mL. Pipet exactly 10 mL of this solution and prepare
the standard solution in the same manner as the test solution. Determine the absorbances, AT and AS , of the
Amount (mg) of edrophonium chloride (C10H16ClNO)
= amount (mg) of Edrophonium Chloride RS
AT
AS

Elcatonin
H
Ser
Asn
Leu
Ser
Thr
Val
NH
Leu
Gly
Lys
Leu
Ser
Gln
Gly
Glu
Ala
Leu
Gly
His
Thr
Lys
Pro
Leu
Gln
Thr
Pro
Arg
Thr
Asp
Val
NH2
C148H244N42O47 : 3363.77
Elcatonin contains not less than 5000 Elcatonin Units
and not more than 7000 Elcatonin Units per 1 mg of peptide, calculated on the dehydrated and de-acetic acid
bases.
Description Elcatonin is a white powder.
Elcatonin is very soluble in water, freely soluble in ethanol, and practically insoluble in acetonitrile.
Elcatonin is hygroscopic.
The pH of its solution (1 in 500) is between 4.5 and 7.0.
Identification Dissolve 5 mg each of Elcatonin and
Elcatonin RS in 5 mL of water. Determine the absorption
spectra of both solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
Constituent Amino Acids Put about 1 mg of Elcatonin

in a test tube for hydrolysis, add phenol-hydrochloric acid TS to dissolve, replace the air inside with Nitrogen,
seal the tube under reduced pressure, and heat at 110 2
C for 24 hours. After cooling, open the tube, evaporate
the hydrolyzate to dryness under reduced pressure, dissolve the residue in 1 mL of 0.02 mol/L hydrochloric acid TS, and use this solution as the test solution. Separately, weigh exactly 1.33 mg of L-aspartic acid, 1.19 mg of
L-threonine, 1.05 mg of L-serine, 1.47 mg of L-glutamic
acid, 1.15 mg of L-proline, 0.75 mg of glycine, 0.89 mg
of L-alanine, 1.17 mg of L-valine, 1.89 mg of L-tyrosine,
1.83 mg of L-lysine hydrochloride, 2.10 mg of Lhistidine hydrochloride monohydrate and 2.11 mg of Larginine hydrochloride, dissolve them in 0.02 mol/L hydrochloric acid TS to make exactly 50 mL, and use this
exactly 10 L each of the test solution and the standard
solution as the following conditions: 14 peaks of amino
acids appear on the chromatogram obtained from the test
solution, and their respective molar ratios against alanine
are 1.7 2.2 for aspartic acid, 3.5 4.2 for threonine, 2.4
3.0 for serine, 2.7 3.2 for glutamic acid, 1.7 2.2 for
proline, 2.7 3.2 for glycine, 1.6 2.2 for valine, 0.8
1.2 for 2-aminosuberic acid, 4.5 5.2 for leucine, 0.7
1.2 for tyrosine, 1.7 2.2 for lysine, 0.8 1.2 for histidine and 0.7 1.2 for arginine.
Detector: A visible spectrophotometer (wavelength:
440 nm and 570 nm).
Column: A stainless steel column about 4 mm in inside diameter and about 8 cm in length, packed with
strongly acidic ion-exchange resin for liquid chromatography composed with a sulfonated styrenedivinylbenzene copolymer (3 m in particle diameter).
Column temperature: Varied between 50 C and 65
C.
Chemical reaction vessel temperature: A constant
temperature of about 130 C.
Color developing time: About 1 minute.
Mobile phase: Buffer solutions A, B, C and D, with
sodium ion concentrations of 0.10 mol/L, 0.135 mol/L,
1.26 mol/L and 0.20 mol/L, respectively. The ion concentration of the mobile phase is changed stepwise from
0.10 mol/L to 1.26 mol/L by using these buffer solutions.
Components of buffer solutions (g)
Buffer solution
Citric acid
8.85
7.72
6.10
Sodium citrate
3.87
10.05
26.67
2.50
8.00
3.54
1.87
54.35
Sodium hydroxide
Sodium chloride
KP 9 341
Ethanol
60.0 mL
60.0 mL
Thiodiglycol
5.0 mL
5.0 mL
Purified water
q.s.
q.s.
q.s.
q.s.
Total amount
1000 mL 1000 mL 1000 mL 1000 mL
Reaction reagent: Mix 407 g of lithium acetate dehydrate, 245 mL of glacial acetic acid and 801 mL of 1methoxy-2-propanol, add water to make 2000 mL, stir
for about 20 minutes while passing Nitrogen, and use
this solution as solution A. Separately, to 1957 mL of 1methoxy-2-propanol, add 77 g of ninhydrin and 0.134 g
of sodium borohydride, stir for about 20 minutes while
passing Nitrogen, and use this solution as solution B.
Mix solution A and solution B before use.
Flow rate of mobile phase: Adjust the flow rate so
that the retention time of arginine is about 75 minutes.
Flow rate of reaction reagent: About 0.2 mL per
minute.
Selection of column: Proceed with 10 L of the standard solution under the above operating conditions. Use
a column from which aspartic acid, threonine, serine,
glutamic acid, praline, glycine, alanine, valine, 2aminosuberic acid, leucine, tyrosine, lysine, histidine and
arginine are eluted in this order, with complete separation
of each peak.
Purity (1) Acetic acidWeigh accurately about 3 6
mg of Elcatonin quickly under conditions of 25 2 o C
and 50 5% relative humidity, add exactly 1 mL of the
internal standard solution to dissolve it, and use this solution as the test solution. Separately, weigh accurately
about 0.5 g of glacial acetic acid, and add the internal
standard solution to make exactly 100 mL. Pipet 5 mL of
this solution, add the internal standard solution to make
exactly 100 mL, and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate the ratios, QT and QS , of the peak
area of acetic acid to that of the internal standard: the
amount of acetic acid is not more than 7.0%.
Amount (%) of acetic acid (CH3COOH)

= W ST Q T 50
W SA
QS
WST : Amount (g) of glacial acetic acid

WSA : Sample amount (mg)
Internal standard solutionA solution of citric acid

(1 in 4000).
Detector: An ultraviolet absorption photometer (wa-
velength: 210 nm)

Column: A stainless steel column abut 4 mm in inside
diameter and about 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m
about 25 C.
Mobile phase: Dissolve 13.2 g of diammonium hydrogen phosphate in 900 mL of water, add phosphoric
acid to adjust the pH to 2.5, and add water to make 1000
mL.
time of acetic acid is about 4 minutes.
System suitanility
with 20 L of the standard solution under the above operating conditions, acetic acid and citric acid are eluted
in this order with the resolution between their peaks being not less than 2.0.
(2) Related substancesDissolve 1.0 mg of Elcatonin in 1 mL of a mixture of trifluoroacetic acid TS and
acetonitrile (2:1), and use this solution as the test solution. Take exactly 0.3 mL of the test solution, add a mixture of trifluoroacetic acid TS and acetonitrile (2:1) to
make exactly 10 mL, and use this solution as the standard solution. Perform the test with exactly 10 L each
under the Liquid Chromatography according to the following conditions, and determine each peak area by the
automatic integration method: the total of the peak areas
other than the peak of elcatonin of the test solution is not
larger than the peak of elcatonin of the standard solution,
and each peak area other than the peak of elcatonin of the
test solution is not larger than 1/3 of the peak area of elcatonin from the standard solution.
Column: A stainless steel column abut 4 mm in inside
diameter and about 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m
about 40 C.
Mobile phase: A mixture of trifluoroacetic acid TS
and acetonitrile (change the ratio linearly from 85:15 to
55:45 in 30 minutes).
time of elcatonin is about 25 minutes.
System suitability
System performance: Dissolve 2 mg of Elcatonin
in 200 L of trypsin TS for test of elcatonin, warm at 37
C for 1 hour, then add 1 drop of glacial acetic acid, and
heat at 95 C for 1 minute. To 10 L of this solution, add
50 L of the test solution, and mix. Proceed with 10 L
of this solution under the above operating conditions, and
calculate the resolution. Use a column such that the reso-

lution between the peak of elcatonin and the peak which
appears immediately before the peak of elcatonin is not
less than 2.0, and the retention time of elcatonin is about
25 minutes.
Time span of measurement: Continue measurement until the regularly changing baseline of the chromatogram disappears, beginning after the solvent peak.
Water Weigh accurately 1 3 mg of Elcatonin quickly
under conditions of 25 2 C and 50 5% relative humidity, and perform the test as directed in the coulometric titration under the Water Determination: not more
than 8.0%
Nitrogen Content Weigh accurately 15 20 mg of Elcatonin quickly under conditions of 25 2 C and 50
5% relative humidity, and perform the test as directed
under the Nitrogen Determination: it contains not less
than 16.1% and not more than 18.7% of nitrogen (N:
14.01) in the peptide, calculated on the dehydrated and
de-acetic acid basis.
Assay (i) Aminals: Select healthy male SpragueDawley rats each weighing between 90 g and 110 g.
Keep the rats for not less than 3 days before use, providing an appropriate uniform diet and water.
(ii) Diluent for elcatonin: Dissolve 2.72 g of sodium
acetate in water to make 200 mL, add 0.2 g of bovine serum albumin, and adjust the pH to 6.0 with glacial acetic
acid. Prepare before use.
(iii) Standard solution: Dissolve Elcatonin RS in the
diluent for elcatonin to make two standard solutions, one
to contain exactly 0.75 Unit in each mL which is designated as the high-dose standard solution, SH , and the
other to contain exactly 0.0375 Unit in each mL which is
designated as the low-dose standard solution, S L .
(iv) Test solution: Weigh accurately 0.5 2.0 mg of Elcatonin quickly under conditions of 25 2 C and 50
5% relative humidity, and dissolve in the diluent for elcatonin to make two test solutions, the high-dose test solution, TH , which contains the Units per mL equivalent to
S H and the low-dose test solution, TL , which contains
the Units per mL equivalent to S L .
(v) Deproteinizing solution for elcatonin: Dissolve
160 g of trichloroacetic acid and 30.6 g of strontium
chloride in water to make 3600 mL.
(vi) Procedure: Divide the animals into 4 equal
groups of not less than 10 animals each. Withhold all
food, but not water, for 18 to 24 hours before the injection, and withhold water during the assay until the final
blood sample is taken. Handle the animals with care in
order to avoid undue excitement.
Inject exactly 0.2 mL each of the standard solutions
and the test solutions into the tail vein of each animal as
indicated in the following design:
First group
SH
Third group
TH
Second group
SL
Fourth group
TL
At 1 hour after the injection, take a sufficient amount

blood sample to perform the test from the carotid artery
and vein of each animal under ether anesthesia, centrifuge the blood samples to separate serum, and determine
the serum calcium according to the following (vii).
(vii) Serum calcium determination: Take exactly 0.3
mL of the serum, add the deproteinizing solution for elcatonin to make exactly 3 mL, mix well, centrifuge, and
use the supernatant liquid as the test solution for calcium
determination. Separately, pipet 1 L of Standard Calcium
Solution for the Atomic Absorption Spectrophotometry,
and add a solution of sodium chloride (17 in 2000) to
make exactly 10 mL. Pipet 5 mL of this solution, add the
deproteinizing solution for elcatonin to make exactly 50
mL, and use this solution as the standard solution for calcium determination. Determine the absorbances, AT
and AS , of the test solution and the standard solution as
directed under the Atomic Absorption Spectrophotometry
according to the following conditions. Determine the absorbance, A0 , of a solution obtained in the same manner
used for preparation of the standard solution, but with 1
mL of water instead of the standard solution.
Amount (mg) of calcium in 100 mL of the serum
= 0 .01
AT A 0
10 100
AS A0
Gas: Combustible gasAcetylene

Supporting gasAir
Lamp: Calcium hollow-cathode lamp
(viii) Calculation: Amounts of calcium in 100 mL of
the serum obtained with SH , S L , TH and TL in (vii)
are symbolized as y1 , y2 , y3 and y4 , respectively.
Sum up individual y1 , y2 , y3 and y4 to obtain Y1 , Y2 ,
Y3 and Y4 , respectively.
Units per mg of peptide, calculated on the dehydrated
and de-acetic acid basis
= antilog M (units per mL of SH) (b/a)
M = 0.3010
Ya
Yb
Ya = Y1 Y2 + Y3 + Y4
Yb = Y1 Y2 + Y3 Y4
a: Amount (mg) of the sample

{ 100
[water content (%) + acetic acid content (%)]

}
100
b: Total volume (mL) of the high-dose test solution

prepared by dissolving the sample with diluent for elcatonin
F computed by the following equation should be
KP 9 343
smaller than F shown in the table against n with which
s 2 is calculated. Calculate L (P = 0.95) by use of the following equation: L should be not more than 0.20. If F
exceeds F, or if L exceeds 0.20, repeat the test, increasing the number of animals or arranging the assay conditions so that F is not more than F and L is not more than
0.20.
Emetine Hydrochloride
CH3
H
N
HN
2 HCl
(Y1 + Y2 + Y3 Y4 )2
4 fs2
f: Number of the animals of each group.
y
y2
f
s2 =
n
F' =
OCH3
C29H40N2O42HCl: 553.56
Y = Y12 + Y22 + Y32 + Y42

n = 4( f 1)
C=
OCH3
OCH3
y : The sum of squares of y1 , y2 , y3 and y4 in

each group.
H3CO
L = 2 ( C 1 )( CM
+ 0.09062)
Yb2
Yb2 4 fs 2 t 2
t 2 : Value shown in the following table against n

used to calculate s 2 .
t2 = F
t2 = F
t2 = F
161.45
13
4.667
25
4.242
18.51
14
4.600
26
4.225
10.129
15
4.543
27
4.210
7.709
16
4.494
28
4.196
6.608
17
4.451
29
4.183
5.987
18
4.414
30
4.171
5.591
19
4.381
40
4.085
5.318
20
4.351
60
4.001
5.117
21
4.325
120
3.920
10
4.965
22
4.301
3.841
11
4.844
23
4.279
12
4.747
24
4.260

and store at temperate not exceeding 8 C.
Emetine Hydrochloride is the hydrochloride of an alkaloid obtained from Ipecac, or prepared by methylation of
cephaeline, or prepared synthetically. Emetine Hydrochloride contains not less than 98.0% and not more than
101.5% of emetine hydrochloride (C29H40N2O42HCl),
Description Emetine Hydrochloride is a white and
pale yellow crystalline powder with no odor.
Emetine Hydrochloride is freely soluble in water or
ethanol.
Emetine Hydrochloride is affected by light.
Identification (1) Determine the ultraviolet absorption
spectra of solutions Emetine Hydrochloride and Emetine
Hydrochloride RS in 0.25 mol/L sulfuric acid (1 in
20000) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Emetine Hydrochloride and Emetine Hydrochloride RS as directed in
(3) An aqeous solution (1 in 20) of Emetine Hydrochloride responds to the Quantitative Tests for chloride.
Purity (1) AcidityDissolve 0.1 g of Emetine Hydrochloride in 10 mL of water, add 1 drop of methyl red
TS and titrate with 0.020 mol/L sodium hydroxide VS:
Less than 0.5 mL is required to observe a yellow color.
(2) CephaelineDissolve 0.1 g of Emetine Hydrochloride in 10 mL of methanol and use this solution
as the test solution. Separately, dissolve 23 mg of cephaeline hydrobromide RS in 100 mL of methanol and
test with the test solution and the standard solution as directed under the Thinlayer Chromatography. Spot 10 L
each of the test solution and the standard solution on the
plate of silica gel for Thinlayer Chromatography. Develope the plate with a mixture of chloroform and diethylamine (9 : 1), until the solvent front upto about 12 cm.
Remove the plate from the tank and allow the plate to

dry in air for 20 minutes. Spray evenly the dried plate
with 2.5 mol/L sodium hydroxide VS and dry at 50 C
for 5 minutes. Then spray the plate with developing
agent: any cephaeline spot from the test solution is not
larger or not more intense than that from the standard solution (not more than 2%).
Developing reagentDissolve 0.3 g of p-nitroaniline
in 25 mL of 2 mol/L hydrochloric acid and cool to about
4 C. Slowly add 5 mL of sodium nitrite solution (1 in
25), maintaining the temperature at about 4 o C . Freshly
prepare the solution for each test.
Assay Weigh accurately about 0.15 g of Emetine Hydrochloride, dissolve in 5 mL of glacial acetic acid and
warm, if necessary. Allow to cool, add 10 mL of dioxane,
5 mL of mercuric acetate TS for nonaqeous titration and
titrate with 0.1 N perchloric acid VS(indiator : 3 drops of
methylrosaniline chloride TS). Perform a bland determination, and make any necessary correction.

= 27.678 mg of C29H40N2O42HCl
tight containers.
Emetine Hydrochloride Injection

Emetine Hydrochloride Injection is a sterile solution of
Emetine Hydrochloride in water for injection. Emetine
Hydrochloride Injection contains not less than 84.0% and
not more than 94.0% of the labeled amount of emetine
hydrochloride (C29H40-N2O42HCl: 553.56).
Method of Preparation Emetine Hydrochloride Injection is prepared as directed under Injections, with Emetine Hydrochloride.
Description Emetine Hydrochloride Injection is a clear
and colorless liquid.
Identification (1) Evaporate 1 mL of Emetine Hydrochloride Injection on a steam-bath to dryness: the residue responds to Identification (1) under Emetine Hydrochloride.
(2) The Emetine Hydrochloride Injection responds to
Identification (3) under Emetine Hydrochloride
Purity CephaelineEvaporate 1.0 mL of Emetine

Hydrochloride Injection on a steam-bath under nitrogen
to dryness. Dissolve the residue in a sufficient volume of
methanol to obtain the test solution having a concentration of 10 mg of Emetine Hydrochloride per mL. Separately, weigh 23 mg of Cephaelin Bromochloride RS,
add methanol to make 100 mL and use this solution as
the standard solution. Proceed as directed in the Purity
(2) for cepthaeline under Emetine Hydrochloride.
Bacterial Endotoxins Less than 5.4 EU/mg of emetine
hydrochloride.

Assay Transfer exactly a volume of Emetine Hydrochloride Injection, equivalent to about 0.12 g of emetine
hydrochloride (C29H40-N2O42HCl) according to the labeled amount, to a separatory funnel containing 20 mL of

water. Add ammonium hydroxide TS to become strongly
alkaline and to 0.5 mL of the water layer add hydrochloric acid to become weakly acidic, extract with ether until
it remains unaffected by the addition of 2 to 3 drops of
Meyers TS. Evaporate the combined ether extracts on a
water-bath. To the residue add 2 mL of neutralized ethanol and 30.0 mL of 0.01 mol/L sulfuric acid and warm
gently until the alkaloid is dissolved. Cool and titrate the
excess acid with 0.02 mol/L sodium hydroxide VS (indicator: 2 to 3 drops of methyl red). Perform a bland determination, and make any necessary correction.
Each mL of 0.01 mol/L sulfuric acid
= 5.536 mg of C29H40N2O42HCl
Enalapril Maleate
O
H
N
CO2H
CO2H
N
O
H
O
pH
It
H3C
CH3
CO2H
KP 9 345
C20H28N2O5C4H4O4: 492.52
Enalaprol Maleate contains not less than 98.0% and not
more than 102.0% of enalapril maleate (C20H28N2O5
C4H4O4), calculated on the dried basis.
.
Description Enalapril Maleate is white crystal or crystalline powder.
Enalapril Maleate is freely soluble in methanol, soluble
in water, and sparingly soluble in dichloromethane.
Enalapril Maleate dissolves in dilute sodium hydroxide
TS.
Identification (1) Retention time of main peak from
the test solution in the Assay is the same as that of the
standard solution
(2) Determine the Infrared spectrum of Enalapril Maleate and Enalapril Maleate RS, as directed in the paste
-43.5 (after drying, 0.1 g, methanol, 10 mL, 100 mm) .
Purity (1) Heavy metalsProceed with 2.0 g of Enalapril Maleate according to Method 2, and perform the
(2) Related substancesWeigh accurately about 30
mg of Enalapril Maleate, dissolve in a mixture of pH 2.5
phosphate buffer solution and acetonitrile (95 : 5) to
make exactly 100 mL. and use this solution as the test
Enalapril Maleate RS, dissolve in a mixture of pH 2.5
phosphate buffer solution and acetonitrile (95 : 5) to
make exactly 100 mL Pipet exactly 1 mL of this solution,
add a mixture of pH 2.5 phosphate buffer solution and
acetonitrile (95 : 5) to make exactly 100 mL and use this
50 L of the test solution and the standard solution as directed under the Liquid Chromatography according to
the following conditions. Determine the peak area by the
automatic integration method, calculate each amount of
related substances: among peaks other than the principal
peak one related substance is not more than 1.0%, another related substance is not more than 0.3% and the total
area of peaks of the related substances is not more than
2.0%.
Amount (%) of related substaced = 100 C S AT

Ci
AS
C S : the concentration of the standard solution

(mg/mL)
Ci : the concentration of Enalapril Maleate in the test
solution (mg/mL)
AT : Peak area of each related substances in test solu-
tion
AS : Peak area of each related substances in standard
solution
Proceed as directed in the operating conditions under
the Assay.
Loss on Drying Not more than 1.0 % (at a pressure not
exceeding 0.67 kPa, 60 C, 2 hours).
Assay Weigh accurately about 30 mg of Enalapril Maleate, dissolve in a mixture of pH 2.5 phosphate buffer
solution and acetonitrile (95 : 5) to make exactly 100 mL,
and use this solution as the test solution. Separately, dissolve about 30 mg, accurately weighed, of Enalapril Maleate in a mixture of pH 2.5 phosphate buffer solution
and acetonitrile (95 : 5) to make exactly 100 mL and use
with 50 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate the ratios, AT and AS , of the peak area of Enalapril Maleate
to that of the internal standard, for the test solution and
Amount (mg) of Enalapril Maleate (C20H28N2O5C4H4O4)

= amount (mg) of Enalapril Maleate RS
AT
AS
Ditector: An ultraviolet absorption photometer (wavelength: 254 nm).
diameter and about 15 cm in length, packed with styrenedivinyl benzene for liquid chromatography (5 m to
10 m in particle diameter).
Flow rate: 1.5mL/minute.
Mobile phase: Program as follows with the mobile
phase A and the mobile phase B in isocratic or linear
gradient.
The Mobile phase A: A mixture of pH 6.8 phosphate
buffer solution and acetonitrile (19 : 1)
The Mobile phase B: A mixture of acetonitrile and
pH 6.8 phosphate buffer solution (33 : 17)
Time (minutes)
0
0 to 20
20 to 25
25 to 26
Solution
A (%)
95
95 to 40
40
40 to 95
Solution
B (%)
5
5 to 60
60
60 to 5
Elution
equilibration
linear gradient
isocratic
linear gradient

26 to 30
95
isocratic
System suitability
System performance: Mix 1 mL of Enalapril diketopiperazine solution and 50 mL of the standard solution.
When the procedure is run with 50 L of this solution, as
directed under the above operating conditions, Enalapril
and enalapril diketopiperazine are eluted in this order
than 3.5.
times with the standard solution, as directed under the
above operating conditions, the relative standard deviation of the peak area is not more than 1.0%.
pH 6.8 phosphate buffer solution: Dissolve 2.8 g of monobasic sodium phosphate in about 900 mL of water in a
1000mL volumetric flask. Adjust with phosphoric acid to
a pH of about 6.8, dilute with water to volume, and mix.
pH 2.5 phosphate buffer solution: Dissolve 2.8 g of monobasic sodium phosphate in about 900 mL of water in a
Enalapril diketopiperazine solution: Place about 20
mg of Enalapril Maleate RS in a 100-mL beaker to form
a mound on the bottom of the beaker. Place the beaker on
a hot plate at about one-half the maximum hot plate temperature setting. Heat for about 5 minutes to 10 minutes
until the solid is melted. Immediately remove the beaker
from the hot plate, and allow to cool. Add 50 ml of acetonitrile, and sonicate for a few minutes to dissolve. The
solution typically contains, in each mL, between 0.2 mg
and 0.4 mg of enalapril diketopiperazine.
Enalapril Maleate Tablets

Enalapril Maleate Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of enalapril maleate (C20H28N2O5C4H4O4: 492.52).
Method of Preparation Prepare as directed under Tablets, with Enalapril Maleate.
Identification Retention time of main peak from the
test solution in the Assay is the same as those of the
standard solution
Dissolution Test Perform the test with 1 tablet of Enalapril Maleate Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of pH 6.8 phosphate buffer solution as a dissolution solution. Take 20 mL or more of the dissolved solution 30 minutes after starting the test, and filter through a
membrane filter with pore size of not more than 0.8 m.
Discard the first 10 mL of the filtrate, pipet the subse-
quent solution as the test solution. Separately, weigh accurately about 10 mg of Enalapril Maleate RS, dissolve
in pH 6.8 phosphate buffer solution to make exactly 100
mL and use this solution as the standard solution. Perform the test according to the operating conditions as directed in the Assay under Enalapril Maleate. The dissolution rate of Enalapril Maleate Tablets in 30 minutes is not
less than 80%.
of the Content Uniformity Test when the test is performed according to the following method. Take 1 tablet
of Enalapril Maleate Tablets, add 50 mL of pH 2.2 phosphate buffer solution, if necessary, sonicate for 15 mintes,
shake for 30 minutes, add pH 2.2 phosphate buffer solution to make exactly 100 mL and use this solution as the
test solution. Pipet exactly V mL each of this solution,
then add buffer solution to make a solution containing
0.1 mg/mL. Separately, weigh accurately about 10 mg of
Enalapril Maleate RS, add pH 2.2 phosphate buffer to
make exactly 100mL and use this solution as the standard solution. Perform the test according to the operating
conditions as directed in the Assay under Enalapril Maleate.
Amount (mg) of Enalapril Maleate (C20H28N2O5C4H4O4)

= T
C AT
D AS
T : labeled amount of Enalaptil Meleate in each tablet

(mg).
C : Concentration of the standard solution (mg/mL).
D : Concentration of Enalapril Maleate in the test solution (mg/mL).
AT : peak are of Enalapril Maleate in the test solution.
AS : peak area of Enalapril Maleate in the standard
solution
pH 2.2 phosphate bufferDissolve 1.38g of monobasic sodium phosphate in about 800 mL of water in a
Related Substances The test solution, the standard solution, pH 2.2 phosphate buffer solution and enalapril diketopiperazine solution are prepared as directed in the
Assay. Pipet 1.0 mL of the standard solution, add pH 2.2
phosphate buffer solution to make exactly 100mL and
use this solution as the related substances standard solution. Perform the test with 50 L of each of the test solution, the standard solution, the related substances standard solution and buffer solution as directed under the
Liquid Chromatography according to the assay method.
Determine each peak areas by the automatic integration
method, and calculate the amounts of related substances.
Measure the peak areas for all of the peak from the test
solution greater than 0.1% of enalapril of the response of
the peaks other than are not observed in the Buffer solu-
KP 9 347
tion.
Amount (%) of anhydrous enlalprilat
= 492 .53 CV AT 100
348 .39
AS
492.53: molecular weight of enalapril maleate

348.39: molecular weight of anhydrous enalaprilat
C : concentration Enalaprilat in the standard solution
(mg/mL)
V : nominal capacity of the test solution (mL)
N : number of tablets taken for the test
L : labeled amount of enalapril maleate in the tablet
AT : enalaprilat peak area obtained from the test solution
AS : enalaprilat peak area obtained from the standard
solution
Amount (%) of enalapril ketopiperazine
492 .53 C 'V
100
AT
=
358 .44
N 1.25 AS
L
492.53: molecular weight of enalapril maleate
358.44: molecular weight of enalapril ketopiperazine
C': concentration of Enalapril Maleate RS in the related substances standard solution (mg/mL)
V: nominal capacity of the test solution (mL)
N: number of tablets taken for the test
1.25: peak area for enalapril diketopiperazine relative
to that of enalapril
L: labeled amount of enalapril maleate in the tablet
(mg).
Amount (%) of any other related substances
= C 'V AT 100
N
AS
AT : peak area of any other related substances

C', V, N are defined as the above.
The sum of all related substances including those from

enalaprilat and enalapril diketopiperazine is not greater
than 5.0%.
Enalaprilate standard solution: weigh accurately a portion of Enalapril Maleate RS, dissolve in water to make
about 0.4 mg/mL.
Standard solution: weigh accurately about 20 mg of Enalapril Maleate RS, add 0.5mL of enalaprilate standard solution and 50 mL of buffer solution, then shake well. Add
pH 2.2 phosphate buffer solution to make exactly 100mL.
Related substances standard solution: Pipet exactly 1 mL
of the standard solution, add pH 2.2 phosphate buffer solution to make exactly 100 mL.
leate (C20H28N2O5C4H4O4), add 50 mL of pH 2.2 phosphate buffer solution. Ultrasonicate for 15 minutes, then
shake for 30 minutes, add pH 2.2 phosphate buffer solution to make exactly 100 mL, sonicate for 15 minutes
and filter through a membrane filter. Separately, weigh
accurately about 20 mg of Enalapril Maleate RS, add
0.5mL of enlalaprilat standard solution and dissolve in
50 mL of pH 2.2 phosphate buffer solution, then sonicate,
if necessary, add pH 2.2 phosphate buffer solution to
make exactly 100 mL and use this solution as the standard solution. Perform the test with exactly 50 L each
under Liquid Chromatography according to the following conditions, and determine each peak area, AT and
AS , of the test solution and the standard solution by the
automatic integration method
Amount (mg) of enalapril maleate (C20H28N2O5C4H4O4)
= amount (mg) of Enalapril Maleate RS AT
AS
hydroxypropylsilanized silica gel for liquid chromatography.
Mobile phase: The mixture of pH 2.2 phosphate buffer solution and acetonitrile (75 : 25).
Flow rate: 2mL/minute.
System suitabilit
System performance: Pipet 0.5mL of Enalapril diketopiperazine solution, add the standard solution to
make 25mL. When the procedure is run with 50 L of
this solution, as directed under the above operating conditions, Maleate, Enalaprilat, Enalapril, Enalapril diketopiperazine are eluted in this order with the resolution between their peaks being not less than 2.0.
times with 50 L of the standard solution, as directed under the above operating conditions, the relative standard
deviation of the peak area of enalapril is not more than
2.0%.
Packaging and Storage Preserve in well-colosed containers.
Enflurane
F
F
H

Enalapril Maleate Tablets, weigh accurately a portion of
the powder, equivalent to about 20 mg of enalapril ma-
O
F
and enantiomer
Cl
C3H2ClF5O : 184.49
Description Enflurane is a colorless clear liquid.
Enflurane is slightly soluble in water, miscible with
ethanol or ether.
Enflurane is volatile and not flammable.
Enflurane has no optical activity.
Boiling pointBetween 54 C and 57 C.
Identification (1) Perform the test with 50 L of Enflurane as directed under the Oxygen Flask Combustion
Method to obtain the test solution. The test solution responds to the Qualitative Tests for chloride and fluoride.
(2) Determine the infrared spectra of Enflurane and
Enflurane RS, previously dried, as directed in the liquid
film method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Refractive Index
nD20 : Between 1.302 and 1.304.
Specific Gravity
20
: Between 1.520 and 1.540.
d 20
Purity (1) Acidity and alkalinityTo 60 mL of Enflurane add 60 mL of freshly boiled and cooled water, shake
for 3 minutes to mix, allow to separate completely and
use the water layer as the test solution. To 20 mL of the
test solution add 1 drop of bromcresol purple TS and
0.10 mL of 0.01 mol/L of sodium hydroxide VS: the color of the solution is violet. To 20 mL of the test solution
add 1 drop of bromcresol purple TS and 60 L of 0.01
mol/L hydrochloric acid: VS the color of the solution is
yellow.
(2) ChlorideWeigh 20 g of Enflurane, add 20 mL
of water, shake for 5 minutes, allow to separate completely and use water layer. Pipet 10 mL of the solution
and add 6 mL of dilute nitric acid and water to make 50
(3) Related substancesPerform the test with exactly 5 L of Enflurane as directed under Gas Chromatography according to the following conditions, and determine peak area by the automatic integration method and
calculate the percentage of each peak area reference to
enflurane: the peak area other than enflurane is not more
than 0.10%.
Detector: A thermal conductivity detector.
Column: A fused-silica column about 3 mm in inside
diameter and about 3 m in length, coated the inner surface with 20% diethyleneglycolsuccinic ester for Gas
Chromatography on silica for Gas Chromatography (180
to 250 m ) 5 m in thickness.
about 80 C.
Carrier gas: Helium

time of enflurane is about 3 minutes.
System suitability
Test for required detectability: Pipet 1 mL of Enflurane and add 2-propanol to make 100 mL. Pipet 2 mL
of this solution, add 10 mL of 2-propanol and use this solution as the solution for system suitability. Pipet 1 mL of
this solution and dilute with 2-propanol to exactly 10 mL.
Confirm that the peak area of enflurane obtained with 5
L of this solution is equivalent to 7 to 13% of that with
5 L of the solution for system suitability.
System performance: Mix 5 mL each of Enflurane
and 2-propanol. When the procedure is run with 5 L of
this solution under the above operating conditions, enflurane, 2-propanol are eluted in this order with the resolution between the peaks is not less than 2.0.
the peak area of enflurane is not more than 2.0%.
retention time of enflurane beginning after the solvent
peak.
(4) Residue on evaporationPipet exactly 65 mL of
Enflurane, evaporate on steam bath to dryness and dry
the residue at 105 C for 1 hour: the amount of residue is
not more than 1.0 mg.
direct titration).
Packaging and Storage Preserve in tight container
and store at not more than 30 C.
Enoxacin Hydrate
CH2CH3
HN
N
N
1 1/2 H2O
CO2H
O
C15Hl7FN4O31H2O: 347.34
Enoxacin Hydrate, when dried, contains not less than
98.5% and not more than 101.0% of enoxacin
(C15H17FN4O3: 320.32).
Description Enoxacin Hydrate is a white to pale yellow-brown crystals or crystalline powder.
Enoxacin Hydrate is freely soluble in glacial acetic acid,
slightly soluble in methanol, very slightly soluble in
chloroform, and practically insoluble in water, in ethanol
or in ether.
KP 9 349
Enoxacin Hydrate dissolves in dilute sodium hydroxide
TS.
Enoxacin Hydrate is gradually colored by light.
Identification (1) Place 20 mg of Enoxacin Hydrate
and 50 mg of metallic sodium in a test tube and heat
gradually to ignition with precaution. After cooling, add
0.5 mL of methanol and then 5 mL of water and heat to
boiling. To this solution, add 2 mL of dilute acetic acid
and filter: the filtrate responds to the Qualitative Tests (2)
for fluoride.
(2) Dissolve 50 mg each of Enoxacin Hydrate and
Enoxacin Hydrate RS, in dilute sodium hydroxide TS to
make 100 mL each. To each of 1 mL of the solutions, add
water to make 100 mL each and determine the absorption
spectra as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Determine the infrared spectra of Enoxacin and
Enoxacin RS as directed in the potassium bromide disk
same wavenumbers.
Melting Point
ing).
Between 225 C and 229 C (after dry-
Purity (1) SulfateDissolve 1.0 g of Enoxacin Hydrate in 50 mL of dilute sodium hydroxide TS, shake
with 10 mL of dilute hydrochloric acid and centrifuge.
Filter the supernatant and to 30 mL of the filtrate add water to make 50 mL. Perform the test using this solution as
to 0.50 mL of 0.005 mol/L sulfuric acid VS, add 25 mL
of dilute sodium hydroxide TS, 5 mL of dilute hydrochloric acid and water to make 50 mL (not more than
0.048%).
(2) Heavy metalsProceed with 1.0 g of Enoxacin
(3) ArsenicProceed with 1.0 g of Enoxacin Hydrate according to Method 3 and perform the test (not
more than 2 ppm).
(4) Related substancesDissolve 50 mg Enoxacin
Hydrate in 25 mL of a mixture of chloroform and methanol (7 : 3) and use this solution as the test solution. Pipet
exactly 1 mL of the test solution, add a mixture of chloroform and methanol (7 : 3) to make exactly 200 mL and
chromatography. Develop the plate with a mixture of nbutanol, water and glacial acetic acid (3 : 1 : 1) to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot

Loss on Drying Between 7.0 and 9.0% (1 g, 105 C, 3
hours).
Residue on Ignition Not more than 0.1% (1 g, platinum crucible).
Assay Weigh accurately about 0.3 g of Enoxacin Hydrate, previously dried, dissolve in 30 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 32.032 mg of C15Hl7FN4O3
tight containers.
Ephedrine Hydrochloride
OH
NHCH3
CH2
HCl
C10H15NOHCl: 201.69
Ephedrine Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of ephedrine hydrochloride (C10H15NOHCl).
Description Ephedrine Hydrochloride is a white crystal or crystalline powder.
Ephedrine Hydrochloride is freely soluble in water, soluble in ethanol, slightly soluble in glacial acetic acid,
and practically insoluble in acetic anhydride or acetonitrile.
solutions of Ephedrine Hydrochloride and Ephedrine
Hydrochloride RS, respectively, in water (1 in 2000) as
directed under Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Ephedrine Hydrochloride and Ephedrine Hydrochloride RS as directed
(3) A solution of Ephedrine Hydrochloride (1 in 15)
- 36.0 (after drying, 1 g, water, 20 mL, 100 mm).
Melting Point
pH A solution of Ephedrine Hydrochloride (1 in 20) is

g of Ephedrine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfateDissolve 50 mg of Ephedrine Hydrochloride in 40 mL of water, add 1 mL of dilute hydrochloric
acid and 1 mL of barium chloride TS and allow to stand
for 10 minutes: no turbidity is produced.
(3) Heavy MetalsProceed with 1.0 g of Ephedrine
test. Prepare the control solution with 1.0 mL of Standard
Lead Solution (not more than 10 ppm).
(4) Related SubstanceDissolve 50 mg of Ephedrine Hydrochloride in 50 mL of mobile phase and use
the test solution, add the mobile phase to make exactly
Perform the test with 10 L each of the test and the standard solution as directed under the Liquid Chromatography according to the following condition and calculate
the areas of each peak by the automatic integration method: the total area of all peaks other than principal peak
from the test solution is not greater than that of principal
peak from the standard solution.
about 45 C.
Mobile phase: A mixture of a solution of sodium
lauryl sulfate (1 in 128), acetonitrile and phosphoric acid
(640 : 360 : 1)
time of ephedrine is about 14 minutes.
System suitability
Test for required detectability: Pipet exactly 1 mL
of the standard solution, add mobile phase to make 20
mL. Confirm that the peak area of ephedrine obtained
from 10 L of this solution is equivalent to 4 to 6% of
System performance: Dissolve 1 mg of Ephedrine
Hydrochloride RS and 4 mg of atropine sulfate in 100
mL of diluted methanol (1 in 2). When the procedure is
run with 10 L of this solution as directed under the
above operating conditions, ephedrine and atropine are
under the above operating conditions, the relative standard deviation of the peak areas of ephedrine is not more
than 2.0%.
Time span of measurement: About three times as long as
the retention time of ephedrine after the solvent peak.
hours).
Assay Weigh accurately about 0.4 g of Ephedrine Hydrochloride, previously dried, dissolve in 50 mL of a
by warming. Cool and titrate with 0.1 mol/L perchloric
acid VS (potentiometric titration, endpoint detection method in titrimetry). Perform a blank determination and

Injection
Ephedrine Hydrochloride Injection is an aqueous solution for injection. Ephedrine Hydrochloride Injection
of the labeled amount of ephedrine hydrochloride
(C10H15NOHCl: 201.69).
Method of Preparation Prepare as directed under Injections, with Ephedrine Hydrochloride.
Description Ephedrine Hydrochloride Injection is a
pHThe Between 4.5 and 6.5.
Identification Take a volume of Ephedrine Hydrochloride Injection, equivalent to 50 mg of Ephedrine Hydrochloride according to the labeled amount, add water
to make 100 mL and the determine the absorption spectrum of this solution as directed under the Ultravioletvisible Spectrophotometry: it exhibits maxima between
249 and 253 nm, between 255nm and 259 nm and between 261 nm and 265 nm.
Bacterial Endotoxins Less than 7.5 EU/mg of Ephedrine Hydrochloride.
Foreign Insoluble Matter Test It meets the require-
KP 9 351
ment.
It

Assay Take an exact volume of Ephedrine Hydrochloride Injection, equivalent to about 40 mg of ephedrine
hydrochloride (C10H15NOHCl) according to the labeled
amount, add exactly 10 mL of the internal standard solution and water to make 200 mL and use this solution as
mg of Ephedrine Hydrochloride RS, previously dried at
105 C for 3 hours, add exactly 10 mL of internal standard solution and water to make 200 mL and use this solution as the standard solution. Perform the test with 10
L each of the test and the standard solution as directed
under the Liquid Chromatography according to the following condition and calculate the ratios, QT and QS ,
of the peak area of ephedrine to that of the internal standard of each solution.
Amount (mg) of ephedrine hydrochloride

(C10H5NOHCl ) = amount (mg) of Ephedrine
Hydrochloride RS
QT
QS
Internal standard solutionA solution of etilefrine

and flow rate: Perform as directed in the operating conditions in the Purity (4) under Ephedrine Hydrochloride.
System suitability
with 10 L of the standard solution as directed under the
above operating conditions, the internal standard and
ephedrine are eluted in this order with the resolution between these peaks being not less than 1.5.
times with 10 L of the standard solution as directed under the above operating conditions, the relative standard
deviation of the ratios of the peak area of ephedrine to
that of internal standard is not more than 1.0%.
10% Ephedrine Hydrochloride

Powder
Ephedrine Hydrochloride Powder
Ephedrine Hydrochloride Powder contains not less than

9.3% and not more than 10.7% of ephedrine hydrochloride (C10H15NOHCl: 201.69).
100 g
Starch, Lactose Hydrate
a sufficient quantity or their mixture
Total
1000 g
Identification Take 0.5 g of 10% Ephedrine Hydrochloride Powder, add 100 mL of water, shake for 20 minutes and filter. Determine the absorption spectrum of
the filtrate as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 249 nm and
253 nm, between 255 nm and 259 nm and between 261
nm and 265 nm.
It

Assay Weigh accurately about 0.4 g of 10% Ephedrine
Hydrochloride Powder, add 150 mL of water and extract
with the aid of ultrasonicator for 10 minutes with occasional shaking. Shake more for 10 minutes, add exactly
10 mL of the internal standard solution and water to
make 200 mL, centrifuge and use the supernatant as the
of Ephedrine Hydrochloride RS, previously dried at 105
C for 3 hours, add exactly 10 mL of internal standard
solution and water to make 200 mL and use this solution
each of the test and the standard solution as directed under the Liquid Chromatography according to the following condition and calculate the ratios, QT and QS , of
the peak area of ephedrine to that of the internal standard
of each solution.

Hydrochloride RS
QT
QS

System suitability

Tablets
Ephedrine Hydrochloride Tablets contain not less than
of ephedrine hydrochloride (C10H15NOHCl: 201.69).
Method of Preparation Prepare as directed under Tablets, with Ephedrine Hydrochloride.

Hydrochloride RS

System suitability
Identification Take an amount of powdered Ephedrine

Hydrochloride Tablets, equivalent to 50 mg of Ephedrine
Hydrochloride according to the labeled amount, add 100
mL of water, shake for 20 minutes and filter. Determine
the absorption spectrum of the filtrate as directed under
and 259 nm and between 261 nm and 265 nm.
tablets of Ephedrine Hydrochloride Tablets. Weigh accurately an amount of powder, equivalent to about 40 mg
of Ephedrine Hydrochloride, add 150 mL of water and
extract with the aid of ultrasonicator for 10 minutes with
occasional shaking. Shake more for 10 minutes, add exactly 10 mL of the internal standard solution and water to
make 200 mL, centrifuge and use the supernatant as the
of Ephedrine Hydrochloride RS, previously dried at 105
C for 3 hours, add exactly 10 mL of internal standard
solution and water to make 200 mL and use this solution
each of the test and the standard solution as directed under the Liquid Chromatography according to the following condition and calculate the ratios, QT and QS , of
the peak area of ephedrine to that of the internal standard
of each solution.
QT
QS
Epinephrine
OH
HO
CH2NHCH3
H
HO
Adrenaline
Epirenamine
C9H13NO3: 183.20
Epinephrine, when dried, contains not less than 98.0%

and not more than 101.0% of epinephrine (C9H13NO3:
183.20).
Description Epinephrine is a white to grayish white,
crystalline powder and odorless.
Epinephrine is freely soluble in glacial acetic acid, very
slightly soluble in water, and practically insoluble in methanol, ethanol or ether.
Epinephrine dissolves in dilute hydrochloric acid.
Epinephrine gradually changes to brown in color by air
and by light.
Identification (1) Dissolve 10 mg of Epinephrine in 10
mL of diluted acetic acid (1 in 500) and use this solution
as the test solution. Take 1 mL of the test solution, add 4
mL of water and 1 drop of ferric chloride TS: a deep
green color is observed and it gradually changes to red.
(2) Place 1 mL each of the test solution obtained in
(1) in test tubes, A and B. Add 10 mL of potassium biph-
KP 9 353
thalate buffer solution, pH 3.5, in A and add 10 mL of
phosphate buffer solution, pH 6.5, in B. To each of the
test tubes, add 1 mL of iodine TS, allow to stand for 5
minutes and add 2 mL each of sodium thiosulfate TS: a
red color is observed in test tube A and a deep red color
is observed in test tube B.
Adrenaline Hydrochloride Injection

- 53.5 (after drying, 1 g, 1 mol/L hydrochloric acid TS,
25 mL, 100 mm).
Method of Preparation Dissolve Epinephrine in diluted hydrochloric acid (9 in 10000) and prepare as directed under Injections.

g of Epinephrine in 10 mL of dilute hydrochloric acid:
the solution is clear and has no more color than Color
Matching Fluid A.
(2) AdrenaloneDissolve 50 mg of Epinephrine in
0.05 mol/L hydrochloric acid TS to make exactly 25 mL
and determine the absorbance of this solution at 310 nm
as directed under the Ultraviolet-visible Spectrophotometry: it is not more than 0.40.
(3) NorepinephrineDissolve 10.0 mg of Epinephrine in 2.0 mL of a tartaric acid solution (1 in 200). Pipet
exactly 1 mL of the solution, add 3.0 mL of pyridine, add
1.0 mL of freshly prepared sodium naphthoquinone sulfonate TS and allow to stand in a dark place for 30 minutes. Take this solution, add 5.0 mL of pyridine containing 50 mg of Ascorbic Acid: the solution has no more
color than the following control solution.
Description Epinephrine Injection is a colorless, clear

liquid.
Epinephrine Injection changes gradually to pale red and
then to brown on exposure to air and light.
Control solutionDissolve 2.0 mg of Norepinephrine Bitartrate RS and 90 mg of Epinephrine Bitartrate

RS in methanol to make exactly 10 mL. Pipet exactly 1
mL of this solution and proceed in the same manner.
Assay Weigh accurately about 0.3 g of Epinephrine,

= 18.321 mg of C9H13NO3
Packaging and Storage Preserve in light-resistant, under nitrogen atmosphere and in a cold place, tight containers.
Epinephrine Injection
Epinephrine Hydrochloride Injection
Epirenamine Hydrochloride Injection
Epinephrine Injection is an aqueous solution for injection.

Epinephrine Injection contains not less than 0.085 w/v %
and not more than 0.115 w/v % of epinephrine
(C9H13NO3: 183.20).
Identification (1) Take 1 mL of Epinephrine Injection,

add 4 mL of water and 1 drop of ferric chloride TS: a
deep green color is observed and it gradually changes to
red.
(2) Place 1 mL each of Epinephrine Injection in test
tubes, A and B, and proceed as directed in the Identification (2) under Epinephrine.
It

Assay Pipet exactly 30 mL of Epinephrine Injection into a separatory funnel, add 25 mL of carbon tetrachloride,
shake vigorously for 1 minute, allow the liquids to separate and discard the carbon tetrachloride layer. Repeat
this procedure 3 times. Rinse the stopper and mouth of
the separatory funnel, with a small amount of water. Add
0.2 mL of starch TS, then while shaking the separatory
funnel, add iodine TS dropwise until a persistent blue
color is observed and immediately add sodium thiosulfate TS to discharge the blue color. Add 2.1 g of sodium
bicarbonate to the liquid in the separatory funnel, preventing it from coming in contact with the mouth of the
separatory funnel and shake until most of the sodium bicarbonate dissolves. Rapidly inject 1.0 mL of acetic anhydride into the contents of the separatory funnel. Immediately stopper the separatory funnel loosely and allow to
stand until the evolution of gas ceases. Shake vigorously,
allow to stand for 5 minutes, extract with six 25 mL volumes of chloroform and filter each chloroform extract
through a pledget of absorbent cotton. Evaporate the
combined chloroform extracts in a water-bath in a current of air to 3 mL, completely transfer this residue by
means of small portions of chloroform to a tared beaker

and heat again to evaporate to dryness. Dry the residue at
105 C for 30 minutes, cool in a desiccator (silica gel)
and accurately measure the weight, W (mg), of the dried
residue. Dissolve in chloroform to make exactly 5 mL
and determine the specific optical rotation D using a
100-mm cell as directed under the optical Rotation Determination .
Amount (mg) of Epinephrine (C9H13NO3)
0 .5 D
= 0 .5923 W (0.5 +
)
93

hermetic containers and colored containers may be used.
Epirizole
CH 3
H 3C
N
N
N
OCH 3
Mepirizole
OCH 3
C11H14N4O2: 234.25
Epirizole, when dried, contains not less than 99.0% and

not more than 101.0% of epirizole (C11H14N4O2).
Description Epirizole is a white crystal or crystalline
powder. Epirizole is odorless and has a bitter taste.
Epirizole is very soluble in methanol or in glacial acetic
acid, freely soluble in ethanol, and sparingly soluble in
water or in ether.
Epirizole dissolves in dilute hydrochloric acid or in sulfuric acid.
The pH of a solution of Epirizole (1 in 100) is between
6.0 and 7.0.
Identification (1) Take 0.1 g of Epirizole, add 0.1 g of
vanillin, 5 mL of water and 2 mL of sulfuric acid and
mix with shaking for a while: a yellow precipitate is produced.
(2) Dissolve 0.1 g of Epirizole in 10 mL of water and
add 10 mL of picric acid TS: a yellow precipitate is produced. Collect the precipitate by filtration, wash with 50
mL of water and dry at 105 C for 1 hour: it melts between 163 C and 169 C.
Epirizole and Epirizole RS, respectively, in 0.1 mol/L
hydrochloric acid VS (1 in 200000) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit
Melting Point

0.20 g of Epirizole in 20 mL of water: the solution is

(2) ChlorideAdd 0.5 g of Epirizole to a ground
mixture of 0.7 g of potassium nitrate and 1.2 g of anhydrous sodium carbonate, mix well, transfer little by little to a platinum crucible, previously heated, and heat until the reaction is completed. After cooling, add 15 mL of
dilute sulfuric acid and 5 mL of water to the residue, boil
for 5 minutes, filter, wash the insoluble matter with 10
mL of water and add 6 mL of dilute nitric acid and water
to the combined filtrate and washings to make 50 mL.
Perform the test with this solution as the test solution.
Prepare the control solution as follows: When the procedure is run with the same quantities of the same reagents
as directed for the preparation of the test solution and
add 0.25 mL of 0.01 mol/L hydrochloric acid VS and water to make 50 mL (not more than 0.018%).
(3) Heavy metalsProceed with 2.0 g of Epirizole
(4) ArsenicProceed with 1.0 g of Epirizole according to Method 3 and perform the test (not more than 2
ppm).
(5) Related substancesDissolve 1.0 g of Epirizole
in 10 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution and add
methanol to make exactly 50 mL. Pipet exactly 1 mL of
this solution, add methanol to make exactly 10 mL and
plate of silica gel with fluorescent indicator for thin-layor
isopropyl ether, ethanol and water (23 : 10 : 2) to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot
more intense than that from the standard solution. Place
this plate in a chamber filled with iodine vapor: any spot
test with 0.10 g of Epirizole: the solution has no more
hours).
Assay Weigh accurately about 0.5 g of Epirizole, previously dried, dissolve in 40 mL of glacial acetic acid
2 drops of methylrosaniline chloride TS) until the color
of the solution changes from purple through blue-green
to green. Perform a blank determination and make any
KP 9 355
= 23.426 mg of C11H14N4O2
tween 4.0 and 5.5.

1%
Epirubicin Hydrochloride
OH
OH
OH
OH
OH
H3 C
H3C
HCl
NH2
C27H29NO11HCl: 579.98
Epirubicin Hydrochloride is the hydrochloride of a derivative of daunorubicin.
Epirubicin Hydrochloride contains not less than 900 g
(potency) of per mg of epirubicin hydrochloride
(C27H29NO11 HCl), calculated on the anhydrous basis
and corrected by the amount of the residual solvent.
Description Epirubicin Hydrochloride is a pale yellow
or red-brown powder.
Epirubicin Hydrochloride is soluble in water or in methanol, slightly soluble in ethanol, and practically insoluble in ether, in chloroform, or in acetonitrile.
Epirubicin Hydrochloride is hygroscopic.
Identification (1) Weigh 1 - 2 mg of Epirubicin Hydrochloride, dissolve in 5 mL of 1 mol/L sodium hydroxide: a blue-purple color develops.
(2) Weigh 5 mg of Epirubicin Hydrochloride, dissolve in 5 mL of water, add 1 mL of nitric acid and 2 to 3
drops of silver nitrate TS and mix with shaking: the solution turns to be turbid.
(3) Weigh 15 mg of Epirubicin Hydrochloride, dissolve in methanol to make 1000 mL, and use this solution as the test solution. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible
Spectrophotometry, it exhibits maxima between 232 nm
and 236 nm, and between 250 nm and 254 nm, and between 286 nm and 290 nm, and between 477 nm and 481
nm, and between 493 nm and 497 nm, and between 527
nm and 531 nm.
D : +310 ~ +340 (10
mg calculated on the anhydrous basis and corrected by
the amount of the residual solvent, methanol, 20 mL, 100
mm).
of Epirubicin Hydrochloride in 10 mL of water is be-
Absorbance E1 cm (495 nm): 200 ~ 230 (15 mg calculated on the anhydrous basis and corrected by the amount
of the residual solvent, methanol, 1000 mL).
Purity Residual solventsWeigh accurately about 50
mg of Epirubicin Hydrochloride, dissolve in water to
make exactly 5 mL, and use this solution as the test solution. Separately, weigh accurately about 1.0 g of npropanol, add water to make exactly 100 mL, pipet exactly 1 mL of this solution, add water to make exactly
100 mL, and use this solution as the n-propanol standard
solution. Separately, weigh accurately about 1 g of acetone, add water to make exactly 100 mL, pipet exactly 1
mL of this solution, add water to make exactly 100 mL,
and use this solution as the acetone standard solution.
the standard solutions as directed under the Gas Chromatography according to the following operating conditions,
and determine the peak heights of n-propanol and acetone in the test solution, H1 and H2, and in the standard
solutions, HS1 and HS2 (the total amount of n-propanol
and acetone: not more than 5.0 %).
Amount [%] of n-propanol in 1 g of Epirubicin Hydrochloride

= Amount [g] of n - propanol taken H1 0.0005
H S1
100
Amount (g) of Epirubicin Hydrochlor ide
Amount [%] of acetone in 1 g of Epirubicin Hydrochloride

= Amount [g] of acetone taken H 2 0.0005
HS2
1
100
Amount (g) of Epirubicin Hydrochlor ide
Detector: A flame-ionization detector
Column: A glass column, about 3.2 mm in inside diameter and about 2 m in length, packed with porous polymerbis (50/80 mesh).
Injector temperature: A constant temperature at about
170 C
Column temperature: A constant temperature at about
120 C
time of n-propanol is about 12 minutes.
Sterility Test It meets the requirement, When Epirubicin Hydrochloride is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Epirubicin Hydrochloride is used in a sterile preparation,. Weigh

an appropriate amount of Epirubicin Hydrochloride, dissolve in water, make the solution so that each mL contains 2.0 mg, and use the solution as the test solution.
The amount of injection is 1.0 mL of the test solution per
kg of body weight of rabbit.
tios of the peak area of epirubicin to that of the internal

standard is not more than 1.0 %.
Histamine It meets the requirement, when Epirubicin

Hydrochloride is used in a sterile preparation. Weigh an
appropriate amount of Epirubicin Hydrochloride, dissolve in water to make the solution so that each mL contains 15 mg, and use the solution as the test solution. Use
0.5 mL of this solution for the test.
Ergocalciferol
H
H3C

direct titration).
Assay Weigh accurately about 10 mg each of Epirubicin Hydrochloride and Epirubicin Hydrochloride RS, add
the internal standard solution to make exactly 10 mL,
and use these solutions as the test solution and the standard solution, respectively. Perform the test with 5 L of
the following operating conditions, and determine the ratios, QT and QS, of the peak area of epirubicin hydrochloride to that of the internal standard.
Amount [g (potency)] of epirubicin hydrochloride

(C27H29NO11HCl)
= amount [g (potency)] of Epirubicin Hydrochloride RS
QT
QS
Internal standard solutionWeigh 1 g of sodium 2naphthalene sulfonate, and dissolve in the mixture of water and acetonitrile (60:31) to make 500 mL.
Mobile phase: Adjust the pH of a mixture of water
and acetonitrile (69:31) to 2.0 with phosphoric acid
time of epirubicin hydrochloride is about 10minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, the internal standard and epirubicin hydrochloride are eluted in this order with the resolution
between these peaks being not less than 8.0.
times with 5 L of the standard solution under the operating conditions, the relative standard deviation of the ra-
CH3
H3C
CH3
H
CH3
CH2
HO
H
Calciferol
Vitamin D2
C28H44O: 396.65
Ergocalciferol contains not less than 97.0% and not more

than 103.0% of ergocalciferol (C28H44O).
Description Ergocalciferol is a white crystal, is odorless or has a faint, characteristic odor.
Ergocalciferol is freely soluble in ethanol, ether, or chloroform, sparingly soluble in isooctane and practically insoluble in water.
Ergocalciferol is affected colored by air and by light.
Melting pointBetween 115 C and 118 C. Transfer
Ergocalciferol to a capillary tube and dry for 3 hours in a
desiccator (at a pressure not exceeding 2.67 kPa). Immeadiately fireseal the capillary tube, put it in a bath fluid, previously heated to a temperature about 10 C below
the expected melting point and heat at a rate of rise of
about 3 C per minute and read the melting point.
Identification (1) Dissolve 0.5 mg of Ergocalciferol in
5 mL of chloroform, add 0.3 mL of acetic anhydride and
0.1 mL of sulfuric acid and shake: a red color is observed
and rapidly changes through purple and blue to green.
(2) Determine the infrared spectra of Ergocalciferol
and Ergocalciferol RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry,
respectively: both spectra exhibit similar intensities of
%
Absorbance E11cm
(10 mg, ethanol, 1000 mL).

+ 107 (0.3 g, ethanol, 20 mL, 100 mm). Prepare the solution of Ergocalciferol within 30 minutes after the con-
KP 9 357
tainer has been opened and determine the rotation within
30 minutes after the solution has been prepared.
Purity ErgostrerolDissolve 10 mg of Ergocalciferol
in 2.0 mL of diluted ethanol (9 in 10), add allow 20 mg
of digitonin in 2.0 mL of ethanol (9 in 10) and allow the
mixture to stand for 18 hours: no precipitate is produced.
Assay Weigh accurately about 30 mg of Ergocalciferol
and Ergocalciferol RS and dissolve each in isooctane to
make exactly 50 mL. Pipet exactly 10 mL each of these
solutions, add exactly 3 mL each of the internal standard
solution, then add the mobile phase to make exactly 50
to 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of the peak area of Ergocalciferol to
that of the internal standard, respectively. Perform the
procedure rapidly avoiding contact with air or other oxidizing agents and using light-resistant containers.
being not less than 0.7 and that between ergocalciferol

and tachysterol2 being not less than 1.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of ergocalciferol to that
hermetic containers (in a cold place after displacement
air with nitrogen).
Ergometrine Maleate
O
Internal standard solutionA solution of dimethylphthalate in isooctane (1 in 100)

a silica gel for liquid chromatography (5 m to 10 m in
particle diameter).
about 20 C.
Mobile phase: A mixture of hexane and namylalcohol (997 : 3).
time of Ergocalciferol is about 25 minutes.
System Suitability
System performance: Dissolve 15 mg of Ergocalciferol RS in 25 mL of isooctane. Transfer this solution
to a flask, heat in an oil-bath under a reflux condenser for
2 hours and cool immediately to room temperature.
Transfer the solution to a quartz test tube and irradiate
with a short-wave lamp (main wavelength: 254 nm) and
a long-wave lamp (main wavelength: 365 nm) for 3
hours. Take 10 mL of this solution, add the mobile phase
to make 50 mL. When the procedure is run with 10 L of
this solution, as directed under the above operating conditions. the ratios of the retention time of previtamin D2,
trans-vitamin D2 and tachysterol2 to that of ergoclaciferol
are about 0.5, about 0.6 and about 1.1, respectively with
resolution between previtamin D2 and trans-vitamin D2
C
N
H
CH3
CO2H
H
N
H
Amount (mg) of Ergocalciferol (C28H44O)

Q
= amount (mg) of Ergocalciferol RS T
QS
CH2OH
H
H
CH3
C
H
CO2H
HN
Ergonovine Maleate
C19H23N3O2C4H4O4: 441.48
Ergometrine Maleate, when dried, contains not less than

98.0% and not more than 101.0% of ergometrine maleate
(C19H23N3O2C4H4O4).
Description Ergometrine Maleate is a white to pale
yellow, crystalline powder, and is odorless.
Ergometrine Maleate is sparingly soluble in water,
slightly soluble in methanol or in ethanol, and practically
insoluble in ether.
Ergometrine Maleate gradually changes to yellow in color on exposure to light.
Identification (1) Prepare a solution of Ergometrine
Maleate (1 in 50): the solution shows a blue fluorescence.
(2) Dissolve 1 mg of Ergometrine Maleate in 5 mL of
water. Take 1 mL of this solution, add 2 mL of pdimethylaminobenzaldehyde-ferric chloride TS, shake,
and allow to stand for 5 to 10 minutes: a deep blue color
is observed.
(3) Take 5 mL of a solution of Ergometrine Maleate
(1 in 500), add 1 drop of potassium permanganate TS:
the red color of the solution disappears immediately.
D : Between +48 and
+57 (after drying, 0.25 g, water, 25 mL, 100 mm).
pH Dissolve 0.10 g of Ergometrine Maleate in 10 mL
of water. The pH of this solution is between 3.0 and 5.0.
Purity
(1) Clarity and color of solutionDissolve

0.10 g of Ergometrine Maleate in 10 mL of water: the solution is clear and colorless to light yellow.
(2) Ergotamine and ergotoxineTake 20 mg of Ergometrine Maleate, add 2 mL of sodium hydroxide solution (1 in 10), and heat to boiling: the gas evolved does
not change moistened red litmus paper to blue.
(3) Related substancesDissolve 5.0 mg each of
Ergometrine Maleate and Ergometrine Maleate RS in exactly 1 mL of methanol, and use these solutions as the
test solution and the standard solution, respectively. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution and the standard solution on a plate, prepared with silica gel for thin-layer
chromatography and dilute sodium hydroxide TS. Develop the plate with a mixture of chloroform and methanol (4 : 1) to a distance of about 10 cm, and air-dry the
plate. Spray evenly p-dimethylaminobenzaldehyde TS on
the plate: the spots obtained from the test solution and
the standard solution show a red-purple color and the
same Rf value, and any spot from the test solution other
than the spot from the standard solution does not appear.
Loss on Drying
4 hours).
Not more than 2.0% (0.2 g, silica gel,
Assay Weigh accurately about 10 mg each of Ergometrine Maleate and Ergometrine Maleate RS, previously
dried in a desiccator (silica gel) for 4 hours, dissolve separately in water to make exactly 250 mL, and use these
Pipet exactly 2 mL each of the solutions and put separately into a brown glass-stoppered tube. To each tube
add 4 mL of p-dimethylamino-benzaldehyde-ferric chloride TS, exactly measured, while cooling in an ice-bath,
then warm at 45 C for 10 minutes. Allow to stand at
room temperature for 20 minutes, and perform the test
with these solutions as directed under the Ultravioletvisible Spectrophotometry using a solution, prepared
with 2 mL of water in the same manner, as the blank. Determine the absorbances, AT and AS , of the subsequent solution of the test solution and the standard solution at 550 nm, respectively.
Amount (mg) of ergometrine maleate

(C19H23N3O2C4H4O4) = amount (mg) of Ergometrine
Maleate RS
tight containers.
AT
AS
Ergometrine Maleate Injection

Ergonovine Maleate Injection
Ergometrine Maleate Injection is an aqueous solution for
injection. Ergometrine Maleate Injection contains not
amount of ergometrine maleate (C19H23N3O2C4H4O4:
441.48).
Method of Preparation Prepare as directed under Injections, with Ergometrine Maleate.
Description Ergometrine Maleate Injection is a clear,
colorless to pale yellow liquid.
Identification (1) Measure a volume of Ergometrine
Maleate Injection, equivalent to 3 mg of Ergometrine
Maleate according to the labeled amount, if necessary,
dilute with water or evaporate on a water-bath to make
15 mL and use this solution as the test solution: the test
solution shows a blue fluorescence.
(2) Add 1 mL of ammonia TS to 1 mL of the test solution obtained in (1) and extract with 20 mL of ether. To
the ether extract, add 1 mL of dilute sulfuric acid, shake
and warm to remove ether on a water-bath. Cool, add 2
mL of p-dimethylaminobenzaldehyde-ferric chloride TS
to the residue obtained and allow to stand for 5 to 10 minutes: a deep blue color is observed.
(3) Add 1 drop of potassium permanganate TS to 5
mL of the test solution obtained in (1): a red color disappears immediately.
It

Assay Transfer an exactly measured volume of Ergometrine Maleate Injection, equivalent to about 2 mg of
ergometrine maleate (C19H23N3O2C4H4O4) and add sodium chloride in a ratio of 0.3 g to 1 mL of the solution.
To this mixture, add 20 mL of ether and 2 mL of ammonia TS, shake and extract. Further, extract with three 15
mL volumes of ether, combine all the extracts, add 5 g of
anhydrous sodium sulfate, filter through a pledget of absorbent cotton and wash with three 5 mL volumes of ether. Add the washings to the filtrate, shake with 5 mL of
dilute sulfuric acid, evaporate the ether by warming in a
current of nitrogen, add water to the remaining solution
KP 9 359
solution. Separately, weigh accurately about 2 mg of Ergometrine Maleate RS, previously dried in a desiccator
(silica gel) for 4 hours, dissolve in water to make exactly
50 mL and use this solution as the standard solution. Pipet exactly 2 mL each of the test solution and the standard solution, and proceed as directed in the Assay under
Ergometrine Maleate.
while cooing in an ice-bath, after shaking and allow to

stand for 1 hour at room temperature. Perform the test
with these solutions as directed under the Ultravioletvisible Spectrophotometry using a solution, prepared
with 4 mL of water in the same manner, as the blank. Determine the absorbances, AT and AS , of the subsequent solutions of the test solution and the standard solution at 550 nm, respectively.

(C19H23N3O2C4H4O4)

(C19H23N3O2C4H4O4)
= amount (mg) of Ergometrine Maleate RS
AT
AS

hermetic containers at a cool place and colored containers may be used.
Ergometrine Maleate Tablets

Ergonovine Maleate Tablets
Ergometrine Maleate Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of ergometrine maleate (C19H23N3O2C4H4O4: 441.48).
Method of Preparation Prepare as directed under Tablets, with Ergometrine Maleate.
Identification Powder Ergometrine Maleate Tablets,
weigh a portion of the powder equivalent to 3 mg of Ergometrine Maleate according to the labeled amount, add
15 mL of warm water, shake and filter: the filtrate shows
a blue fluorescence. Perform the test with this solution as
directed in the Identification (2) and (3) under Ergometrine Maleate.
= amount (mg) of Ergometrine Maleate RS AT V

AS
100

Ergometrine Maleate Tablets. Weigh accurately a portion
of the powder, equivalent to about 2 mg of ergometrine
maleate (C19H23N3O2C4H4O4), transfer to a glass filter
(G4), add 10 mL of a solution of tartaric acid (1 in 100)
and filter with thorough shaking. Repeat the procedure
three times, combine the filtrates, add a solution of tartaric acid (1 in 100) to make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately
about 2 mg of Ergometrine Maleate RS, previously dried
in a desiccator (silica gel) for 4 hours, dissolve in a solution of tartaric acid (1 in 100) to make exactly 50 mL and
use this solution as the standard solution. Pipet exactly 2
mL each of the test solution and the standard solution
and proceed as directed in the Assay under Ergometrine
Maleate.

(C19H23N3O2C4H4O4) = amount (mg) of Ergometrine
Maleate RS
AT
AS

when the Content Uniformity Test is performed according to the following method.
Transfer 1 tablet of Ergometrine Maleate Tablets to a
glass-stoppered centrifuge tube and add exactly V mL of
a solution of tartaric acid (1 in 100) to make of a solution
containing about 40 g of ergometrine maleate
(C19H23N3O2C4H4O4) per mL. Stopper the tube, shake
for 30 minutes vigorously, centrifuge and use the supernatant as the test solution. Separately, weigh accurately
about 4 mg of Ergometrine Maleate RS, previously dried
in a desiccator (silica gel) for 4 hours, dissolve in water
standard solution. Pipet exactly 4 mL each of the test solution and the standard solution, put separately into
brown glass-stoppered test tubes, add exactly 8 mL each
of p-dimethylamino-benzaldehyde-ferric chloride TS
Ergotamine Tartrate
OH
CH3
O
H
CONH
N
H
N
O
H
CH(OH)CO2H
CH2
CH3
CH(OH)CO2H
HN
(C33H35N5O5)2C4H6O6: 1313.41
Ergotamine Tartrate contains not less than 98.0% and not

more than 101.0% of ergotamine tartrate [(C33H35N5O5)2
C4H6O6], calculated on the dried basis.
Description Ergotamine Tartrate is a colorless crystals,
or a white to pale yellowish white or grayish white, crystalline powder.
Ergotamine Tartrate is slightly soluble in water or ethanol.
Identification (1) Dissolve 1 mg of Ergotamine Tartrate in 10 mL of a mixture of glacial acetic acid and
ethyl acetate (1 : 1). Pipet 0.5 mL of this solution, add
slowly 0.5 mL of sulfuric acid, with shaking in cold water and allow to stand: a purple color develops. Add 0.1
mL of diluted ferric chloride TS (1 in 12) to this solution:
the color of the solution changes to blue or to blue-purple.
(2) Dissolve 1 mg of Ergotamine Tartrate in 5 mL of
a solution of tartaric acid (1 in 100). To 1 mL of this solution, add 2 mL of p-dimethylaminobenzaldehyde-ferric
chloride TS and shake: a blue color develops.
[ ]20
D
Specific Optical Rotation Ergotamine base

:
Between -155 and -165. Dissolve 0.35 g of Ergotamine
Tartrate in 25 mL of a solution of tartaric acid (1 in 100),
add 0.5 g of sodium bicarbonate, shake gently and sufficiently and extract with four 10 mL volumes of ethanolfree chloroform. Filter the extracts successively through
a small filter paper, moistened with ethanol-free chloroform, into a 50-mL volumetric flask. Allow the flask to
stand in a water-bath at 20 o C for 10 minutes and add
ethanol-free chloroform (20 o C ) to make 50 mL and determine the optical rotation in a 100-mm cell. Separately,
pipet exactly 25 mL of this solution, evaporate to dryness
under reduced pressure at a temperature not higher than
45 o C , dissolve the residue in 25 mL of glacial acetic acid and titrate with 0.05 mol/L perchloric acid VS (indicator: 1 drop of methylrosaniline chloride TS). Perform a
Calculate the specific optical rotation of the ergotamine
base from the consumed volume of 0.05 mol/L perchloric acid VS and the optical rotation.

= 29.084 mg of C33H35N5O5
Purity Related substancesPerform this procedure
without exposure to daylight, using light-resistant vessels.
Weigh 40 mg of Ergotamine Tartrate, add exactly 10 mL
of a solution of tartaric acid in diluted methanol (1 in 2)
(1 in 1000), dissolve by thorough shaking and use this
test solution, add a solution of tartaric acid in diluted methanol (1 in 2) (1 in 1000) to make exactly 50 mL and
test with the test solution and the standard solution as directed under the Thin-layer chromatography. Spot 10 L
plate of silica gel for Thin-layer chromatography. Develop the plate with a mixture of chloroform and methanol
Spray evenly p-dimethylamino-benzaldehyde TS on the
plate: any spot other than the principal spot from the test
60 C, 4 hours).
Assay Weigh accurately about 0.2 g of Ergotamine Tartrate, dissolve in 15 mL of a mixture of glacial acetic acid and acetic anhydride (50 : 3) and titrate with 0.05
mol/L perchloric acid VS (indicator: 1 drop of methylrosaniline chloride TS). Perform a blank determination and

= 32.836 mg of (C33H35N5O5)2C4H6O6
tight containers and almost well-filled, or under nitrogen
atmosphere. Store at not exceeding 5 C.
Ergotamine Tartrate Injection

Ergotamine Tartrate Injection is an aqueous solution for
injection. Total alkaloid is 0.45 to 0.55 mg per mL, ergotamine tartrate [(C33H35N5O5)2C4H6O6: 1313.41] is
52.0% to 74.0% of total alkaloid content and Ergotamininine Tartrate is not more than 45.0% of total alkaloid
content.
Method of Preparation Prepare as directed under Injections, with Ergotamine Tartrate.
Description Ergotamine Tartrate Injection is a clear,
colorless liquid.
Identification (1) Evaporate a weighed volume of Ergotamine Tartrate Injection, equivalent to 0.1 mg of Ergotamine Tartrate according to the labeled amount, on a
steam-bath to dryness. Dissolve the residue in 1 mL of a
mixture of glacial acetic acid and ethyl acetate (1 : 1).
Proceed with 0.5 mL of this solution under Identification
(1) of Ergotamine Tartrate.
(2) Weigh a volume of Ergotamine Tartrate Injection,
equivalent to 0.2 mg of Ergotamine Tartrate according to
the labeled amount, add 2 mL of p-dimethylamino benzaldehyde-ferric chloride reagent: it turns blue.
pH

Bacterial Endotoxins Less than 357.0 EU/mg of ergo-
KP 9 361
tamine tartrate.
It

Assay Take accurately a volume of Ergotamine Tartrate
Injection in a beaker, equivalent to about 5 mg of ergotamine tartrate [(C33H35N5O5)2C4H6O6] according to the
labeled amount, add 5 mL of chloroform saturated with
water and a portion of sodium bicarbonate approximately
equivalent in mass to one tenth that of the portion of Ergotamine Tartrate Injection taken and mix well. Add sufficient chromatographic siliceous earth (about 1 g for
each mL of the Ergotamine Tartrate Injection taken plus
3 g in addition). Pack the mixture in a chromatographic
column, 2.5 cm in inner diameter and 30 cm in length
and this column as the 1st column. Rinse the sides of the
beaker with 2 mL of chloroform saturated with water and
transfer it to the column. Add sufficient amount of siliceous earth to the rinsed solution and transfer it to the
above 1st column. Separately, prepare column using a
mixture of 9 g of the siliceous earth with 7 mL of citric
acid solution (1 in 4) in the 2nd chromatographic column.
Place a mixture of 2 g of the siliceous earth and 2 mL of
water on top of the 2nd column. Insert pledge of glass
wool and mount the tube containing the spectrum so that
elute from the 1st column will drain into the 2nd column.
Add a total of 90 mL of chloroform saturated with water
to the 1st column and receive elute from the 2nd column
in a 200-mL volumetric flask. Rinse the tip of the 1st column with chloroform saturated with water, add chloroform saturated with water to a volume and use this solution as the Ergotaminine test solution. Extrude the adsorbent from the column by means of slight air pressure into
a 600-mL beaker containing 10 g of sodium bicarbonate
and mix. Cautiously add 50 mL of water, with continuous stirring and wash the mixture into a 250-mL separatory funnel and extract the ergotamine with four 15 mL
volumes of chloroform saturated with water. Pass the extracts through a glass wool filter, combining them in a
volumetric flask, wash the filter and dilute with chloroform saturated with water to make 100 mL and use this
solution as the ergotamine test solution. Separately, pipet
a volume of Ergotamine Tartrate Injection, equivalent to
about 2.5 mg of Ergotamine Tartrate, into a 50 mL volumetric flask, add 25 mL of ethanol, then add tartaric acid
solution (1 in 100) to make 50 mL and use this solution
as the total alkaloid test solution. Separately, weigh accurately about 10 mg of the Ergotamine Tartrate RS and
dissolve in 50 mL dilute ethanol solution with warm if
necessary. Add water until 1 mL containing 50 g of Ergotamine Tartrate and use this sodium as the standard solution. Pipet 20 mL of the Ergotamine test solution and
10 mL of Ergotaminine test solution into separate, small

conical flask. To the dried residue of the each solutions,
add 5.0 mL of a mixture of ethanol andtartaric acid solution (1 in 100) (1 : 1) and dissolve. Pipet 5.0 mL each of
the total alkaloid test solution and the standard solution
into conical flasks separately. Place 4 each flasks in an
ice-bath and swirl continuously while adding, dropwise,
10.0 mL of p-dimethyl-aminobenzaldehyde TS. Allow to
stand at room temperature for not less than 90 minutes
and not more than 2 hours. Determine the absorbances of
the four solutions at the wavelength of a maximum absorbance at about 545 nm, with a suitable spectrophotometer, against a reagent blank.
Amount (mg) of the total alkaloid = 0 .05 C
AU
AS
Amount (%) of ergotamine tartrate

[(C33H35N5O5)2C4H6O6] = 50 A '
AU
Amount (%) of ergotaminine tartrate

[(C33H35N5O5)2C4H6O6] = 50 A"
AU
C: Concentration of Ergotamine Tartrate in the standard solution (g/mL),

AS : Absorbance of the standard solution,
AU : Absorbance of the total alkaloid test solution,
A': Absorbance of the Ergotamine test solution
A": Absorbance of the Ergotaminine test solution.
Ergotamine Tartrate Tablets

Ergotamine Tartrate Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of ergotamine tartrate [(C33H35N5O5)2C4H6O6: 1313.41].
Method of Preparation Prepare as directed under Tablets, with Ergotamine Tartrate.
Identification Weigh accurately a portion of Ergotamine Tartrate Tablets, previously dried, equivalent to
about 5 mg of labeled amount and make powder.. Add 10
mL of hexane and shake and mix for a while. Place and
delete hexane extracts and add 10 mL of chloroform saturated with strong ammonia water and shake and mix
for a while, filter. Evaporate the filtrate in water bath.
Dissolve the residue in 8 ml of a mixture of glacial acetic
acid and ethyl acetate (1 : 1), pipet 1 mL of this solution.
Shake and mix in ice bath and at the same time drop 1
mL of sulfuric acid: the solution is violet. Add 0.1 mL of
diluted ferric chloride TS (1 in 2) in this solution: the

color is blue and blue-violet.
and water (55 : 45).
Disintegration Test Disintegrate in 5 minutes for Tablets intended for sublingual use.
(3 m to10 m in particle diameter).
Mobile phase: A mixture of acetonitrile: 0.01mol/L
potassium dihydrogenphosphate (55 : 45).
System suitability
above operating conditions, the symmetry factor of ergotamine is not more than 2.0 and the resolution between
peaks of ergotamine and internal standard is not less than
3.0.
above operating conditions, the relative standard deviation of ratios of the peak areas is not more than 2.0%.
Dissolution Test This test is not applied to Sublingual

Tablets. Take 1 tablet of Ergotamine Tartrate Tablet and
perform the test at 75 revolutions per minute as directed
in the Method 2 under Dissolution Test using 1000 mL of
a solution of tartaric acid (1 in 100) as the dissolution solution. After 30 minutes from the start of the test, take 20
mL or more of the dissolved solution, filter and use the
filtrate as the test solution. Separately, weigh accurately
adequate amount of Ergotamine Tartrate RS, dissolve in
dissolution solution to make a solution of known concentration and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution
and standard solution, respectedly, at 327 nm and 427 nm
as directed under the Ultraviolet-visible Spectrophotometry using dissolution solution as the control solution..
The dissolution rate (%) of Ergotamine Tartrate Tablets
in 30 minutes is not less than 75%.
of the Content Uniformity Test when the test is performed with Ergotamine Tartrate Tablets according to the
Assay.
Ergotamine Tartrate Tablets. Weigh accurately a portion
of the powder, equivalent to about 10 mg of ergotamine
tartrate [(C33H35N5O5)2C4H6O6], add 50.0 mL of the internal standard and 300 mL of a mixture of acetonitrile
and water (55 : 45) and sonicate for 10 minutes. Add a
mixture of acetonitrile and water (55 : 45) to make exactly 500 mL, mix and filter. Discard the first 10 mL of the
filtrate and use subsequent filtrate as the test solution.
Separately weigh accurately about 10 mg of Ergotamine
Tartrate RS, previously dried at 60 C for 4 hours in vacuum, dissolve in a mixture of acetonitrile and water
(55 : 45) to make exactly 50 mL. Pipet exactly 5 mL of
this solution, add 5.0 mL of the internal standard solution
and add a mixture of acetonitrile and water (55 : 45) to
make exactly 50 mL. Use this solution as the standard
Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS ,
of the peak areas of Ergotamine Tartrate to that of the internal standard, respectively.
Amount (mg) of ergotamine tartrate

(C33H35N5O5)2C4H6O6 = amount (mg) of Ergotamine
Tartrate RS
QT
QS
Internal standard solutionDissolve 40 mg of Ergonobine Maleate in 250 mL of a mixture of acetonitrile

Erythromycin
O
H3C
CH3
H3C
OH
HO
OH
OH
CH3
CH3
H3C
O
O
H3C
CH3
O
H3C
CH3
O
O
CH3
CH3
O
OH
CH3
C37H67NO13: 733.93
Erythromycin is a macrolide substance having antibacterial activity produced by the growth of Saccharopolyspora erythraea.
Erythromycin contains not less than 850 g (potency)
per mg of erythromycin (C37H67NO13), calculated on the
anhydrous basis.
Description Erythromycin is a white to light yellowwhite powder, is odorless, and has a bitter taste.
Erythromycin is freely soluble in methanol, in ethanol, or
in acetone, soluble in ether, and very slightly soluble in
water.
Identification (1) The melting point of Erythromycin
KP 9 363
is between 133 C and 138 C (decomposition).
(2) To 5 mg of Erythromycin add 2 mL of sulfuric acid, and mix with gently shaking: the red-brown color develops.
(3) To 3 mg of Erythromycin add 2 mL of acetone,
and add 2 mL of hydrochloric acid: the orange color develops and the color turns immediately to red to dark
purple.
(4) Dissolve each of Erythromycin and Erythromycin
RS in chloroform to make 1 % solution. Determine the
infrared spectra of these solutions, as directed in the solution method under the Infrared spectrophotometry:
the same wave numbers.

Mobile phase: The mixture of methanol and 0.067
mol/L of potassium dihydrogen phosphate (3:2).
Erythromycin Estolate
O
H3C
CH3
H3C
OH
HO
OH
CH3
CH3
H3C
O
[ ] 20
D

: -71 ~ -78 (1.0 g
calculated on the anhydrous basis, ethanol, 50 mL, 100
mm).
Sterility Test It meets the requirement, when Erythromycin is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Erythromycin is used in a sterile preparation. Weigh appropriate
amount of Erythromycin, dissolve in water, make the solution so that each mL contains 1.0 mg, and use the solution as the test solution. Use 5 mL of this solution for the
test. The amount of injection is 1.0 mL of the test solution per kg of body weight of rabbit.
Erythromycin and Erythromycin RS, dissolve each in 25
mL of methanol, and add the mobile phase to make exactly 50 mL, and use these solutions as the test solution
with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak area of erythromycin, AT and AS.
Amount [g (potency)] of erythromycin (C37H67NO13)

= amount [g (potency)] of Erythromycin RS
AT
AS
CH3
O
H3C
CH3
O
CH3

of Erythromycin in 150 mL of water is between 8.0 and
10.5.
H3 C
O
CH3
O
OH
CH3
C12H25OSO3H
CH3
C40H71NO14C12H25OSO3H: 1056.39
Erythromycin Estolate contains not less than 600 g (potency) per mg of erythromycin (C37H67NO13: 733.93),
Description Erythromycin Estolate is a white crystalline powder or powder, is odorless, and has a bitter taste.
Erythromycin Estolate is sparingly soluble in methanol
or in ethanol, and very slightly soluble in water or in
benzene.
Identification Dissolve each of Erythromycin Estolate
and Erythromycin Estolate RS in chloroform to make
1 % solution. Determine the infrared spectra of these solutions, as directed in the solution method under the
Infrared spectrophotometry: both spectra exhibit similar
g of Erythromycin Estolate in 10 mL of water is between
4.5 and 7.0.
direct titration).
Assay Perform the test according to Assay in Erythromycin. Weigh accurately an appropriate amount of of
Erythromycin Estolate, dissolve in 25 mL of methanol,
solution so that each mL contains 1.0 mg (potency), and
allow this solution to stand in 60 C water bath for 2
hours or at room temperature for 16 ~ 18 hours, and use
this solution as the test solution.
Erythromycin Ethylsuccinate
O
H3C
CH3
H3C
OH
HO
OH
CH3
CH3
H3C
O
O
H3C
H3C
CH3
O
O
CH3
CH3
CH3
CH3
O
CH3
OH O
C43H75NO16: 862.05
Erythromycin Ethylsuccinate is a derivative of erythromycin.
Erythromycin Ethylsuccinate contains not less than 765
g (potency) per mg of erythromycin (C37H67NO13:
Description Erythromycin Ethylsuccinate is a white
powder, and is odorless.
Erythromycin Ethylsuccinate is freely soluble in methanol, soluble in ethanol, sparingly soluble in acetone,
slightly soluble in ether, and practically insoluble in water.
Identification Determine the absorption spectra of
Erythromycin Ethylsuccinate and Erythromycin Ethylsuccinate RS as directed in the paste method under Infrared Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wave numbers.
pH of the solution so that it will be 7.8 to 8.0.

6538 P.
(3) Weigh accurately about 50 mg (potency) of Erythromycin Ethylsuccinate, dissolve in 50 mL of methanol,
and add 0.1 mol/L phosphate buffer solution, pH 8.0 to
make exactly 100 mL. Take exactly a suitable amount of
this solution, add 0.1 mol/L phosphate buffer solution,
pH 8.0 to make solutions so that each mL contains 20.0
g (potency) and 5.0 g (potency), and use these solutions as the high concentration test solution and low concentration test solution, respectively. Separately, weigh
accurately about 25 mg of Erythromycin RS, dissolve in
25 mL of methanol, add 0.1 mol/L phosphate buffer solution, pH 8.0 to make exactly 100 mL, and use this solution as the standard stock solution. Keep the standard
stock solution at not exceeding 5 C and use within 7
days. Take exactly a suitable amount of the standard
stock solution before use, add 0.1 mol/L phosphate buffer solution, pH 8.0 to make solutions so that each mL
Erythromycin Lactobionate
O
H3C
CH3
OH
HO

g of Erythromycin Ethylsuccinate in 10 mL of water is
OH
H3C
H3C
O
CH3
Pyrogen Test It meets the requirement, when Erythromycin Ethylsuccinate is used in a sterile preparation,.
Weigh an appropriate amount of Erythromycin Ethylsuccinate, suspend in water to make the solution so that each
mL contains 50 mg, and use the suspension as the test
suspension. Inject 0.1 mL of this suspension into a muscle of a leg. The amount of injection is 1.0 mL of the test
solution per kg of body weight of rabbit.
direct titration).
Assay The Cylinder-plate method method (1) Agar
media for seed and base layer- Use the medium in I 2 1)
2 under Microbial Assay for Antibiotics. Adjust the
(2)
CH3
HO
CH3
H3CO
CH3
O
HOH2C
OH
O
O
CH3
Sterility Test It meets the requirement, when Erythromycin Ethylsuccinate is used in a sterile preparation.
H H OH H
H3C
CH3
C C C
OH O H
OH
COOH
OH OH
O
OH
OH
CH3
C37H67NO13C12H22O12: 1092.22
Erythromycin Lactobionate contains not less than 570 g
(potency) per mg of erythromycin (C37H67NO13: 733.93),
Description Erythromycin Lactobionate is a white
powder.
Erythromycin Lactobionate is sparingly soluble in ethanol, in methanol or in water, and very slightly soluble in
benzene.
Identification (1) To 5 mg of Erythromycin Lactobionate add 2 mL of sulfuric acid, and mix with gently shaking: the red-brown color develops.
(2) To 3 mg of Erythromycin Lactobionate add 2 mL
of acetone, and add 2 mL of hydrochloric acid: the
KP 9 365
orange color develops and the color turns immediately to
red to dark purple.
(3) Determine the absorption spectra of Erythromycin Lactobionate and Erythromycin Lactobionate RS as
directed in the paste method under Infrared Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wave numbers.
Erythromycin Stearate
O
H3C
CH3
H3C
OH
HO
OH
OH
CH3
CH3
H3C
O
Sterility Test It meets the requirement, when Erythromycin Lactobionate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Erythromycin Lactobionate is used in a sterile preparation.
Weigh an appropriate amount of Erythromycin Lactobionate, dissolve in water, make the solution so that each
mL contains 2.5 mg (potency), and use the solution as
the test solution. Inject 1.2 mL of this solution per kg of
rabbit body weight of rabbit.
direct titration).
(2)
6538 P.
(3) Weigh accurately about 50 mg (potency) of Erythromycin Lactobionate, dissolve in 50 mL of methanol,
exactly 100 mL, and if necessary, allow to stand for 3
hours at room temperature. Take exactly a suitable
amount of this solution, add 0.1 mol/L phosphate buffer
solution, pH 8.0 to make solutions so that each mL contains 20.0 g (potency) and 5.0 g (potency), and use
these solutions as the high concentration test solution and
the low concentration test solution, respectively. Separately, weigh accurately about 25 mg of Erythromycin
RS, dissolve in 25 mL of methanol, add 0.1 mol/L phosphate buffer solution, pH 8.0 to make exactly 100 mL,
and use this solution as the standard stock solution. Keep
the standard stock solution at not exceeding 5 C and use
standard stock solution before use, add 0.1 mol/L phosphate buffer solution, pH 8.0 to make solutions so that
each mL contains 20.0 g (potency) and 5.0 g (potency),
and use these solutions as the high concentration standard solution and the low concentration standard solution,
respectively. Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed
under Microbial Assay for Antibiotics.
H3C

of Erythromycin in 10 mL of water is between 5.0 and
7.5.
CH3
O
H3C
CH3
O
CH3
CH3
O
O
OH
CH3
HO
C55H103NO15: 1018.40
Erythromycin Stearate contains not less than 500 g (potency) per mg of erythromycin (C37H67NO13: 733.93),
Description Erythromycin Stearate is a white powder,
is odorless, and has a little bit of bitter taste.
Erythromycin Stearate is freely soluble in ethanol, soluble in ether, sparingly soluble in acetone, slightly soluble in methanol, and practically insoluble in water.
Erythromycin Stearate and Erythromycin Stearate RS as
directed in the paste method under Infrared Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wave numbers.
(2) Weigh about 10 mg each of Erythromycin Stearate and Erythromycin RS, dissolve each in 5 mL of
chloroform, and use these solutions as the test solution
with these solutions as directed under Thin-layer Chromatography. Spot 10 L of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with the mixture of nbutanol, acetic acid and water (3:1:1), and air-dry the
plate. Then allow the plate to expose to iodine vapor or
spray 10 % sulfuric acid solution. The spots obtained
from the test solution are the same with the corresponding spots from the standard solution in the Rf value.
of Erythromycin Stearate in 10 mL of water is between
6.0 and 11.0.
direct titration).
(2)

6538 P.
(3) Weigh accurately about 50 mg (potency) of Erythromycin Stearate, dissolve in 50 mL of methanol, and
exactly 100 mL. Take exactly a suitable amount of this
solution, add 0.1 mol/L phosphate buffer solution, pH 8.0
to make solutions so that each mL contains 20.0 g (potency) and 5.0 g (potency), and use these solutions as
the high concentration test solution and the low concentration test solution, respectively. Separately, weigh accurately about 25 mg of Erythromycin RS, dissolve in 25
mL of methanol, add 0.1 mol/L phosphate buffer solution,
pH 8.0 to make exactly 100 mL, and use this solution as
the standard stock solution. Keep the standard stock solution at not exceeding 5 C and use within 7 days. Take
exactly a suitable amount of the standard stock solution
before use, add 0.1 mol/L phosphate buffer solution, pH
8.0 to make solutions so that each mL contains 20.0 g
(potency) and 5.0 g (potency), and use these solutions
as the high concentration standard solution and the low
concentration standard solution, respectively. Perform
the test with these solutions according to the Cylinderplate method (I 8) as directed under Microbial Assay for
Antibiotics.
Estazolam
N
N
N
Cl
C16H11ClN4: 294.74
Estazolam, when dried, contains not less than 98.5% and
not more than 101.0% of estazolam (C16H11ClN4).
Description Estazolam is a white to pale yellowish
white crystals or crystalline powder, is odorless and has a
bitter taste.
Estazolam is soluble in methanol or acetic anhydride,
sparingly soluble in ethanol, and practically insoluble in
water or ether.
Identification (1) Dissolve 10 mg of Estazolam in 3
mL of sulfuric acid: the solution shows a yellow-green
fluorescence under ultraviolet light (main wavelength:
365 nm).
(2) Determine absorption spectra of solutions of Es-
tazolam and Estazolam RS, respectively, in 1 mol/L hydrochloric acid TS (1 in 100000) as directed under the
(3) Perform the test with Estazolam as directed under
the flame Coloration Test (2): a green color appears.
Melting Point

g of Estazolam in 10 mL of ethanol: the solution is clear
and colorless.
(2) ChlorideDissolve 1.0 g of Estazolam in 10 mL
of ethanol by heating, add 40 mL of water, cool with
shaking in ice-water, allow to stand to attain ordinary
temperature and filter. To 30 mL of the filtrate, add 6 mL
of dilute nitric acid and water to make 50 mL and perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS and 6 mL of ethanol (not more than
0.015%).
(3) Heavy metalsProceed with 1.0 g of Estazolam
Estazolam according to Method 3 and perform the test
Prepare the test solution with 1.0 g of Estazolam according to Method (not more than 2 ppm).
(5) Related substancesDissolve 0.2 g of Estazolam
in 10 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add methanol to make exactly 200 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with
fluorescent indicator for Thin-layer chromatography. Develop the plate with a mixture of hexane, chloroform and
methanol (5 : 3 : 1) to a distance of about 10 cm and airdry the plate. Examine the plate under ultraviolet light
(main wavelength: 254 nm): any spot other than the principal spot from the test solution are not more intense than
the principal spot from the standard solution.
hours).
Assay Weigh accurately about 0.25 g of Estazolam,
previously dried, dissolve in 100 mL of acetic anhydride
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, endpoint detection method in titrimetry),
until the solution changes to the second equivalence
point. Perform a blank determination and make any necessary correction.
KP 9 367

= 14.737 mg of Cl6H11ClN4
Estradiol
H3C
mL. Pipet exactly 10 mL each of these solutions, add 5.0

mL of the internal standard solution, 100 mL of methanol
and add water to make exactly 200 mL and use these solutions as the standard solutions. Perform the test with 25
and QS , of the peak area of Estradiol to that of the internal standard for the test solution and the standard solution, respectively.
OH
H
Amount(mg) of estradiol (C18H24O2)

=5C
QT
QS
C18H24O2: 272.38
C : Final concentration of Estradiol in the standard

solution (g/mL)
Estradiol, when dried, contains not less than 97.0% and

not more than 103.0% of estradiol (C18H24O2).
Internal standard solutionA solution of ethylparabene in methanol (0.6 in 1000).
Description Estradiol is a white crystal or crystalline

Estradiol is freely soluble in dioxane, soluble in acetone,
sparingly soluble in ethanol, slightly soluble in sesame
oil and practically insoluble in water.
(55 : 100).
System suitability
above operating conditions, internal standard and the Estradiol and estrone are eluted in this order with the resolution between the peaks being not less than 2.0.
under the above operating conditions, the relative standard of the ratios of peak area of Estradiol is not more
than 2.0%.
HO

solutions of Estradiol and Estradiol RS, respectively, in
ethanol (1 in 20000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
intensities of absorption at the same wavelengths. The
difference of absorption maxima in each absorption spectra is not less than 3.0% at about 280 nm.
(2) Determine the infrared spectra of Estradiol and
Estradiol RS as directed in the paste method under the
83(after drying, 0.1 g, dioxane, 10 mL, 100 mm).
Melting Point
Water Not more than 3.5% (0.5 g, volume titration, direct titration).
Assay Weigh accurately about 0.1 g of Estradiol and
dissolve in methanol to make exactly 250 mL. Pipet exactly 10 mL of this solution, add 5.0 mL of the internal
standard solution and 100 mL of methanol and water to
make exactly 200 mL and use this solution as the test solution. Separately, weigh accurately a sufficient amount
each of Estradiol RS (formerly determined water contents as directed under water determination assay) and
Estrone RS and dissolve separately in methanol to contain about 400 g of Estradiol and 240 g of Estrone in 1

tight containers.
Estradiol Benzoate
H3C
OH
H
H
C
O

intense than the principal spot from the standard solution.
C25H28O3: 376.49
Estradiol Benzoate, when dried, contains not less than
97.0% and not more than 101.0% of estradiol benzoate
(C25H28O3).
Description Estradiol Benzoate is a white, crystalline
Estradiol Benzoate is sparingly soluble in acetone,
slightly soluble in methanol, ethanol or ether, and practically insoluble in water.
Identification (1) Take 2 mg of Estradiol Benzoate,
add 2 mL of sulfuric acid: a yellowish green color with a
blue fluorescence is produced and the color of the solution changes to light orange on the careful addition of 2
mL of water.
(2) Determine the infrared spectra of Estradiol Benzoate and Estradiol Benzoate RS, previously dried, as directed in the potassium bromide disk method under the
58 (after drying, 0.1 g, acetone, 10 mL, 100 mm).
Melting Point
Purity (1) 3,17-EstradiolDissolve 10.0 g each of

Estradiol Benzoate and Estradiol Benzoate RS in acetone
to make exactly 200 mL each and use these solutions as
Pipet exactly 2 mL each of the test solution and the standard solution in separate glass-stoppered test tube, add
boiling stones, evaporate the acetone by heating on a water-bath and dry the residue in a desiccator (in vacuum,
P2O5) for 1 hour. Add 1.0 mL of dilute iron-phenol TS to
each test tube. Stopper the test tubes loosely, heat for 30
seconds in a water-bath, shake in a water-bath for several
seconds and heat for 2 minutes. Cool the solutions in ice
for 2 minutes, add 4.0 mL of diluted sulfuric acid (7 in
20) and mix well: the solution obtained from the test solution has no more color than that from the standard solution.
(2) Related substancesDissolve 40 mg of Estradiol
Benzoate in 2 mL of acetone and use this solution as the
test solution. Pipet exactly 1 mL of this solution, add acetone to make exactly 100 mL and use this solution as the
directed under the Thin-layer chromatography. Spot 10
a plate of silica gel with fluorescent indicator for Thinlayer chromatography, develop the plate with a mixture
of chloroform and diethylamine (19 : 1) to a distance of
about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot other

P2O5, 4 hours).
Assay Weigh accurately about 10 mg each of Estradiol
Benzoate and Estradiol Benzoate RS, previously dried
and dissolve each in methanol to make exactly 20 mL.
Pipet exactly 5 mL each of these solutions, add 5 mL of
the internal standard solution, then add methanol to make
and QS , of the peak area of Estradiol Benzoate to that
of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of estradiol benzoate (C25H28O3)

= amount (mg) of Estradiol Benzoate RS
QT
QS
Internal standard solutionA solution of Progesterone in methanol (13 in 80000).

about 35 C.
3).
time of Estradiol Benzoate is about 10 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, the internal standard and Estradiol Benzoate are eluted in this order with the resolutions between their peaks being not less than 9.
operating conditions, the relative standard deviations of
the ratios of the peak area of Estradiol Benzoate to that
tight containers.
KP 9 369
Estradiol Benzoate Injection

Estradiol Benzoate Injection is an oily solution for injection. Estradiol Benzoate Injection contains not less than
90.0% and not more, than 110.0% of the labeled amount
of estradiol benzoate (C25H28O3: 376.49).
Method of Preparation Prepare as directed under Injections, with Estradiol Benzoate.
Description
oily liquid.
Estradiol Benzoate Injection is a clear,

ratios, QT and QS , of the peak area of Estradiol Benzoate to that of the internal standard for the test solution
= amount (mg) of Etradiol Benzoate RS QT
QS
Internal standard solutionA solution of methylparaben in methanol (1 in 2000).
Mobile phase: A mixture of acetonitrile and 0.023
mol/L ammonium phosphate solution (70 : 30).
time of Estradiol Benzoate is about 10 minutes.
System suitability
with 20 L of the standard solution, as diredcted under
the above operating conditions, the internal standard and
Estradiol Benzoate are eluted in this order with a resolution between their peaks being not less than 5.0
under the above conditions, relative standard deviation of
the ratio of the peak area is not more than 2.0%.
Identification To a volume of Estradiol Benzoate Injection, equivalent to 1 mg of Estradiol Benzoate according to the labeled amount, add chloroform to make 5 mL
and use this solution as the test solution. Separately, dissolve 1 mg of Estradiol Benzoate RS in 5 mL of chloroform and use this solution as the standard solution Perform the test with the test solution and the standard solution as directed under the Thin-layer chromatography.
for Thin-layer chromatography. Develop the plate with
dichloromethane to a distance of about 15 cm and air-dry
the plate. Then develop the plate with a mixture of chloroform and methanol (99 : 1) to a distance of about 15
(main wavelength: 254 nm): the principal spots obtained
from the test solution and the spot obtained from the
standard solution show the same Rf value.

It
Estradiol Benzoate Injection

(Aqueous Suspension)
Assay Measure exactly a volume of well-mixed Estradiol Benzoate Injection (aqueous suspension), equivalent
to about 10 mg of estradiol benzoate (C25H28O3), dissolve the crystal with an appropriate volume of methanol
and add methanol to make exactly 100 mL. Pipet exactly
10 mL of this solution, add exactly 20 mL of the internal
standard solution, add methanol to make 100 mL and use
this solution as the test solution. Separately, weigh accurately about 10 mg of Estradiol Benzoate RS, previously
dried in desiccator (in vacuum, P2O5) for 4 hours, and
prepare the standard solution in the same manner as directed for the preparation of the test solution. Perform
the test with 20 L of the test solution and the standard
Estradiol Benzoate Injection (Aqueous Suspension) is an

aqueous suspension for injection. Estradiol Benzoate Injection (Aqueous Suspension) contains not less than
of estradiol benzoate (C25H28O3: 376.49).
Method of Preparation Prepare as directed under Injections, with Estradiol Benzoate.
Description Estradiol Benzoate Injection (Aqueous
Suspension) produces a white turbidity on shaking.
Identification Extract a volume of Estradiol Benzoate
Injection (Aqueous Suspension), equivalent to 1 mg of

Estradiol Benzoate according to the labeled amount, with
5 mL of chloroform and use this extract as the test solution. Separately, dissolve 1 mg of Estradiol Benzoate RS
in 5 mL of chloroform and use this solution as the standard solution. Perform the test with the test solution and
chromatography. Spot 50 L each of the test solution and
the standard solution on a plate of silica gel with fluorescent indicator for Thin-layer chromatography. Develop
the plate with a mixture of chloroform and methanol
Examine under ultraviolet light (mail wavelength: 254
nm): the principal spots obtained from the test solution
and standard solution show the same Rf value.
Assay Measure exactly a volume of well-mixed Estradiol Benzoate Injection (Aqueous Suspension), equivalent to about 2 mg of estradiol benzoate (C25H28O3), dissolve the crystals with an appropriate quantity of methanol and add methanol to make exactly 20 mL. Pipet exactly 10 mL of this solution, add exactly 10 mL of the internal standard solution, add methanol to make 100 mL
weigh accurately about 10 mg of Estradiol Benzoate RS,
previously dried in desiccator (reduced pressure, phosphorus pentoxide) for 4 hours, add exactly 10 mL of the
internal standard solution and methanol to make 100 mL
and use this solution as the standard solution. Proceed
with the test and standard solutions as directed in the Assay under Estradiol Benzoate.

= amount (mg) of Estradiol Benzoate RS QT 1
QS 5
Internal standard solutionA solution of progesterone in methanol (13 in 100000).
Estradiol Cypionate
Estradiol Cypionate contains not less than 97.0% and not

more than 103.0% of estradiol cypionate (C26H36O3), calculated on the dried basis.
Description Estradiol Cypionate is a white to almost
white, crystalline powder and is ordorless or has a
slightly odor.
Estradiol Cypionate is soluble in ethanol, acetone, chloroform or dioxane, slightly soluble in corn oil and practically insoluble in water.
Estradiol Cypionate and Estradiol Cypionate RS, respectively, in ethanol solution (1 in 10000) as directed under
exhibit the same maximum and minimum absorption at
the same wavelengths. Absorptivities 280 nm, calculated
on the dried basis, do not differ by more than 3.0%.
(2) Determine the infrared spectrum of Estradiol Cypionate and Estradiol Cypionate RS, previously dried, as
exhibit the same intensities of absorption at the same
wavenumbers.
D : Between +39 and
+44 (after drying, 0.2 g, dioxane 10 mL, 100 mm).
Melting Point

hours).
Assay Weigh accurately 10 mg of each of Estradiol
Cypionate and dry Estradiol Cypionate RS, previously
dried, dissolve in 10 mL of the internal standard and use
peak area of Estradiol Cypionate to that of the internal
respectively.
Amount (mg) of estradiol cypionate(C26H36O3)

= amount (mg) of Estradiol Cypionate RS QT
CH3
OCOCH 2CH2
Internal standard solutionDissolve 0.2 g of testosterone benzoate in 100 mL of tetrahydrefuran.
QS
HO
C26H36O3: 396.56
KP 9 371
Columm temperature: A room temperature.
Mobile phase: Dissolve 0.8 g of ammonium nitrate in
300 mL of water and add 700 mL of acetonitrile.
System suitability
above conditions, the resolution between Estradiol Cypionate and the internal standard is not less than 3.0.
times with 10 L of the standard solution, as diredcted
under the above conditions, the relative standard deviation of the ratio of the peak area is not more than 1.5%.
tight containers.
Injection, equivalent to about 10 mg of estradiol cypionate (C26H36O3) according to the labeled amount, transfer
to a 100 mL volumetric flask, rinse the pipet used with
small quantity of tetrahydrofuran, add 10 mL of the internal standard solution, mix and shake and add tetrahydrofuran to make 100 mL and use this solution as the test
Estradiol Cypionate RS and transfer to a 100 mL volumetric flask, add 10 mL of the internal standard solution
and tetrahydrofuran to make 100 mL and use this solution as the standard solution. With the test solution and
the standard solution, proceed as directed in the Assay
under Estradiol Cypionate.
Amount (mg) of estradiol cypionate (C26H36O3)
= amount (mg) of Estradiol Cypionate RS
QT
QS
Internal standard solutionDissolve 0.2 g of testosterone benzoate in 100 mL of tetrahydrofuran.
Estradiol Cypionate Injection

Estradiol Cypionate Injection contains not less than

of estradiol cypionate (C26H36O3: 396.56).
Estradiol Valerate
Method of Preparation Prepare as directed under Injections, with Estradiol Cypionate.
H3C
OCOCH2CH2CH2CH3
H
Identification Transfer a volume of Estradiol Cypionate Injection, equivalent to 5 mg of Estradiol Cypionate

according to the labeled amount, to a glass-stoppered test
tube and add 30 mL of ethanol. Shake the mixture vigorously for 5 minutes, centrifuge until the two layers have
been separated and transfer 50 mL of the ethanol layer
with the aid of a hypodermic syringe to a beaker. Evaporate on a steam-bath to dryness, add 5 mL of potassium
hydroxide solution (1 in 10) and heat in the steam-bath
for 15 minutes and use this solution as the test solution.
Separately, mix 50 mg of sulfanilic acid with 2 mL of 3
mol/L hydrochloric acid, warm the mixture, then cool in
ice-water and slowly add, with agitation, 0.3 mL of sodium nitrate solution (1 in 10). Add this solution to the
test solution: a red color is produced.
It

H
HO
C23H32O3: 356.50
Estradiol Valerate contains not less than 98.0% and not
more than 102.0% of estradiol valerate (C23H32O3).
Description Estradiol Valerate is a white crystalline
powder, is odorless or has a slightly oily odor.
Estradiol Valerate is soluble in castor oil, methanol, benzylbenzoate or dioxane, sparingly soluble in sesame oil
or peanut oil and practically insoluble in water.
Identification Determine the infrared spectra of Estradiol Valerate and Estradiol Valerate RS, prepared by adding chloroform and potassium bromide to Estradiol Valerate or Estradiol Valerate RS, then grinding and drying at
105 o C , respectively: both spectra exhibits similar intensities of absorption at the same wavenumbers.
D : Between +41 and
+47 (0.25 g, dioxane, 10 mL, 100 mm).
Melting Point
Assay Pipet exactly a volume of Estradiol Cypionate
Between 143 C and 150 C (Method 1).

Purity (1) EstradiolDissolve 50 mg of Estradiol Valerate in 10 mL of acetone and use this solution as the
test solution. Separately, dissolve 5 mg of Estradiol Valerate RS in 100 mL of acetone and use this solution as the
the standard solution on a plate of silica gel for Thinlayer chromatography. Then develop the plate with a
mixture of cyclohexane and ethyl acetate (7 : 3) to a distance of about 15 cm and dry the plate at 90 o C for 30
minutes. Spray evenly a solution of sulfuric acid in methanol (3 in 10) on the plate and heat at 90 o C for 30
min: any spot other than the principal spot from the test
solution or the spot corresponding to the Estradiol is not
more intense or not larger than the spot from the standard
solution (not more than 1.0%).
(2) Free acidNeutralize 25 mL of ethanol, in a
conical flask, with 0.01 mol/L sodium hydroxide VS to a
faint blue color, using bromothymol blue TS. Accurately
weigh about 0.50 g of Estradiol Valerate and dissolve Estradiol Valerate in the neutralized ethanol. Titrate rapidly
with 0.01 mol/L sodium hydroxide VS to a faint blue
color. (not more than 0.5% of valeric aid)

= 1.021 mg of C5H10O2
(3) Related substancesDissolve about 0.1 g of Estradiol Valerate in 10 mL of acetone and use this solution
as the test solution. Separately, weigh 10 mg of estradiol
valerate RS and add acetone to make 10 mL. Pipet exactly 0.1 mL, 0.5 mL, 1 mL and 2 mL of this solution and
add acetone to each to make exactly 10 mL and use these
solutions as the standard solutions (1), (2), (3) and (4).
solutions as directed under the Thin-layer chromatography. Spot 20 L each of the test solution and the standard
solutions (1), (2), (3) and (4) on a plate of silica gel for
Thin-layer chromatography. Develop the plate with a
mixture of cyclohexane and ether (4 : 1) to a distance of
about 15 cm and air-dry the plate. Spray evenly sulfuric
acid in ethanol (1 in 10) on the plate, heat the plate until
burn and cool. Examine under ultraviolet light (main wavelength: 254 nm and 366 nm). Compare the intensities
of any spot other than the principal spot from the test solution with those from the standard solution: the relative
intensity is not more than 2.0%.
Water Not more than 0.1% (5 g, volume titration, direct titration).
Assay Weigh accurately about 25 mg each of Estradiol
Valerate and Estradiol Valerate RS, dissolve each in the
internal standard solution to make exactly 25 mL and use

conditions and calculate the ratio, QT and QS , of the
peak area of Estradiol Valerate to that of the internal
standard, for the test solution and the standard solution,
respectively.
Amount (mg) of estradiol valerate(C23H32O3)
= amount (mg) of Estradiol Valerate RS QT
QS
Internal standard solutionTestosterone benzoate

solution in tetrahydrofuran (2 in 1000).
Mobile phase: Dissolve 0.8 g of ammonium nitrate in
300 mL of water, add 700 mL of acetonitrile and mix.
System suitability
above operating conditions, Estradiol Valerate and the internal standard are eluted in this order with the resolution
between their peaks being not less than 3.
tight containers.
Estradiol Valerate Injection

Estradiol Valerate Injection is an oily solution for injection. Estradiol Valerate Injection contains not less than
of estradiol valerate (C23H32O3: 356.50).
Method of Preparation Prepare as directed under Injections, with Estradiol Valerate.
Identification Add 0.5 mL of Estradiol Valerate Injection in 10 mL of hexane and 10 mL of 80% methanol in a
separatory funnel and shake for 2 minutes. Allow to separate two layers. Add 1 mL of phenol TS (dilute 1 mL
with 2 mL of water before use) and 3 mL of sodium carbonate VS (1 in 5): a blue color is observed.
Purity EstradiolWeigh accurately a portion of Es-
KP 9 373
tradiol Valerate, add acetone to make a solution containing 30% of Estradiol according to the labeled amount. To
1.0 mL of this solution add oil labeled as vehicle to make
exactly 10 mL and use this solution as the Estradiol solution. Perform the test with this solution and Estradiol Valerate Injection as directed under the Thin-layer chromatography. Spot 5 L each of solutions on a plate coated
with Thin-layer chromatography silica gel and proceed
as directed in the Purity for Estradiol in Estradiol Valerate: not more than 3.0%.
It

Assay Pipet exactly a volume of Estradiol Valerate injection, equivalent to about 20 mg of estradiol valerate
(C23H32O3) according to the labeled amount. Rinse the
pipet with tetrahydrofuran and add 5.0 mL of the internal
standard solution, dilute with tetrahydrofuran to make
Separately, weigh accurately about 20 mg of Estradiol
Valerate RS, add 5.0 mL of the internal standard solution
and dilute with tetrahydrofuran to make exactly 25 mL
and use this solution as the standard solution. Proceed as
directed for the Assay under Estradiol Valerate.
Amount (mg) of estradiol valerate (C23H32O3)

= amount (mg) of Estradiol Valerate RS
QT
QS
Internal standard solutionTestosterone benzoate

solution in tetrahydrofuran (8 in 1000).

Estriol
CH3
OH
H
Description Estriol is a white, crystalline powder and

is odorless.
Estriol is sparingly soluble in methanol, slightly soluble
in ethanol or dioxane, and practically insoluble in water
or ether.
Identification (1) Dissolve 10 mg of Estriol in 100 mL
of ethanol by warming and use this solution as the test
solution. Evaporate 1 mL of this solution on a water-bath
to dryness, add 5 mL of a solution of sodium pphenolsulfonate in phosphoric acid (1 in 50), heat at
150 o C for 10 minutes and cool: a red-purple color develops.
(2) Dissolve 10 mg each of Estriol and Estriol RS
separately in 100 mL ethanol by warming and determine
absorption spectra as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(3) Determine the infrared spectra of Estriol and Estriol RS, previously dried, as directed in the potassium
bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
62 (after drying, 40 mg, dioxane, 10 mL, 100 mm).
Melting Point
Purity (1) Heavy metalsProceed with 1.0 g of Estriol according to Method 2 and perform the test. Prepare
(2) Related substancesDissolve 40 mg of Estriol in
10 mL of ethanol by warming and use this solution as the
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer chromatography. Spot 5 L each of the test solution
and the standard solution on a plate of silica gel for Thinlayer chromatography. Develop the plate with a mixture
of chloroform, methanol, acetone and glacial acetic acid
the plate. Spray evenly diluted sulfuric acid (1 in 2) on
the plate and heat at 105 C for 15 minutes: any spot other than the principal spot from the test solution are not
OH
H
H
H

hours),
HO
C18H24O3: 288.38
Estriol, when dried, contains not less than 97.0% and not
more than 102.0% of estriol (C18H24O3).
Assay Weigh accurately about 25 mg each of Estriol

and Estriol RS, previously dried, and dissolve separately
in methanol to make exactly 50 mL. Pipet exactly 10 mL

each of these solutions, add exactly 5 mL of the internal
standard solution, add methanol to make 100 mL and use
peak area of Estriol to that of the internal standard for the
Amount (mg) of Estriol (C18H24O3)
= amount (mg) of Estriol RS
QT
QS
Internal standard solutionA solution of methyl

Operating condition
about 25 C.
Mobile phase: A mixed solution of water-methanol
(51 : 49).
time of Estriol is about 10 minutes.
System suitability
System performance: When the test is performed
with 10 L of the standard solution under the above operating conditions, estriol and the internal standard are
eluted in this order and the resolution between their
peaks is not less than 8.
above operating conditions, the relative standard deviations of the peak area of estriol to that of the internal
Estriol Injection
Estriol Injection (Aqueous Suspension) is an aqueous
suspension for injection. Estriol Injection (Aqueous Suspension) contains not less than 90.0% and not more than
110.0% of the labeled amount of estriol (Cl8H24O3:
288.38).
Method of Preparation Prepare as directed under Injections, with Estriol.
Description Shake Estriol Injection (Aqueous Suspension): a white turbidity is produced.

Identification Shake well, take a volume of Estriol Injection (Aqueous Suspension), equivalent to 2 mg of Estriol according to the labeled amount, add ethanol to
Proceed with the test solution as directed in the Identification (1) and (2) under Estriol.
Assay Shake well, pipet a volume of Estriol Injection
(Aqueous Suspension), equivalent to about 5 mg of estriol (C18H24O3) and dissolve in methanol to make exactly 20 mL. Pipet exactly 4 mL of this solution, add 5.0 mL
of the internal standard solution, then add methanol to
make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately about 25 mg of Estriol RS, previously dried at 105 o C for 3 hours and dissolve in methanol to make exactly 100 mL. Pipet exactly
4 mL of this solution, add 5.0 mL of the internal standard
solution, then add methanol to make 50 mL and use this
solution as the standard solution. Proceed as directed in
the Assay under Estriol.
Amount (mg) of estriol (Cl8H24O3)

= amount (mg) of Estriol RS QT 1
QS

benzoate in ethanol (1 in 5000).
Estriol Tablets
Estriol Tablets contain not less than 90.0% and not more
than 110.0% of the labeled amount of estriol (C18H24O3:
288.38).
Method of Preparation Prepare as directed under Tablets, with Estriol.
Identification Weigh a portion of powdered Estriol
Tablets, equivalent to 2 mg of Estriol according to the labeled amount, add 20 mL of ethanol, shake for 10 minutes, centrifuge and use the supernatant liquid as the
test solution. Proceed with the test solution as directed in
the Identification (1) and (2) under Estriol.
KP 9 375
Dissolution Test Perform the test with 1 tablet of Estriol Tablets at 50 revolutions per minute according to
water. Take 20 mL or more of the dissolved solution 30
minutes after starting the test and filter through a membrane filter with pore size of not more than 0.8 m. Discard the first 10 mL of the filtrate, pipet exactly the subsequent V mL of the filtrate, add water to make exactly
V' mL so that each mL contains about 0.1 g of estriol
(C18H24O3) according to the labeled amount and use this
about 10 mg of Estriol RS, previously dried at 105 o C
for 3 hours, dissolve in methanol to make exactly 100
mL, then pipet exactly 5 mL of this solution and add water to make exactly 100 mL. Pipet exactly 2 mL of this
according to the operating conditions as directed in the
Assay under Estriol and determine the peak areas of Estriol, AT and AS , from the test solution and the standard solution, respectively.
The dissolution rate of Estriol Tablets in 30 minutes is
not less than 80%.

of estriol (C18H24O3)
= W S AT V ' 1 9
AS
10
WS : Amount of Estriol RS (mg)

C: Labeled amount of estriol (C18H24O3) in 1 tablet
(mg)

of the Content Uniformity Test when is performed the
test according to the following method. Take one tablet
of Estriol Tablets, add exactly 5 mL of water, disperse
the fine particles with ultrasonic wave, add exactly 15
mL of methanol and shake for 15 minutes. Centrifuge
this solution for 10 minutes, pipet a definite amount of
the supernatant liquid and add methanol to make exactly
a definite volume of solution so that each mL of the solution contains about 5 g of estriol (C18H24O3). Pipet exactly 5 mL of this solution, add exactly 1 mL of the internal standard solution and use this solution as the test
solution. Proceed with 20 L of the test solution as directed in the Assay under Estriol. Use a solution of methyl benzoate in methanol (1 in 40000) as the internal
standard solution. Calculate the mean value from each
ratio of peak areas of 10 samples: the samples conform
to the requirements of the deviation (%) of the mean value and each ratio of peak areas is within 15%. If the deviation (%) exceeds 15% and 1 sample shows deviation
within 25%, repeat the test with 20 samples. Calculate
the deviation (%) of the mean value from each ratio of
peak areas of the 30 samples used in the 2 tests and each
ratio of peak areas: the samples conform to the require-
ments if the deviation exceeds 15%, not more than 1

sample shows deviation within 25%, and no sample
shows deviation exceeding 25%.
Estriol Tablets. Weigh accurately a portion of the powder,
equivalent to about 1 mg of estriol (C18H24O3), add exactly 5 mL of water, disperse the fine particles with ultrasonic wave, shake with 25 mL of methanol for 10 minutes, centrifuge and take the supernatant liquid. Add 25
mL of methanol, repeat the above procedure twice, combine the supernatant liquid, add 5.0 mL of the internal
standard solution, then add methanol to make 100 mL
weigh accurately about 25 mg of Estriol RS, previously
dried at 105 C for 3 hours and dissolve in methanol to
make exactly 100 mL. Pipet exactly 4 mL of this solution,
add 5.0 mL of the internal standard solution, then add
methanol to make 100 mL and use this solution as the
standard solution. Proceed with 20 L each of the test solution and the standard solution as directed in the Assay
under Estriol.
Amount (mg) of estriol (C18H24O3)

= amount (mg) of Estriol RS
QT
1
QS 25

Etacrynic Acid
CH2 O
CH3CH2
OCH2CO2H
Cl
Cl
C13H12Cl2O4: 303.14
Etacrynic Acid, when dried, contains not less than 98.0%
and not more than 101.0% of etacrynic acid
(C13H12Cl2O4).
Description Etacrynic Acid is a white, crystalline
Etacrynic Acid is very soluble in methanol, freely soluble
in ethanol, glacial acetic acid or ether, and very slightly
soluble in water.
Identification (1) Dissolve 0.2 g of Etacrynic Acid in
10 mL of glacial acetic acid and to 5 mL of this solution,
add 0.1 mL of bromine TS: the color of the test solution
disappears. To the remaining 5 mL of the solution, add
0.1 mL of potassium permanganate TS: the color of the

test solution changes to light orange immediately.
(2) Take 10 mg of Etacrynic Acid, add 1 mL of sodium hydroxide TS and heat in a water-bath for 3 minutes. After cooling, add 1 mL of chromotropic acid TS,
and heat in a water-bath for 10 minutes: a deep purple
color develops.
(3) Determine absorption spectra of solutions of Etacrynic Acid and Etacrynic Acid RS, respectively, in methanol (1 in 20000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(4) Perform the test with Etacrynic Acid as directed
Melting Point

g of Etacrynic Acid in 10 mL of methanol: the solution is
(2) Heavy metalsProceed with 1.0 g of Etacrynic

Acid according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(3) ArsenicWeigh 1.0 g of Etacrynic Acid according to Method 3 and perform the test. Add 10 mL of a solution of magnesium nitrate in ethanol (1 in 50), then add
1.5 mL of strong hydrogen peroxide water and fire to
burn (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Etacrynic Acid in 10 mL of ethanol and use this solution as the
the standard solution. Perform the test with the test solution and the standard solution as directed under the Thinlayer chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with
fluorescent indicator for Thin-layer chromatography. Develop the plate with a mixture of chloroform, ethyl acetate and glacial acetic acid (6 : 5 : 2) to a distance of
about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot other
60 o C , 2 hours).
Assay Weigh accurately about 0.1 g of Etacrynic Acid,
previously dried, place in an iodine bottle, dissolve in 20
mL of glacial acetic acid and add exactly 20 mL of 0.05
mol/L bromine VS. To this solution, add 3 mL of hydrochloric acid, stopper tightly at once, shake and allow
to stand in a dark place for 60 minutes. Add carefully 50
mL of water and 15 mL of potassium iodide TS, stopper
tightly at once, shake well and titrate the liberated iodine

with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of
starch TS). Perform a blank determination and make any
= 15.157 mg of C13H12Cl2O4
Etacrynic Acid Tablets

Etacrynic Acid Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of etacrynic
acid (C13H12Cl2O4: 303.14).
Method of Preparation Prepare as directed under Tablets with Etacrynic Acid.
Identification Weigh a portion of powdered Etacrynic
Acid Tablets, equivalent to 0.3 g of Etacrynic Acid according to the labeled amount, add 25 mL of 0.1 mol/L
hydrochloric acid TS and extract with 50 mL of dichloromethane. Filter the dichloromethane extract and evaporate the filtrate on a water-bath to dryness. Proceed with
the residue as directed in the Identification under Etacrynic Acid.
Dissolution Test Perform the test with 1 tablet of Etacrynic Acid Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of water. Take 20 mL or more of the dissolved solution 45 minutes after starting the test, and filter through a
Discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, weigh accurately about 55 mg of Etacrynic Acid RS for Assay, previously dried at 60 o C for 2 hours, dissolve in 10 mL of
methanol, and add water to make exactly 100 mL. Pipet
exactly 5 mL of this solution, add water to make exactly
100 mL, and use this solution as the standard solution.
Determine the absorbances, AT and AS , of the test
solution and the standard solution, respectively, at 277
nm as directed under the Infrared-visible Spectrophotometry.
The dissolution rate of Etacrynic Acid Tablets in 45 minutes is not less than 70%.

of etacrynic acid (C13H12Cl2O4)
= WS
AT
1
45
AS C
WS : Amount of Etacrynic Acid RS (mg)
KP 9 377
C: Labeled amount of etacrynic acid (C13-H12Cl2O4)
in 1 tablet (mg)
Etacrynic Acid Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of etacrynic acid
(C13H12Cl2O4), add 25 mL of 0.1 mol/L hydrochloric acid
TS and extract with three 30 mL volumes of dichloromethane. Filter the dichloromethane extracts through a
pledget of absorbent cotton into an iodine bottle. Wash
the pledget of absorbent cotton with a small amount of
dichloromethane and combine the washing with the extracts. Evaporate this solution on a water-bath to dryness
in a current of air, to the residue, add 20 mL of glacial
acetic acid and proceed as directed in the Assay under
Etacrynic Acid.

= 15.157 mg of C13H12Cl2O4
Ethambutol Hydrochloride
CH 2OH
H
CH 3CH 2
NHCH 2CH 2NH
CH 2OH
CH 2CH 3
2 HCl
C10H24N2O22HCl: 277.23
Ethambutol Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of ethambutol hydrochloride (C10H24N2O22HCl).
Description Ethambutol Hydrochloride is a white crystal or crystalline powder, is odorless, and has a bitter
taste.
Ethambutol Hydrochloride is very soluble in water, soluble in methanol or ethanol, and practically insoluble in
ether.
The pH of a solution of Ethambutol Hydrochloride (1 in
20) is between 3.4 and 4.0.
Identification (1) Take 10 mL of a solution of Ethambutol Hydrochloride (1 in 100), add 0.5 mL of cupric sulfate TS and 2 mL of sodium hydroxide TS: a deep blue
color is observed.
(2) Dissolve 0.1 g of Ethambutol Hydrochloride in 40
mL of water, add 20 mL of picric acid TS and allow to
stand for 1 hour. Collect the precipitate, wash with 50
mL of water and dry at 105 C for 2 hours: the precipitate
melts between 193 C and 197 C.
(3) A solution of Ethambutol Hydrochloride (1 in 30)

+6.1 (after drying, 5.0 g, water, 50 mL, 200 mm).
Melting Point
Between 200 o C and 204 o C .

g of Ethambutol Hydrochloride in 10 mL of water: the
(2) Heavy metalsProceed with 2.0 g of Ethambutol
(3) ArsenicWeigh 1.0 g of Ethambutol Hydrochloride according to Method 1 and perform the test. (not
more than 2 ppm).
(4) 2-AminobutanolDissolve about 50 mg of
Ethambutol Hydrochloride, weighed accurately, in water
solution. Separately, dissolve adequate amount of 2Amino-1-butanol RS, weighed accurately, in water and
dilute sequentially to make a solution containing 5 g per
mL and use this solution as the standard solution. Transfer 10 mL of the test solution into 100 mL Erlenmeyer
flask with glass stopper and add 10 mL of water and 20
mL of boric acid buffer solution. Separately, mix 10.0
mL of the test solution, 10.0 mL of the standard solution,
and 20 mL of Boric acid buffer solution in 100 mL Erlenmeyer flask with glass stopper. While the contents in
two flasks are mixed on shaker, add quickly 10 mL of
Fluorescamine solution and stopper them and mix. Perform the test after exactly 1 minute with these solutions
as directed under the Fluorimetry. Determine the fluorescence intensity at 385 nm of excitation wavelength and
485 nm of emission wavelength: the fluorescence intensity obtained from the test solution is not more than that
of the difference between two solutions (not more than
1.0%).
Boric acid buffer solution : Weigh about 1.24 g of boric
acid, dissolve it in 90 mL of water, adjust with 5 mol/L
sodium hydroxide to pH 9.0, and dilute with water to exactly 100 mL and mix.
Fluorescamine solution : Transfer 5 mg of fluorescamine
into cylinder equipped with stopper and scale line, and
dissolve in 50 mL of acetone.
hours).
Assay Weigh accurately about 0.2 g of Ethambutol
Hydrochloride, previously dried, add 100 mL of glacial
acetic acid and 5 mL of mercury (II) acetate TS for nonaqueous titration, mix with stirring, and titrate with 0.1
mol/L Perchloric acid VS until the color of the solution
changes from blue to blue-green (indicator : methylrosaniline chloride TS). Perform a blank determination, and

= 13.862 mg of C10H24N2O22HCl
Ethambutol Hydrochloride
Tablets
Ethambutol Hydrochloride Tablets contain not less than
of ethambutol hydrochloride (C10H24N2O22HCl: 277.23).
Method of Preparation Prepare as directed under Tablets, with Ethambutol Hydrochloride.
Identification (1) Take a portion of powdered Ethambutol Hydrochloride Tablets, equivalent to 0.1 g of
Ethambutol Hydrochloride according to the labeled
amount, add 3 mL of methanol in a glass motor. Add 5
mL of methanol to make a suspension, then filter through
a funnel lined with a filter paper previously moistened
with methanol and collect the filtrate in a beaker containing 100 mL of acetone. Stir the mixture and allow crystallization to proceed for 15 minutes. Decant the liquid
and gently dry the crystals with the aid of a current of air
until the odor of methanol is no longer detectable. Determine the infrared spectra of this crystals and Ethambutol Hydrochloride RS, previously dried, as directed in the
(2) An aqueous solution (I in 10) of the crystals obtained in (1) responds to Qualitative Tests for chloride.
Purity 2-AminobutanolTransfer adequate number of
Ethambutol Hydrochloride Tablets, equivalent to 400 mg
of Ethambutol Hydrochloride, into beaker, add acetone
upto immersion of all sample, allow to stand for 15 minutes, decant acetone, dry. Powder the tablets removed
the coating, add methanol, mix, dilute to exactly 100 mL
and filter. Pipet exactly 25 mL of the filtrate, dilute with
water to make exactly 200 mL. After 15 minutes filter
with dried filter paper, discard first turbid filtrate, use
subsequent filtrate as the test solution. Then, perform the
Purity (4) under Ethambutol Hydrochloride.
Ethambutol Hydrochloride Tablets at 100 revolutions per
using 900 mL of the 1st fluid of the Disintegration Tests.
Filter after 45 minutes from starting the test and use this
a portion of Ethambutol Hydrochloride RS, previously
dried at 105C for 2 hours and dissolve in water to make
0.1 mg per mL and use this solution as the standard solution. Transfer 1 mL each of the test solution and the standard solution and water to 3 separate centrifuge test tubes
with glass-stopper. Add 5.0 mL of bromocresol green solution and 10.0 mL of chloroform, stoppers and shake the
mixture vigorously. Allow the mixture to separate, discard the upper aqueous layer and filter the 3 chloroform
layers through separate pledges of cotton. Determine the
absorption spectra with these solutions as directed under
the Ultraviolet-visible Spectrophotometry, at the wavelength of maximum absorbance at about 415 nm.
The dissolution rate of Ethambutol Hydrochloride Tablets in 45 minutes should be not less than 75%.
Phosphate bufferDissolve 38.0 g of monobasic sodium phosphate and 2.0 g of anhydrous dibasic sodium
phosphate in water to obtain 1000 mL of solution.
Bromocresol green solutionDissolve 0.2 g of bromocresol green in 30 mL of water and 6.5 mL of 0.1
mol/L sodium hydroxide. Dilute with phosphate buffer to
500 mL, mix and add 0.1 mol/L hydrochloric acid to adjust to a pH of 4.6 0.1.
Assay Weigh and finely powder not less than 20
Ethambutol Hydrochloride Tablets. Dissolve an accurately weighed amount of the powder, equivalent to about 30
mg of Ethambutol Hydrochloride according to the labeled amount, in water, shake to mix, add water to make
exactly 100 mL and filter. Discard 10mL of first filtrate
and use subsequent filtrate as the test solution. Separately,
weigh accurately about 30 mg of Ethambutol Hydrochloride RS, dissolve in and dilte with water to make exactly
Perform the test with exactly 50 L each of the test solution and the standard solution as directed under Liquid
and determine each peak area, AT and AS , respectively.
Mobile phase: A mixture of the solution, prepared by
mixing 1.0 mL of triethylamine with 1000 mL of water
and adjusting with phosphoric acid to pH 7.0, and acetonitrile (1 : 1).
System suitability
with 50 L of the standard solution under the above operating condition, the symmetry factor of the peak of
ethambutol are not less than not more than 2.0.
KP 9 379
above operating conditions, the relative standard deviation of the peak area of ethambutol is not more than
2.0%.
Ethenzamide
O
C
NH2
OCH2CH3
(3) Heavy metalsProceed with 2.0 g of Ethenzamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(4) ArsenicTake 0.40 g of Ethenzamide, add 0.3 g
of potassium nitrate and 0.5 g of anhydrous sodium carbonate, mix thoroughly, ignite the mixture gradually and
cool. Dissolve the residue in 10 mL of dilute sulfuric acid and heat the solution until white fumes begin to evolve.
After cooling, add water carefully to make 5 mL, use this
solution as the test solution and perform the test (not
more than 5 ppm).
(5) SalicylamideDissolve 0.20 g of Ethenzamide in
15 mL of dilute ethanol (2 in 3) and add 2 to 3 drops of
dilute ferric chloride TS: no purple color develops.
hours).
Ethoxybenzamide
C9H11NO2: 165.19
Ethenzamide, when dried, contains not less than 98.0%

and not more than 101.0% of ethenzamide (C9H11NO2).
Description Ethenzamide is a white crystal or crystalline powder, is odorless and tasteless.
Ethenzamide is soluble in ethanol or acetone, slightly soluble in ether, and practically insoluble in water.
Ethenzamide's saturated solution is neutral.
Ethenzamide begins to sublime slightly at about 105 C.
Identification (1) Take 0.5 g of Ethenzamide, add 5
mL of sodium hydroxide TS and heat the mixture gently:
the gas evolved turns moistened red litmus paper to blue.
(2) Take 0.2 g of Ethenzamide, add 10 mL of hydrobromic acid and boil the mixture gently for 1 hour under
a reflux condenser. Cool in ice-water, collect the separated crystalline precipitate, wash with three 5 mL volumes of ice-water and dry in a desiccator (in vacuum, silica gel) for 2 hours: the precipitate melts between 158
C and 161 C.

Assay Weigh accurately about 20 mg each of Ethenzamide and Ethenzamide RS, previously dried and dissolve each in 70 mL of ethanol by warming and after
cooling, add ethanol to make exactly 100 mL. Pipet 5.0
mL each of these solutions, add ethanol to make exactly
standard solution, respectively. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 290 nm as directed under
the Ultraviolet-visible Spectrophotometry, using ethanol
as the blank.
Amount (mg) of ethenzamide (C9H11NO2)

= amount (mg) of Ethenzamide RS
AT
AS

Purity (1) ChlorideDissolve 0.5 g of Ethenzamide
in 30 mL of acetone, add 6 mL of dilute nitric acid and
dilute with water to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control solution as follows: to 0.7 mL of 0.01 mol/L hydrochloric acid VS, add 30 mL of acetone and 6 mL of dilute nitric acid and dilute with water to make 50 mL (not more than
0.050%).
(2) SulfateDissolve 0.5 g of Ethenzamide in 30
mL of acetone, add 1 mL of dilute hydrochloric acid and
dilute with water to make 50 mL. Perform the test using
VS, add 30 mL of acetone and 1 mL of dilute hydrochloric acid and dilute with water to 50 mL (not more than
0.048%).
Anesthetic Ether
CH3CH2OCH2CH3
C4H10O: 74.12
Anesthetic Ether contains not less than 96.0% and not
more than 98.0% (by specific gravity) of ether (C4H10O).
Anesthetic Ether contains small quantities of ethanol and
water. Suitable stabilizers may be added. Anesthetic Ether is not to be used for anesthesia if it has been removed
from the original container for more than 24 hours.
Description Anesthetic Ether is a colorless, clear, mobile liquid, having a characteristic odor. Anesthetic Ether
is miscible with ethanol. Anesthetic Ether is soluble in

water. Anesthetic Ether is highly volatile and flammable.
Anesthetic Ether is slowly oxidized by the action of air
and light, with the formation of peroxides.
The vapor of Anesthetic Ether, when mixed with air and
ignited, may explode violently,
Boiling pointBetween 35 C and 37 C.
Specific Gravity
20
d 20
: Between 0.718 and 0.721.
Purity (1) Foreign odorPlace 10 mL of Anesthetic

Ether in an evaporating dish and allow to evaporate
spontaneously to a volume of about 1 mL: no foreign
odor is perceptible. Drop this residue onto a piece of
clean, odorless filter paper to evaporate the ether: no foreign odor is perceptible.
(2) AcidPlace 10 mL of diluted ethanol (4 in 5) and
0.5 mL of phenolphthalein TS in a glass-stoppered flask
and add 0.02 mol/L sodium hydroxide VS dropwise to
produce a red color which persists after shaking for 30
seconds. Add 25 mL of Anesthetic Ether, stopper the
flask, shake gently and add 0.40 mL of 0.02 mol/L sodium hydroxide VS with shaking: a red color develops.
(3) AldehydeTo 100 mL of water in a glassstoppered flask add 10 mL of Anesthetic Ether and 1 mL
of a solution of sodium bisulfite (1 in 1000), stopper
tightly, shake vigorously for 10 seconds and allow the
mixture to stand in a cool place for 30 minutes, protected
from light. Add 2 mL of starch TS and add dropwise 0.01
mol/L iodine VS until a pale blue color develops. Shake
with about 2 g of sodium bicarbonate to decolorize the
solution and add 1 mL of diluted 0.01 mol/L iodine VS
(9 in 40): a blue color develops. Keep the temperature of
the solution below 18 o C during the procedure.
(4) PeroxidePlace 10 mL of Anesthetic Ether in a
Nessler tube, add 1 mL of a freshly prepared solution of
potassium iodide (1 in 10), shake occasionally for 1 hour,
protecting from light, then add 1 mL of starch TS and
shake well: no color is produced in the aqueous layer and
in the ether layer.
(5) Residue on evaporationEvaporate 50 mL of
Anesthetic Ether and dry the residue at 105 C for 1
hour: the weight of the residue is not more than 1.0 mg.
tight containers with avoiding from filling up and fire.
Store at not exceeding 25 C.
Ethinylestradiol
H3C
HO
CH
OH
Ethinylestradiol, when dried, contains not less than

98.0% and not more than 101.0% of ethinyestradiol
(C20H24O2).
Description Ethinylestradiol is a white to pale yellow
Ethinylestradiol is freely soluble in pyridine or tetrahydrofuran, soluble in ethanol or ether, and practically insoluble in water.
Ethinylestradiol dissolves in sodium hydroxide TS.
Identification (1) Dissolve 2 mg of Ethinylestradiol in
1 mL of a mixture of ethanol and sulfuric acid (1 : 1): a
purplish red color develops with a yellow-green fluorescence. Add carefully 2 mL of water to this solution: the
color of the solution changes to red-purple.
(2) Transfer 20 mg of Ethinylestradiol to a test tube
with glass-stopper, dissolve in 10 mL of a solution of potassium hydroxide (1 in 20), add 0.1 g of benzoyl chloride and shake. Collect the resulting precipitate, recrystallize from methanol and dry in a desiccator (in vacuum,
P2O5): the precipitate melts between 200 C and 202 C.
D : Between 26 and
31 (after drying, 0.1 g, pyridine, 25 mL, 200 mm).
Melting Point Between 180 C and 186 C or Between
142 C and 146 C.
Purity EstroneDissolve 5 mg of Ethinylestradiol in
0.5 mL of ethanol and add 50 mg of m-dinitrobenzene.
Add 0.5 mL of freshly prepared dilute potassium hydroxide-ethanol TS, allow to stand in a dark place for 1 hour
and add 10 mL of ethanol: the solution has no more color
Control solutionProceed in the same manner as mentioned above, omitting Ethinylestradiol.

P2O5, 4 hours).
Assay Weigh accurately about 0.2 g of Ethinylestradiol,
previously dried, and dissolve in 40 mL of tetrahydrofurane. Add 10 mL of a solution of silver nitrate (1 in 20)
and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry).

= 29.640 mg of C20H24O2
C20H24O2: 296.40

tight containers.
KP 9 381
Ethinylestradiol Tablets
Ethinylestradiol Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of ethinylestradiol (C20H24O2: 296.40).
Method of Preparation Prepare as directed under Tablets, with Ethinylestradiol.
Identification (1) Evaporate to dryness 5 mL of the
test solution obtained in Assay and add 2 mL of a mixture of sulfuric acid and ethanol (2 : 1) to the residue: a
light red color with a yellow fluorescence develops. To
the solution, add carefully 4 mL of water: the color of the
solution changes to red-purple.
(2) Evaporate to dryness 10 mL of the test solution
obtained in Assay, add 0.2 mL of acetic acid and 2 mL of
phosphoric acid to the residue and heat in a water-bath
for 5 minutes: a red color with a yellow-green fluorescence develops.
of the Content Uniformity Test when the test is performed according to the following method. Place 1 tablet
of Ethinylestradiol Tablets in a separator, add 10 mL of
the 2nd fluid of test fluids under the Disintegration Test
and shake until the tablet is disintegrated. Add 10 mL of
dilute sulfuric acid and 20 mL of chloroform, shake vigorously for 5 minutes and filter the chloroform layer into a
conical flask through filter paper on which 5 g of anhydrous sodium sulfate is placed. Extract the aqueous
layer with two 20 mL volumes of chloroform, proceed
with the extracts in the same manner as before and combine the filtrates with the previous one. Evaporate gently
the combined filtrate in a water-bath with the aid of a
current of nitrogen, dissolve the residue in exactly 100
mL of methanol and centrifuge, if necessary. Pipet x mL
of the supernatant liquid, add methanol to make exactly
V mL of a solution containing about 0.04 g of ethinylestradiol (C20H24O2) per mL and use this solution as the
of Ethinylestradiol RS, previously dried in a desiccator
(in vacuum, P2O5) for 4 hours, dissolve in methanol, dilute to a volume containing about 0.04 g of ethinylestradiol (C20H24O2) per mL, and use this solution as the
standard solution. Pipet exactly 4 mL of sulfuric acidmethanol TS into three test tubes with glass-stopper, T, S
and B, cool in ice, to each tube, add exactly 1 mL each of
the test solution, the standard solution and methanol,
shake immediately and allow to stand in a water-bath at
30 C for 40 minutes. And allow to stand in a water-bath
at 20 o C for 5 minutes. Perform the test with the test solution and the standard solution as directed under the
Fluorometry. Determine the fluorescence intensities, FT ,
FS and FB , of the test solution, the standard solution

and the blank solution, respectively, using the fluorophotometer at about 460 nm of the excitation and at about
493 nm of the fluorescence.
Amount (mg) of ethinylestradiol (C20H24O2) = amount

(mg) of Ethinylestradiol RS
FT F B
V
1
F S F B 2500 x

Ethinylestradiol Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.5 mg of ethinylestradiol (C20H24O2), place in a 50 mL beaker, add 2 mL of
water, shake well, add 3 mL of chloroform and shake
well again. Add 4 g of siliceous earth for chromatography, mix well until the contents do not stick to the inner
wall of the beaker and use the substance as the sample.
Take the chromatographic column, add the sample with a
funnel and pack in proper hardness. Mix well the sample
sticking to the beaker with 0.5 g of siliceous earth for
chromatography and place in the chromatographic tube.
Wipe off the test solution sticking to the beaker and the
tamping rod with glass wool and place in the chromatographic tube. Push down the sample and press lightly on
the chromatographic column to make the height of the
column, 110 mm to 130 mm. Take 70 mL of chloroform,
rinse the inner wall of the chromatographic tube with a
portion of the chloroform and transfer the remaining portion to the chromatographic tube. Collect the efficient solution at a flow rate not more than 0.8 mL per minute.
After completing the elution, rinse the lower end of the
chromatographic tube with a small quantity of chloroform, add chloroform to make exactly 100 mL and use
this solution as the test solution. Weigh accurately about
10 mg of Ethinylestradiol RS, previously dried in a desiccator (in vacuum, P2O5) for 4 hours and dissolve in
chloroform to make exactly 100 mL. Pipet exactly 5 mL
of this solution and add chloroform to make exactly 100
mL. Use this solution as the standard solution. Transfer
exactly 6 mL each of the test solution and the standard
solution to each separators and add 20 mL of isooctane.
Add exactly 10 mL of a mixture of sulfuric acid and methanol (7 : 3), shake vigorously for 5 minutes, allow to
stand in a dark place for 15 minutes and centrifuge. Perform the test with the resulting color solutions as directed
solution, prepared with 6 mL of chloroform in the same
manner, as the blank. Determine the absorbances, AT
and AS , of the subsequent solutions obtained from the
test solution and the standard solution at 540 nm, respectively.
Chromatographic column: Pack a pledget of glass wool
in the bottom of a column 25 mm in inside diameter and
300 mm in length and place 5 g of anhydrous sodium
sulfate on the glass wool. Separately, place 5 g of siliceous earth for chromatography in a 200-mL beaker,
soak well in 4 mL of 1 mol/L hydrochloric acid TS and
mix uniformly. Put the siliceous earth into the chromato-

graphic column in small portions to make 60 to 80 mm in
length in proper hardness with 1 tamping rod.
Amount (mg) of ethinylestradiol (C20H24O2)
= amount (mg) of Ethinylestradiol RS
AT
1
A S 20
Ethionamide
N
CH2CH3
NH2
C8H10N2S: 166.24
Ethionamide, when dried, contains not less than 98.5%
and not more than 101.0% of ethionamide (C8H10N2S).
Description Ethionamide is yellow crystals or crystalline powder, having a characteristic odor and taste.
Ethionamide is soluble in methanol or glacial acetic acid,
sparingly soluble in ethanol, slightly soluble in ether, and
solutions of Ethionamide and Ethionamide RS, respectively, in methanol (3 in 160000) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Determine the infrared spectra of Ethionamide
and Ethionamide RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry,
Melting Point
without exposure to light, using light-resistant vessels.

Dissolve 0.20 g of Ethionamide in 10 mL of methanol
and use this solution as the test solution. Pipet exactly
0.5 mL of test solution, add acetone to make exactly 100
Separately, pipet exactly 0.2 mL of the test solution, add
acetone to make exactly 100 mL, and use this solution as
the standard solution (2). Perform the test with these solutions as directed under the Thin-layer chromatography.
Spot 10 L each of the test solution and the standard solutions (1) and (2) on a plate of silica gel with fluorescent
indicator for Thin-layer chromatography. Develop the
plate with a mixture of ethyl acetate, hexane and methanol (6 : 2 : 1) to a distance of about 15 cm and air-dry the
plate. Examine the plate under ultraviolet light (main
wavelength: 254 nm): any spot other than the principal
spot obtained with the test solution is not more intense
than the corresponding spot with the standard solution
(1), and the number of the spots other than the principal
spot obtained with the test solution being more intense
than that with the standard solution (2) is not more than
one.
hours).
Assay Weigh accurately about 0.3 g of Ethionamide,
color of the solution changes from orange-red to dark
orange-brown (indicator: 2 mL of -naphtholbenzeine

= 16.624 mg of C8H10N2S
Purity (1) AcidDissolve 3.0 g of Ethionamide in 30

mL of methanol by warming, add 90 mL of water, allow
to stand in ice-water for 1 hour and filter. Take 80 mL of
the filtrate, add 0.8 mL of cresol red TS and 0.20 mL of
0.1 mol/L sodium hydroxide VS: a red color develops.
(2) Heavy metalsProceed with 1.0 g of Ethionamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(3) ArsenicWeigh 1.0 g of Ethionamide and perform according to Method 3. Add 10 mL of a solution of
magnesium nitrate in ethanol (1 in 50), then add 1.5 mL
of strong hydrogen peroxide water and fire to burn (not
more than 2 ppm).
(4) Related substancesProceed this procedure
Ethionamide Tablets
Ethionamide Tablets contain not less than 95.0% and not
more than 110.0% of the labeled amount of ethionamide
(C8H10N2S: 166.24).
Method of Preparation Prepare as directed under Tablets, with Ethionamide.
Identification (1) The test solution used in Assay
shows maximum absorption at 290 nm.
(2) Weigh a sufficient portion of powdered Ethionamide Tablets, equivalent to 1 g of Ethionamide, add 50
mL of methanol. After shaking, filter with porous glass
filter and evaporate the filtrate on a water-bath to dry-
KP 9 383
C7H11NO2: 141.17
ness: the melting point of the residue is not less than 155
C and not more than 164 C.
Dissolution Test Take 1 Tablet of Ethionamide Tablet,
perform the test as directed in Method 1 under the Dissolution Test at 100 revolutions per minute, and using 900
mL of 0.1 mol/L hydrochloric acid as the dissolution
medium. After 45 minutes from starting of the test, take
the dissolved solution, and filter through a membrane filter and dilute the filtrate with the dissolution medium.
The diluted filterate used as the test solution. Separately
weigh accurately the suitable weight of Ethionamide
standard, and dissolve in the dissolution medium to make
exactly the same concentration of the test solution, and
absorbances of the test solution and the standard solution,
respectively, at the maximum absorption wavelength of
Spectrophotometry using dissolution medium as a blank.
The dissolution rate of Ethionamide Tablets after 45 minutes should be not less than 75%.
Ethionamide Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of ethionamide
(C8H10N2S: 166.24) and put into porous filter bottle with
vacuum and extract with ten 10 mL of methanol (complete every filtration). Collect the filtrates and add methanol to make 250 mL. Pipet 5.0 mL of this solution and
add methanol to make 200 mL and use this solution as
the test solution. Separately weigh accurately 0.05g of
Ethionamide RS and add methanol to make 100 mL. Pipet 2.0 mL of this solution and add methanol to make exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the
290 nm as directed under the Ultraviolet-visible Spectrophotometry, using methanol as the blank.
Amount (mg) of ethionamide (C8H10 N 2S)
= amount (mg) of Ethionamide RS
AT
2
AS
Packaging and Storage Preserve in a cool place, wellclosed containers.
Ethosuximide
O
H
N
Ethosuximide contains not less than 98.5% and not more

than 101.0% of ethosuximide (C7H11NO2) calculated on
Description Ethosuximide is a white, paraffin-like solid or powder, is odorless or has a slight, characteristic
odor.
Ethosuximide is very soluble in methanol, ethanol, ether,
or dimethylformamide, and freely soluble in water.
Identification (1) Take 0.2 g of Ethosuximide, add 10
mL of sodium hydroxide TS and boil: the gas evolved
turns a moistened red litmus paper blue.
(2) Dissolve 50 mg of Ethosuximide in 1 mL of ethanol, add 3 drops of a solution of cupric acetate (1 in 100),
warm slightly and add 1 to 2 drops of sodium hydroxide
TS: a purple color is produced.
of Ethosuximide and Ethosuximide RS, respectively, in
g of Ethosuximide in 10 mL of water: the solution is
(2) ChlorideWith 1.0 g of Ethosuximide, perform
(3) Heavy metalsProceed with 1.0 g of Ethosuximide according to Method 1. and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(4) Arsenic Weigh 1.0 g of Ethosuximide and perform the test according to Method 1(not more than 2
ppm).
(5) Acid anhydrideDissolve 0.50 g of Ethosuximide in 1 mL of ethanol, add 1 mL of hydroxylamine
hydrochloride-ferric chloride TS and allow to stand for 5
minutes. Add 3 mL of water, mix and allow to stand for 5
minutes: the red to red-purple color of this solution is not
more intense than that of the following control solution.
Control solutionDissolve 70 mg of succinic anhydride in ethanol to make exactly 100 mL. To 1.0 mL of
this solution, add 1 mL of hydroxylamine hydrochlorideferric chloride TS and proceed in the same manner.
(6) CyanideDissolve 1.0 g of Ethosuximide in 10
mL of ethanol and add 3 drops of ferrous sulfate TS, 1
mL of sodium hydroxide TS and 2 to 3 drops of ferric
chloride TS. Warm gently and acidify with dilute sulfuric
acid: not a blue precipitate and a blue color are produced
within 15 minutes.
O
CH2CH3
CH3
and enantiomer
Water
Not more than 0.5% (2 g, volumetric titra-

tion,direct titration).
Assay Weigh accurately about 0.2 g of Ethosuximide,
dissolve in 20 mL of dimethyl-formamide and titrate
with 0.1 mol/L tetramethylammonium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
necessary connection.

hydroxide VS = 14.117 mg of C7H11NO2
Ethyl Aminobenzoate
O
C
OCH2CH3

hours).
NH2
Benzocaine
Anesthezine
water, 2 drops of phenolphthalein TS and 0.50 mL of

0.01 mol/L sodium hydroxide VS: a red color is produced.
(2) ChlorideDissolve 0.20 g of Ethyl Aminobenzoate in 5 mL of ethanol, add 2 to 3 drops each of dilute
nitric acid and of silver nitrate TS: no change occurs
immediately.
(3) Heavy metalsDissolve 2.0 g of Ethyl Aminobenzoate in 20 mL of ethanol, add 2 mL of dilute acetic
acid and ethanol to make 50 mL and perform the test using this solution as the test solution. Prepare the control
solution as follows: to 2.0 mL of standard lead solution,
add 2 mL of dilute acetic acid and sufficient ethanol to
test with 0.5 g of Ethyl Aminobenzoate: the solution has
no more color than Matching Fluid A.
C9H11NO2: 165.19
Ethyl Aminobenzoate, when dried, contains not less than

99.0% and not more than 101.0% of ethyl aminobenzoate (C9H11NO2).
Description Ethyl Aminobenzoate is a white crystal or
Ethyl Aminobenzoate has a slightly bitter taste, numbing
the tongue.
Ethyl Aminobenzoate is freely soluble in ethanol or in
ether, and very slightly soluble in water.
Ethyl Aminobenzoate dissolves in dilute hydrochloric acid.
Assay Weight accurately about 0.25 g of Ethyl Aminobenzoate, previously dried, dissolved in 10 mL of hydrochloric acid and 70 mL of water, add 10 mL of a solution of potassium bromide (3 in 10) and cool to a temperature below 15 C. Then titrate with 0.1 mol/L sodium
nitrite VS (potentiometric titration or Amperometric titration, Endpoint Detection Methods in Titrimetry).
Each mL of 0.1 mol/L sodium nitrite VS

= 16.519 mg of C9H11NO2
Ethyl Cysteine Hydrochloride

HS
Identification (1) Dissolve 10 mg of Ethyl Aminobenzoate in 1 mL of dilute hydrochloric acid and 4 mL of

water. This solution responds to the Qualitative Tests for
primary aromatic amines.
(2) Dissolve 0.1 g of Ethyl Aminobenzoate in 5 mL
of water with the aid of dilute hydrochloric acid added
drop-wise and add iodine TS drop-wise: a brown precipitate is produced.
(3) Warm 50 mg of Ethyl Aminobenzoate with 2
drops of acetic acid and 5 drops of sulfuric acid: the odor
of ethyl acetate is perceptible.
Purity (1) AcidDissolve 1.0 g of Ethyl Aminobenzoate in 10 mL of neutralized ethanol and add 10 mL of
CH2
OCH 2CH3
HCl
NH2
C5H11NO2SHCl: 185.67
Ethyl Cysteine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of ethyl
cysteine hydrochloride (C5H11NO2SHCl).
Description Ethyl Cysteine Hydrochloride is a white
crystal or crystalline powder, has a characteristic odor,
and has a bitter taste at first with a burning after taste.
Ethyl Cysteine Hydrochloride is very soluble in water,
freely soluble in ethanol, and practically insoluble in ether.
KP 9 385
Ethyl Cysteine Hydrochloride and Ethyl Cysteine Hydrochloride RS, respectively, as directed in the potassium
(2) A solution of Ethyl Cysteine Hydrochloride (1 in
D : Between -10.0 and 13.0 (after drying, 2.0 g, 1 mol/L hydrochloric acid TS,
25 mL, 100 mm)
Purity (1) SulfatePerform the test with 0.6 g of
Ethyl Cysteine Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.011%).
(2) Heavy metalsProceed with 1.0 g of Ethyl
Cysteine Hydrochloride according to Method 1 and perform the test. Prepare the control solution with 1.0 mL of
(3) Related substancesPerform this procedure rapidly. Dissolve 50 mg each of Ethyl Cysteine Hydrochloride and N-ethylmaleimide in 5 mL of mobile phase, allow to stand for 30 minutes and use this solution as the
solution as the standard solution. Perform the test with 2
the test solution and the standard solution by the automatic integration method: a peak area from the test solution with the ratio of the retention time to ethyl cysteine
hydrochloride-N-ethylmaleimide complex from the standard solution being about 0.7 is not larger than the peak
area of ethyl cysteine hydrochloride-N-ethyl-maleimide
complex from the standard solution. Each area of all
peaks other than the peaks of ethyl cysteine hydrochloride-N-ethylmaleimide complex and N-ethylmaleimide
from the test solution is not larger than 1/3 of the peak
area of ethyl cysteine hydrochloride-N-ethylmaleimide
complex from the standard solution.
about 25 C.
potassium phosphate TS and acetonitrile (2 : 1).
time of ethyl cysteine hydrochloride-N-ethylmaleimide
complex is about 4 minutes.
System suitability
System performance: Dissolve 50 mg of Ethyl
Cysteine Hydrochloride, 10 mg of L-cysteine hydrochloride and 50 mg of N-ethyl-maleimide in 25 mL of the
mobile phase and allow to stand for 30 minutes. When
the procedure is run with 2 L of this solution, as directed under the above conditions, L-cysteine hydrochloride-N-ethylmaleimide complex, ethyl cysteine hydrochloride-L-ethylmaleimide complex and N-ethylmaleimide
are eluted in this order and after complete resolution of
each component, with the resolution of the peaks of Lcysteine hydrochloride-N-ethylmaleimide complex and
ethyl cysteine hydrochloride-N-ethylmaleimide complex
being not less than 3.
so that the peak height of ethyl cysteine hydrochlorideN-ethylmaleimide complex obtained from 2 L of the
standard solution is between 10 mm and 20 mm.
the retention time of ethyl cysteine hydrochloride-Nethylmaleimide complex.
P2O5, 5 hours).
Assay Weigh accurately about 0.25 g of Ethyl Cysteine
Hydrochloride, previously dried, transfer into a glassstoppered flask and dissolve in 10 mL of water previously freshly boiled and cooled to a temperature not exceeding 5 C in a stream of nitrogen. Add exactly 20 mL of
50 mmol/L iodine VS, previously cooled to a temperature not exceeding 5 C and allow to stand for 30 seconds,
then titrate with 0.1 mol/L sodium thiosulfate VS, on
cooling below 5 C (indicator: 1 mL of starch TS). Perform a blank determination and make any necessary correction.

= 18.567 mg of C5H11NO2SHCl
Ethylmorphine Hydrochloride
Hydrate
CH3
N
HCl
O
CH3CH2O
H OH
2H2O

C19H23NO3HCl2 H2O: 385.88
Ethylmorphine Hydrochloride Hydrate, when dried, contains not less than 98.0% and not more than 101.0% of
ethylmorphine hydrochloride (C19H23NO3HCl : 349.85).
Description Ethylmorphine Hydrochloride Hydrate is
a white to pale yellow crystal or crystalline powder.
Ethylmorphine Hydrochloride Hydrate is very soluble in
methanol or glacial acetic acid, freely soluble in water,
soluble in ethanol, sparingly soluble in acetic anhydride,
and practically insoluble in ether.
Ethylmorphine Hydrochloride Hydrate is colored by
light.
solutions of Ethylmorphine Hydrochloride Hydrate and
Ethylmorphine Hydrochloride Hydrate RS, separatey, in
water (1 in 10000) as directed under Ultraviolet-visible
(2) Determine the infrared spectra of Ethylmorphine
Hydrochloride Hydrate and Ethylmorphine Hydrochloride Hydrate RS as directed in the potassium bromide
disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Ethylmorphine Hydrochloride Hydrate (1 in 50) responds to the Qualitative Tests (2) for
chloride.
D : Between -103 and 106 (0.4 g calculated on the anhydrous basis, water, 20
mL, 100 mm).
pH Dissolve 0.10 g of Ethylmorphine Hydrochloride
Hydrate in 10 mL of water: the pH of this solution is between 4.0 and 6.0.
Purity
Related substancesDissolve 0.20 g of
Ethylmorphine Hydrochloride Hydrate in 10 mL of diluted ethanol (1 in 2) and use this solution as the test solution. Pipet exactly 0.5 mL of the test solution, add diluted ethanol (1 in 2) to make exactly 100 mL and use
with the test solution and the standard solution as directed under the Thin-layer chromatography. Spot 10 L
plate of silica gel with a fluorescent indicator for Thinlayer chromatography. Develop the plate with a mixture
of dehydrated ethanol, toluene, acetone and strong ammonia water (14 : 14 : 7 : 1) to a distance of about 10 cm
Water Between 8.0% and 10.0% (0.25 g, volume titration, direct titration).
Assay Weigh accurately about 0.5 g of Ethylmorphine
Hydrochloride Hydrate and dissolve in 50 mL of a mixture of acetic anhydride and glacial acetic acid (7 : 3) and

tight containers.
Etilefrine Hydrochloride
OH
C
CH2NHCH2CH3
HCl
H
HO
and enantiomer
C10H15NO2HCl: 217.69
Etilefrine Hydrochloride, when dried, contains not less
than 98.0% and not more than 101.0% of etilefrine hydrochloride (C10H15NO2HCl).
Description Etilefrine Hydrochloride is a white crystal
or crystalline powder, is odorless and has a bitter taste.
Etilefrine Hydrochloride is very soluble in water, freely
soluble in ethanol, and sparingly soluble in glacial acetic
acid.
Etilefrine Hydrochloride is gradually colored to yellowbrown by light.
pHThe pH of a solution of Etilefrine Hydrochloride in water (1 in 10) is between 3.8 and 5.8.
Identification (1) Dissolve 5 mg each of Etilefrine
Hydrochloride and Etilefrine Hydrochloride RS, separately in 100 mL of diluted hydrochloric acid (1 in 1000).
Determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry,
(2) Determine the infrared spectra of Etilefrine Hydrochloride and Etilefrine Hydrochloride RS as directed
(3) A solution of Etilefrine Hydrochloride (1 in 1000)
KP 9 387
Melting Point

g of Etilefrine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) Acidity or alkalinityTo 10 mL of a solution of
Etilefrine Hydrochloride (1 in 50) add 0.1 mL of methylred TS for acid or alkali test and 0.2 mL of 0.01 mol/L
sodium hydroxide VS: a yellow color develops, and the
necessary volume of 0.01 mol/L hydrochloric acid VS to
change the color to red is not more than 0.4 mL.
(3) SulfatePerform the test with 0.85 g of Etilefrine Hydrochloride. Prepare the control solution with
0.020%).
(4) Heavy metalsDissolve 1.0 g of Etilefrine Hydrochloride in 30 mL of water and 2 mL of glacial acetic
acid, adjust with 0.1 mol/L sodium hydroxide TS to a pH
of 3.3, add water to make 50 mL and perform the test.
hours).
Assay Weigh accurately about 0.15 g of Etilefrine Hydrochloride, previously dried, dissolve in 20 mL of glacial acetic acid, add 50 mL of acetic anhydride and titrate
with 0.1 mol/L perchloric acid VS (potentiometric titration, endpoint detection method in titrimetry). Perform a

tight containers.
directed under the Ultraviolet-visible Spectrophotometry,

using diluted hydrochloric acid (1 in 1000) as the blank:
it exhibits a maximum between 271 nm and 275nm.
of the Content Uniformity Test when the test is performed according to the following method. To 1 tablet of
Etilefrine Hydrochloride Tablets add 60 mL of diluted
hydrochloric acid (1 in 1000), and proceed as directed in
the assay.
Amount (mg) of etilefrine hydrochloride

(C10H15NO2HCl)
= W S AT 1
AS
10
WS : Amount of Etilefrine Hydrochloride RS (calculated on anhydrouse basis).

Etilefrine Hydrochloride Tablets. Weigh accurately a portion of the powder, equivalent to about 5 mg of etilefrine
hydrochloride (C10H15NO2HCl), add 60 mL of diluted
hydrochloric acid (1 in 1000) to make exactly 100 mL
and filter. Discard the first 20 mL of the filtrate and use
the subsequent filtrate as the test solution. Separately,
weigh accurately about 50 mg of Etilefrine Hydrochloride RS (previously determined the loss on drying), dissolve in diluted hydrochloride acid (1 in 1000) to make
exactly 100 mL, dilute 10 mL of this solution with diluted hydrochloric acid (1 in 1000) to exactly 100 mL
the test with 20 L each of the test solution and the standard solution as directed under Liquid Chromatography
peak areas, AT and AS , of etilefrine.
Amount (mg) of etilefrine hydrochloride

(C10H15NO2HCl) = amount (mg) of Etilefrine Hydroch-
Etilefrine Hydrochloride Tablets
loride RS AT 1
Etilefrine Hydrochloride Tablets contain not less than

of etilefrine hydrochloride (C10H15NO2HCl: 217.69).
about 40 C.
Mobile phase: Dissolve 5 g of sodium lauryl sulfate
in 940 mL of water and 500 mL of acetonitrile, and adjust the pH to 2.3 with phosphoric acid.
Method of Preparation Prepare as directed under Tablets, with Etilefrine Hydrochloride.

Identification Take a portion of powdered Etilefrine
Hydrochloride Tablets, equivalent to 5 mg of Etilefrine
mL of diluted hydrochloric acid (1 in 1000), shake well,
add 40 mL of diluted hydrochloric acid (1 in 1000) and
filter. Determine the absorption spectrum of the filtrate as
AS
10

time of etilefrine is about 6 minutes.
System suitability
System performance: Dissolve 4 mg of bamethan
sulfate and 4 mg of etilefrine hydrochloride in the mobile
phase to make 50 mL. When the procedure is run with 20
L of this solution under the above operating conditions,
etilefrine and bamethan are eluted in this order with the
resolution between their peaks being not less than 5.
above operating conditions, the relative standard deviation of the peak area of etilefrine is not more than 1.0%.
tight containers.
CH2CH3
CH2
CH2CH3
OH
Amount (%) of methanol or ethanol = 500
C QT
W QS
C: Concentration of ethanol or methanol in the standard solution (mg/mL).

W: Weight of Etodolac in the test solution (mg).
Etodolac
N
H
lution as the standard stock solution Pipet 10.0 mL of the

standard stock solution, add 5.0 mL of the internal standard, dilute with dimethylformamide to make exactly
the standard solution as directed under the Gas Chromatography according to the following conditions, and calculate the ratios, QT and QS , of the peak area of Etodolac to that of the internal standard for the test solution
and the standard solution, respectively. Amount of methanol and ethanol in the portion of Etodolac is not more
than 0.1%, respectively.
and enantiomer
C17H21NO3: 287.35
Etodolac contains not less than 98.0% and not more than
102.0% of etodolac (C17H21NO3), calculated on the anhydrous basis.
Description Etodolac is a white crystalline powder.
Etodolac is freely soluble in acetone or ethanol, and
Identification Determine the infrared spectra of Etodolac and Etodolac RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry,
respectively: both spectra exhibit similar intensity of absorption at the same wavenumbers.
Purity (1) ChlorideDissolve 0.5 g of Etodolac in 30
mL of methanol, add water to make exactly 50 mL, and
use this solution as the test solution. Dissolve 0.42 mL of
0.01 mol/L hydrochloric acid VS in 30 mL of methanol,
add water to make exactly 50 mL, and use this solution
as a control solution (not more than 0.03%).
(2) Heavy metalsProceed with 1.0 g of Etodolac
(3) Limit of methanol and ethanolDissolve about
0.5 g of Etodolac, weighed accurately, in 5.0 mL of the
internal standard solution, and use this solution as the
test solution. Separately, pipet exactly 5 mL each of methanol and ethanol, add dimethylformamide to make exactly 200 mL, pipet 5.0 mL of this solution, add dimethylformamide to make exactly 100 mL, and use this so-
Internal standard solutionDissolve a suitable

quantity of isopropanol in dimethylformamide to make a
solution having a concentration of 2.5 L/mL. Pipet 5.0
mL of this solution, and dilute this solution with dimethylformamide to make exactly 100 mL.
Detector: A flame-ionization detector.
Column: A fused silica capillary column, 0.32 mm in
inside diameter and 25 m in length, coated with a 5 m
film of 1% vinyl5% phenylmethylpolysiloxane for gas
chromatography.
Carrier gas: Helium.
Injection port temperature: 200 C.
Detector temperature: 300 C.
Column temperature: Maintain the temperature of 45
C for 5 minutes, then raise at the rate of 30 C per
minute to 280 C and maintain this temperature for 27
minutes.
System suitability
above operating conditions, methanol, ethanol, and isopropanol are eluted in this order with the resolution between their peaks being not less than 1.0.
(4) Related substancesDissolve 25 mg of Etodolac
in acetonitrile to make exactly 250 mL, and use this solution as the test solution. Perform the test with the test solution as directed under the Liquid Chromatography according to the following conditions. Each peak area of
any peak other than the principal peak from the test solution is not more than 0.5 percent to the total area of all
peaks, and the total area is not more than 2.0 percent.
Content (%) of related substances= 100 AT
AS
KP 9 389
AT : Each peak area of the peaks other than the principle peak.
AS : Total area of all peaks.
Column: A stainless steel column, about 4 mm in inside diameter and about 25 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (3
Mobile phase: Use variable mixtures of Solution A
and Solution B as a mobile phase. First 5 minutes, use
mixture of 60 percent solution A and 40 percent solution
B as the mobile phase. For next 30 minutes, change the
mixture ratio as linear gradient to finally make mixture
of 20 percent solution A and 80 percent solution B. Adjust mobile phase to 40 percent of solution B before injection of the test solution and the standard solution, and
keep re-equilibrium.
Mobile phase A: Mix 0.6 mL of phosphoric acid with
100 mL of water.
Mobile phase B: Mix 0.6 mL of phosphoric acid with
100 mL of acetonitrile.
System suitability
System performance: Dissolve suitable amount
each of Etodolac Related Substance I RS and Etodolac
RS in acetonitrile to make solutions containing 10 g of
Etodolac Related Substance I RS and 0.2 mg of Etodolac
RS per mL, respectively. When the procedure is run with
20 L of this solution, as directed under the above operating conditions, etodolac related substance I and Etodolac are eluted in this order with the resolution between
under the above operating conditions, the relative standard deviation of the ratio of the peak area is not more
than 3%.
direct titration).
Assay Weigh accurately about 0.23 g of Etodolac, dissolve in 60 mL of methanol, and titrate with 0.1 mol/L
tetrabutylammonium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform
a blank determination, and make any necessary correction.
Each mL of 0.1 mol/L tetrabutylammonium

hydroxide VS = 28.736 mg of C17H21NO3
Etodolac Tablets
Etodolac Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of etodolac
(C17H21NO3: 287.36)
Method of Preparation Prepare as directed under Tablets, with Etodolac.
Identification Test The retention time of major peak
of the test solution corresponds to that of the standard solution as obtained in the Assay.
Dissolution Test Take 1 tablet of Etodolac Tablets, perform the test as directed in Method 1 under the Dissolution Test at 100 revolutions per minute, and using 1000
mL of pH 6.8 phosphate buffer as the dissolution medium. After 30 minutes from starting of the test, take 20
mL of the dissolved solution, and filter through a membrane filter with a pore size of 0.8 m or less. Discard
the first 10 mL of the filtrate, and use the subsequent filtrate as the test solution. Seperately weigh accurately 25
mg of etodolac reference standard, and dissolve in the
dissolution medium to make exactly 100 mL. Pipet 5 mL
of this solution, add the dissolution medium to make exactly 50 mL, and use this solution as the standard solution. Determine the absorbances, AT and AS , of the
the maximum wavelength at about 274 nm as directed
under the Ultraviolet-visible Spectrophotometry using
the dissolution medium as a blank. The dissolution rate
of Etodolac Tablets after 30 minutes should be not less
than 80%.
Dissolution rate (%) with respect tothe labeledamount

of etodolac(C17H21NO3 ) = WS
AT 100
AS C
WS : Amount of Etodolac RS (mg)

C: Labeled amount of etodolac (C17H21NO3) in each
tablet (mg).

Take 1 tablet of Etodolac Tablets, and shake with 10 mL
of phosphate buffer until the tablet is disintegrated. Add
phosphate buffer to make exactly 100 mL, and centrifuge
this solution. Pipet x mL of the supernatant liquid, add
phosphate buffer to make exactly V mL to provide a solution that contains about 25 g of etodolac (C17H21NO3)
per mL, and use this solution as the test solution. Separately, weigh accurately 25 mg of etodolac reference
standard, and dissolve in phosphate buffer to make exactly 100 mL. Pipet 10 mL of this solution, add phosphate

buffer to make exactly 100 mL, and use this solution as
the standard solution. Determine the absorbances, AT
and AS , of the test solution and the standard solution,
respectively, at maximum wavelength at about 274 nm as
directed under the Ultraviolet-visible spectrophotometry.
Amount (mg) of etodolac (C17 H 21 NO 3 )
= amount (mg) of Etodolac RS
Etofenamate
O
AT V 1

AS 10 x

Etodolac Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of etodolac
(C17H21NO3), and add 30 mL of a mobile phase. Shake
for 15 minutes, and sonicate 5 minutes for integration.
After cooling, add the mobile phase to make exactly 50
mL. After leaving 10 minutes, pipet 10.0 mL of this solution, then add the mobile phase to make exactly 100 mL,
filter, and use this filtrate as the test solution. Separately,
weigh exactly 20 mg etodolac reference standard and
dissolve in the mobile phase to make exactly 100 mL,
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the
peak areas, AT and AS , of the test solution and the
Amount (mg) of etodolac (C17 H 21NO3 )
= amount (mg) of Etodolac RS
AT
5
AS
Column: A stainless steel column, about 4.6 nm in inside diameter and about 25 cm in length, packed with 3 ~
10 m in particle diameter octadecylsilanized silicagel
for liquid chromatography.
Mobile phase: acetonitrile water phosphate mixture (500 : 500 : 0.25).
System suitability
System performance: Dissolve Etodolac related
substance RS and Etodolac RS in acetonitrile to
make Etodolac related substance RS 10 g and Etodolac RS about 0.2 mg per mL. When the precedure is
run with 20 L of this solution, as directed under the
above operating conditions, Etodolac related substance
and Etodolac are eluted in this order with the resolution between their peaks being not less than 3.0.
times with about 20 L of the standard solution, as directed under the above operating conditions, the relative
standard deviation of the peak areas is not more than 3%.
O
O
OH
NH
CF3
C18H18F3NO4 : 369.34
Etofenamate contains not less than 98.5% and not more
than 101.5% of etofenamate (C18H18F3NO4), calculated
Description Etofenamate is a yellow viscous liquid.
Etofenamate is practically insoluble in water.
Etofenamate is miscible with ethanol or with ethyl acetate.
Identification Determine the infrared spectra of Etofenamate and Etofenamate RS as directed in the liquid film
Purity (1) Heavy metalsProceed with 2.0 g of Etofenamate according to Method 2 and perform the test.
(2) DiethyleneglycolWeigh accurately about 0.2 g
of Etofenamate, add 10 L of internal standard solution
and 2 mL of N-methyltrimethylsilyltrifluoroacetamide,
heat at 50 o C for 30 minutes and use this solution as the
test solution. Separately, pipet 6.0 mg of diethylene glycol, transfer into a 10 mL volumetric flask, add 3 mL of
N-methyltrimethylsilyltrifluroacetamide, heat at 50 o C
for 30 minutes, allow to cool and add Nmethyltrimethylsilyl-trifluoroacetamide to make 10 mL.
Mix 10 L of this solution, 10 L of internal standard solution and 2 mL of N-methyltrimethylsilyltrifluoroacetamide and use this solution as the standard
solution. Perform the test with exactly 0.2 L each of the
test solution and the standard solutions as directed under
Gas Chromatography according to the following conditions, and determine the percentages of peak heights of
diethylene glycol, HT and HS, reference to the peak
height of the internal standard, respectively. (0.1%)
KP 9 391
Internal standard solutionDissolve 6.0 mg of tetracain in hexane to make 10 mL.
Detector: A hydrogen flame-ionization detector
Column: A fused-silica column about 0.20 mm in inside diameter and about 25 m in length, coated the inner
surface with polydimethyldiphenylsiloxane for Gas
Chromatography 0.33 m in thickness.
Column temperature:
Time
Temperature
Rate
(minutes)
(C)
(C /minute)
column
0~13
60150
7
13~19
150300
25
19~34
300
Injector
150
detector
300
Carrier gas: Hydrogen
(3) Related substancesWeigh accurately 50.0 mg
of Etofenamate, dissolve in 30 mL of methanol, add water to make exactly 50 mL and use this solution as the
test solution. Dissolve 10.0 mg of Etofenamate Related
Substance I RS {2-Hydroxyethyl-2-[[3-(trifluoromethyl)
phenyl]amino]benzoate} in methanol to make exactly 20
mL. To 0.2 mL of this solution add a mixture solution of
water and methanol (40 : 60) to exactly 100 mL and use
this solution as the standard solution (1). To 0.2 mL of
the test solution add a mixture solution of water and methanol (40 : 60) to make exactly 100 mL and use this solution as the standard solution (2). Mix 5.0 mL each of
the standard solution (1) and the standard solution (2)
and use this solution as the standard solution (3). Dissolve 10.0 mg of Etofenamate RS for peak identification
(contains etofenamate spiked with about 1% each of related substances II, III, IV, V and VI) in 6.0 mL of methanol and add water to make exactly 10 mL and use this
with exactly 20 L each of the test and standard solutions
(1), (2), (3), and (4) as directed under Liquid Chromatography according to the following conditions, and determine each peak area by the automatic integration method.
For the calculation of contents of related substances II,
IV and VI, multiply each peak area by the corresponding
correction factor, 0.62, 0.45 and 0.77, respectively: the
area of the related substance II in the chromatogram from
the test solution is not more than 1.25 times the area of
the principal peak from the standard solution (2) (0.25%),
each peak area of related substance III, IV, and VI is not
more than the area of the principal peak from the standard solution (2) (each 0.2%), the area of the related substance I is not more than the area of the principal peak
from the standard solution (1) (0.2%), the area of the related substance V is not more than 2.5 times the area of
the principal peak in the chromatogram obtained from
reference solution (b) (0.5%), the peak area of any other
related substance is not more than half the area of the
principal peak with the standard solution (2) (0.1%), the
total area of all peaks other than the principal peak is not
more than 6 times the area of the principal peak from the
standard solution (2) (1.2%). Disregard peaks being not
more than 0.25 times the area of the principal peak from
the standard solution (2) (0.05%). Retention time of etofenamate peak is about 13 minutes and relative retention
time of related substances II, IV, I, VI, III and V with
reference to etofenamate are 0.2, 0.7, 0.85, 1.5, 1.6 and
1.7, respectively.
diameter and 10 cm in length, packed with octadecylsilyl
silica gel for Liquid Chromatography (3 m in particle
diameter).
about 40 o C .
Mobile phase: Program with mobile phase A and
mobile phase B in isocratic or linear gradient as following.
mobile phase A: Dissolve 1.3 g of ammonium phosphate and 4.0 g of tetrabutylammonium hydroxide in 900
mL of water. Adjust pH to 8.0 with dilute phosphoric acid and add water to make 1000 mL.
mobile phase B: methanol
Mobile phase A
Mobile phase B
Time
(vol%)
(vol%)
0~13
40
60
13~20
4010
6090
20~25
10
90
25~26
1040
9060
26~31
40
60
System suitability
System performance: Dissolve 10.0 mg of Etofenamate Related Substance I RS in methanol to make 20
mL. To 0.2 mL of this solution add a mixture of water
and methanol (40 : 60) to make 100 mL. To 5.0 mL of
this solution add 5.0 mL of the solution prepared by dilution of 0.2 mL of the test solution with a mixture of water and methanol (40 : 60) to make 100 mL. When the
above operating condition, resolution between the peaks
of etofenamate and related substance I is not less than 2.3.
direct titration)
Assay Weigh accurately about 3g of Etofenamate, add
20 mL of 2-propanol and 20 mL of 1 mol/L sodium hydroxide VS, heat under reflux for 2 h and cool. Titrate
with 1 mol/L hydrochloric acid VS (indicator : 0.1 mL of
bromthymol blue ). Perform a blank determination and

= 369.35 mg of C18H18F3NO4.
Etoposide
H3CO
O
H
HO
O
O
CH 3
H3CO
HO
OH
O
C29H32O13: 588.56
Etoposide contains not less than 98.0% and not more
than 102.0% of etoposide (C29H32O13), calculated on the
anhydrous basis.
Description Etoposide is a white crystals or crystalline
powder.
Etoposide is sparingly soluble in methanol, slightly soluble in ethanol, and very slightly in water.
Melting pointabout 260 o C
solutions of Etoposide and Etoposide RS, respectively, in
methanol (1 in 10000) as directed under Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Etoposide and
Etoposide RS, according to the paste method under the
D : Between 100 and
105 [0.1 g calculated on the anhydrous basis, methanol,
20 mL, 100 mm].
Purity (1) Heavy metalsProceed with 2.0 g of Etoposide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
(2) Related substancesDissolve 50 mg of Etoposide in 10 mL of methanol and add mobile solution to
make 50 mL and use this solution as the test solution. Pipet 2 mL of the test solution, add the mobile phase to
make 200 mL, and use this solution as the standard solution. Perform the test with exactly with exactly 50 L
each of the test solution and standard solution as directed
under Liquid Chromatography according to the following conditions, and determine each peak area by the automatic integration method: the area of any peak other
than etoposide obtained with the test solution is not

greater than 1/5 times the peak area of etoposide obtained with the standard solution, and the total area of all
peaks other than the peak of etoposide obtained with the
test solution is not larger than 1/2 times the peak area of
etoposide obtained with the standard solution.
and flow rate: Proceed as directed in the operating conditions in the Assay.
System suitability
System performance: Proceed as directed in the
system suitability in the Assay.
Test for the required detectability: Measure exactly 1 mL
of the standard solution, and add the mobile phase to
make exactly 10 mL. Conform that the peak area of etoposide obtained with 50 L of this solution is equivalent
to 7 to 13% of that of etoposide obtained with 50 L of
above operating conditions, the relative standard deviation of the peak area of etoposide is not more than 2.0%.
retention time of etoposide beginning after the solvent
peak.
direct titration).
Residue on ignition Not more than 0.1% (1 g)
Assay Weigh accurately about 25 mg each of Etoposide and Etoposide RS (determined previously the water),
dissolve separately in and dilute with methanol to make
exactly 25 mL each. Pipet 10 mL each of these solutions,
add exactly 5 mL of the internal standard solution and
the mobile phase to make exactly 50 mL and use this solution as the test solution and standard solution, respectively. Perform the test with 50 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and determine the ratios, QT and QS , of the peak
area of etoposide to that of the internal standard.
Amount (mg) of C29H32O13 = WS
QT
QS
WS : Amount of the Etoposide RS, calculated on the

anhydrous basis (mg)
Internal standard solutionA solution

dichlorophenol in methanol (3 in 2500).
of
2,6-
KP 9 393
phenylsilyl silica gel for liquid chromatography (10 m
particle diameter).
about 35 C
Mobile phase: Dissolve 6.44 g of sodium sulfate decahydrate in diluted glacial acetic acid (1 in 100) to make
1000 mL, and add 250 mL of acetonitrile.
Flow rate: Adjust the flow rate so that the retentiontime of etoposide is about 20 minutes.
System suitability
System performance: Dissolve 10 mg of Etoposide
in 2 mL of methanol, add 8 mL of the mobile phase, and
mix well. Add 0.1 mL of diluted glacial acetic acid (1 in
25) and 0.1 mL of phenolphthalein TS, and add sodium
hydroxide TS until the color of the solution changes to
faintly red. After allowing to stand for 15 minutes, add
0.1 mL of diluted glacial acetic acid (1 in 25). When the
peak having the relative retention time of about 1.3 with
respect to etoposide is not less than 3.0.
above operating conditions, the relative standard deviation of the peak areas of etoposide to that of internal
tight containers.
Famotidine
H2N
C
H2N
NH2
N
N
CH2SCH 2CH2
S
O
N
NH2

(2) Determine the infrared spectra of Famotidine and
Famotidine RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
g of Famotidine in 10 mL of 0.5 mol/L hydrochloric acid
TS: the solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 2.0 g of Famotidine
according to Method 2 and perform the test. Prepare
(3) Related substancesDissolve 0.20 g of Famotidine in 10 mL of glacial acetic acid and use this solution
as the test solution. Pipet exactly 1 mL of the test solution and add glacial acetic acid to make exactly 100 mL.
Pipet exactly 1 mL, 2 mL and 3 mL of this solution, add
glacial acetic acid to make exactly 10 mL, respectively
and use these solutions as the standard solutions (1), (2)
and (3). Perform the test with the test solution and the
standard solutions (1), (2) and (3) as directed under the
Thin-layer chromatography. Spot 5 L each of the test
solution and the standard solutions (1), (2) and (3) on a
plate of silica gel (5 to 7 m in particle diameter) with
fluorescent indicator for thin-layer chromatography and
dry in a stream of nitrogen. Develop the plate with a
mixture of ethyl acetate, methanol, toluene and strong
ammonia water (40 : 25 : 20 : 2) to a distance of about 8
principal spot and other than the spot of the starting point
from the standard solution (3). Total intensity of the spots
other than the principal spot and other than the spot of
the starting point from the test solution is not more than
0.5% calculated on the basis of intensities of the spots
from the standard solutions (1) and (2) (each spot is
equivalent to 0.1% and 0.2%, respectively).
C8H15N7O2S3: 337.45
Famotidine, when dried, contains not less than 98.5%
and not more than 101.0% of famotidine (C8H15N7O2S3).
Description Famotidine is a white to yellowish white
crystal.
Famotidine is freely soluble in glacial acetic acid,
slightly soluble in ethanol, and very slightly soluble in
water.
solutions of Famotidine and Famotidine RS in 0.05
mol/L monobasic potassium phosphate TS (1 in 50000)

P2O5, 80 C, 4 hours).
Assay Weigh accurately about 0.3 g of Famotidine,
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination and

= 16.873 mg of C8H15N7O2S3
tight containers.
Famotidine Tablets
Famotidine Tablets contain not less than 94.0% and not
more than 106.0% of the labeled amount of famotidine
(C8H15N7O2S3: 337.45).
Method of Preperation Prepare as directed under Tablets, with Famotidine.
Identification Weigh a portion of powdered Famotidine Tablets, equivalent to 10 mg of famotidine according to the labeled amount, add 50 mL of 0.05 mol/L potassium dihydrogenphosphate TS, shake well and centrifuge. Take 5 mL of the supernatant liquid, add 0.05
mol/L potassium dihydrogen phosphate TS to make 50
mL, and determine the spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry: it
exhibits an absorbance maximum between 263 nm and
267 nm.
and filter through a membrane filter (pore size of not

more than 0.8 m). Discard the first 10 mL of the filtrate,
and use the subsequent filtrate as the test solution. Separately, weigh accurately 20 mg of famotidine RS, add
buffer solution to make exactly 100 mL. Pipet 5.0 mL of
this solution, add the buffer solution to make exactly 50
mL, and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution
and the standard solution at an absorption maximum near
The dissolution rate of Famotidine Tablets in 30 minutes should be not less than 75%.
of famotidine (C8H15N7O2S3)
90
AT
= amount (mg) of Famotidine RS A C
S
C: labeled amount (mg) of famotidine (C8H15N7O2S3)
in 1 tablet.

when the Content Uniformity Test is performed according to the following method
Take 1 tablet of Famotidine Tablets, add 2 mL of water,
shake to disintegrate. Add a suitable amount of methanol
and shake well, then add methanol to make exactly V mL
of a solution containing about 0.2 mg of famotidine
(C8H15N7O2S3) per mL and centrifuge. Pipet exactly 10
mL of the supernatant liquid, add 2.0 mL of the internal
standard solution, add the mobile phase to make exactly
20 mL, and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Famotidine RS,
previously dried in vacuum with P2O5 at 50 C for 4
hours, and dissolve in methanol to make exactly 100 mL.
Pipet exactly 10 mL of this solution, add 2.0 mL of the
internal standard solution, add the mobile phase to make
exactly 20 mL, and use this solution as the standard solution. Perform the test with 5 L each of the test solution
described in the Assay and calculate the ratios, QT and
QS, of the peak area of famotidine to that of the internal
standard.
Assay Take a number of Famotidine Tablets, equivalent to 0.2 g of famotidine (C8H15N7O2S3), add 50 mL of
water and disintegrate by shaking well. Then add 100 mL
of methanol, shake well, add methanol to make exactly
200 mL, and centrifuge. Pipet exactly 5 mL of the surpernatant liquid, add exactly 5 mL of the internal standard solution, add the mobile phase to make exactly 50
weigh accurately about 0.1 g of Famotidine RS, previously dried in vacuum with P2O5 at 80 C for 4 hours,
and dissolve in methanol to make exactly 100 mL. Pipet
exactly 5 mL of this solution, add exactly 5 mL of the internal standard solution, add the mobile phase to make
exactly 50 mL, and use this solution as the standard solution. Perform the test with 5 L each of the test solution
and calculate the ratios, QT and QS, of the peak area of
famotidine to that of the internal standard.
Amount (mg) of famotidine (C8H15N7O2S3)

QT
V
= amount (mg) of Famotidine RS Q 500
S
Internal standard solutionTake 5 mL of a solution

of methyl paraoxybenzoate in methanol (1 in 500) add

about 25 C.
Dissolution Test Perform the test with 1 tablet of Famotidine Tablets at 50 revolutions per minute according
0.1 mol/L phosphate buffer (pH 4.5). Take 20 mL of the
dissolved solution at 30 minutes after starting the test,

QT
S
KP 9 395
Mobile phase: Dissolve 2 g of sodium 1-heptane sulfonate in 900 mL of water, adjust the pH to 3.0 with anhydrous acetic acid, and add water to make 1000 mL. To
this solution, add 240 mL of acetonitrile and 40 mL of
methanol.
time of famotidine is about 6 minutes.
System suitability
System performance: When the precedure is run
above operating conditions, famotidine and internal standard are eluted in this order with the resolution between
the peak area of famotidine is not more than 1.0%.
Famotidine for Injection

Famotidine for injection is a solution for injection which
is dissolved before use. Famotidine for injection contains
not less than 94.0% and not more than 106.0% of the labeled amount of famotidine (C8H15N7O2S3: 337.45).
Method of Preperation Prepare as directed under Injections, with Famotidine.
Description Famotidine for injection occurs as porous
masses or powder.
Identification Weigh a portion of Famotidine for injection, equivalent to 10 mg of Famotidine according to the
labeled amount, dissolve in 50 mL of 0.05 mol/L potassium dihydrogenphosphate TS, to 5 mL of this solution
add 0.05 mol/L potassium dihydrogen phosphate TS to
make 50 mL, and determine the spectrum of this solution
as directed under the Ultraviolet-visible Spectrophotometry: it exhibits the maximum absorbance between 263 nm
and 267 nm.
pH Weigh a portion of Famotidine for injection, equivalent to 20 mg of famotidine according to the labeled
amount, dissolve in 1 mL of water: the pH of this solution is between 4.9 and 5.5.
Purity (1) Clarity and color of solution Weigh a
portion of Famotidine for injection, equivalent to 20 mg
of famotidine according to the labeled amount, dissolve
in 1 mL of water; the solution is clear and colorless.
(2) Related substancesTake a number of Famotidine for injection, equivalent to about 0.1 g of famotidine
(C8H15N7O2S3), dissolve each content in water, wash the
inside of the container with water, combine the solutions
of the contents with the washings, add water to the combined solution to make exactly 100 mL, and use this solution as the test solution. Pipet exactly 1 mL of this solution, add water to make exactly 100 mL, and use this
the following conditions, and determine each peak area
of these solutions by the automatic integration method:
the total area of the peaks other than the major peak from
the test solution is not larger than the major peak from
Proceed with a Detector, column, column temperature,
mobile phase, flow rate, and selection of column as directed in the Assay.
so that the peak height of famotidine obtained from 5 L
of the standard solution is between 5 mm and 10 mm.
the retention time of famotidine after the solvent peak.
Water Not more than 1.5 percent (0.1 g, coulometric
titration).
Baterial Endotoxins Less than 15 EU/mg of Famotidine for injection.
It

Assay Take a number of Famotidine for injection,
equivalent to about 0.1 g of famotidine (C8H15N7O2S3),
dissolve each content in water, wash the inside of the
container with water, combine the solutions of the contents with the washings, add water to the combined solution to make exactly 100 mL. Pipet exactly 5 mL of this
solution, add 5.0 mL of the internal standard solution,
add the mobile phase to make exactly 50 mL, and use
this solution as the test solution. Separately, weigh accurately about 50 mg of Famotidine RS, previously dried in
vacuum with P2O5 at 80 C for 4 hours, dissolve in the
mobile phase to make exactly 50 mL. Pipet exactly 5 mL
of this solution add 5.0 mL of the internal standard solution, add the mobile phase to make exactly 50 mL, and
ratios, QT and QS, of the peak area of famotidine to that
of the internal standard.

QT
S
about 25 C.
Mobile phase: Dissolve 2 g of sodium 1-heptane sulfonate in 900 mL of water, adjust the pH to 3.0 with glacial acetic acid, and add water to make 1000 mL. To this
solution, add 240 mL of acetonitrile and 40 mL of methanol.
time of famotidine is about 6 minutes.
System suitability
System performance: When the precedure is run
above operating conditions, famotidine and internal standard are eluted in this order with the resolution between
deviation of the peak area of famotidine is not more than
1.0%.
H
N
Ai
Amount (%) of related substances = 100 A
s
Ai : each peak area except major peak
As : the sum of all peak area
CH3
H3C
H
O

g of Felodipine in methanol to make exactly 50 mL. Perform the test with this solution as directed under the Ultraviolet-visible Spectrophotometry, using methanol as
the blank: the absorbance at 440 nm is not more than 0.2.
(2) Heavy metalsProceed with 1.0 g of Felodipine
(3) Related substancesPerform the test with 40 L
of the test solution prepared as in the Assay as directed
under the Liquid Chromatography according to the following conditions, and determine each peak area of the
test solution: each peak area except major peak to that of
major peak area is not more than 1.0%, and the sum of
all peak area is not more than 1.5%.

hours).
CH3

Felodipine and Felodipine RS, previously dried, as directed in the potassium bromide disk method under the
intensity of absorption at the same wavenumbers.
(2) The retention time of the major peak in the chromatogram of the test solutoin is same as that of the standard solution, as obtained in the Assay.
Proceed as directed in the Assay.
the retention time of felodipine.
Felodipine
H3C
Description Felodipine is a light yellow to yellow

crystalline powder.
Felodipine is freely soluble in acetone or in ethanol,
slightly soluble in heptane, and practically insoluble in
water.
O
Cl
Cl
and enantiomer
C18H19Cl2NO4: 384.25
Felodipine contains not less than 98.0% and not more

than 101.0% of felodipine (C18H19Cl2NO4), calculated on
the dried basis.
Assay Weigh accurately about 30 mg each of Felodipine and Felodipine RS, add the mobile phase to make
exactly 100 mL, and use these solutions as the test solution and the standard solution. The test solution and the
standard solution are prepared before use. Perform the
according to the following conditions, and determine AT
and AS, of the peak area of felodipine of each solution.
KP 9 397
Amount (mg) of felodipine (C18H19C12NO4)
AT
= amount (mg) of Felodipine RS A
S
Mobile phase: A mixture of phosphate buffer, acetonitrile, and methanol (40 : 40 : 20).
System suitability
System performance: Dissolve 0.15 g of Felodipine in a mixture of 25 mL of tertiary butyl alcohol and
25 mL of 1 mol/L perchloric acid, add 10 mL of 0.1
mol/L ceric sulfate, mix, and allow to stand for 15 minutes. Add 3.5 mL of 10 mol/L sodium hydroxide TS,
and neutralize with 2 mol/L sodium hydroxide TS. Shake
the mixture with 25 mL of methylene chloride in a sparator. Draw off the lower layer, and evaporate it to dryness
under a stream of nitrogen on a water-bath. Dissolve 10
mg of the residue (felodipine oxidation product) and 5
mg of Felodipine RS in the mobile phase to make 100
mL. Pipet 1.0 mL of this solution, and add mobile phase
to make 100 mL. When the procedure is run with 20 L
conditions, felodipine oxidation product and felodipine
peaks being not less than 2.5. And perform the test with
40 L of the standard solution, as directed under the
above operating conditions, the tailing factor is not
greater than 1.5.
Detection sensitivity: Adjust the detection sensitivity so that the heights of the two peaks in the chromatogram are not less than 20.0% of the full scale.
Phosphate buffer: Dissolve 6.9 g of monobasic sodium phosphate in 400 mL of water, add 8 mL of 1
mol/L phosphoric acid, and add water to make 1000 mL.
tight containers.

solutions of Fenbufen and Fenbufen RS in ethanol (1 in
(2) Determine the infrared spectrum of Fenbufen and
Fenbufen RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) Heavy metalsTake 2.0 g of Fenbufen, add
2 mL of sulfuric acid and carbonize by gentle heating,
proceed according to Method 2 and perform the test.
Fenbufen according to Method 3 and perform the test
(3) Related substancesDissolve 0.1 g of Fenbufen
in 20 mL of acetone and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add acetone
the plate with a mixture of dichloromethane, methanol
spot from the standard solution.
hours).
Fenbufen
O
C
CH 2CH 2CO 2H
C16H14O3: 254.28
Fenbufen, when dried, contains not less than 98.0% and
not more than 101.0% of fenbufen (C16H14O3).
Description
and has a bitter taste.

Fenbufen is sparingly soluble in acetone, slightly soluble
in methanol, in ethanol or in ether and practically insoluble in water.
Fenbufen is a white crystalline powder
Assay Weigh accurately about 0.2 g of Fenbufen, previously dried, dissolve in 100 mL of dehydrated ethanol
and titrate with 0.1 mol/L potassium hydroxide-ethanol

= 25.428 mg of C16H14O3
Fenofibrate
O
Cl
CH3
O
O
H3C
CH3
CH3
C20H21ClO4: 360.83
Fenofibrate contains not less than 98.5% and not more
than 101.0% of fenofibrate (C20H21ClO4), calculated on
the dried basis.
Description Fenofibrate is a white crystalline powder.
Fenofibrate is very soluble in dichloromethane, slightly
soluable in ethanol and practically insoluable in water.
Identification Determine the infrared spectra of Fenofibrate and Fenofibrate RS as directed in the potassium
Melting Point

0.50 g of Fenofibrate in aceton to make exactly 10 mL:
the solution is clear.
(2) AcidDissolve 1.0 g of Fenofibrate in 50 mL of
ethanol, previously neutralized using 0.2 mL of phenolphthalein solution TS: not more than 0.2 mL of 0.1
mol/L sodium hydroxide VS is required to change the
color of the indicator to pink.
(3) ChlorideTo 0.5 g of Fenofibrate, add 25 mL of
water, heat at 50 C for 10 minutes, cool and filter. To 5
mL of the filtrate, add 6 mL of dilute nitric acid TS and
add water to make 50 mL. Prepare the control solution
with 6 mL of dilute nitric acid and 0.30 mL of 0.01
mol/L hydrochloric acid VS, adding water to make 50
(4) Sulfate To 0.5 g of Fenofibrate, add 25 mL of
water, heat at 50 C for 10 minutes, cool and filter. To 10
mL of the filtrate, add 1 mL of dilute hydrochloric acid
TS and add water to make 50 mL. Prepare the control solution with 1 mL of dilute hydrochloric acid and 0.42 mL
of 0.005 mol/L sufuric acid VS, adding water to make 50
(5) Heavy metalsProceed with 1.0 g of Felodipine
(6) Related substancesDisolve 0.100 g of Fenofibrate
in the mobile phase to make exactly 100 mL and use this
solution as the test solution. Separately, dissolve 25.0 mg
of Fenofibrate RS in the mobile phase to make exactly
And separately, dissolve 10.0 mg of fenofibrate RS, 10.0

mg of fenofibrate related substance I RS [(4chlorophenyl)(4-hydroxyphenyl)methanone], 10.0 mg of
of fenofibrate related substance II RS [2-[4-(4-chloro
benzoyl)phenoxy]-2-methylpropanoic acid (fenofibric
acid)] and 20.0 mg of fenofibrate related substance III
RS [1-methylethyl 2-[[2-[4-(4-chlorobenzoyl)phenoxy]2-methylpropanoyl]oxy]2-methylpropanoate] in the mobile phase to make exactly 100 mL. To 1.0 mL of this solution, add the mobile phase to make exactly 100 mL and
use this solution as the standard solution (2). Perform the
solutions as directed under the Liquid Chromatography
according to the following conditions: the areas of the
peaks of fenofibrate related substance I, II and III from
the test solution is not larger than the areas of the corresponding peaks from the standard solution (2) (0.1% each
of fenofibrate related substance I and II; 0.2% of fenofibrate related substance III). The areas of peaks other than
the major peak and peaks of fenofibrate related substance
I, II and III from the test solution is not larger than the
the area of peak of fenofibrate from the standard solution
(2) (0.1%). The total area of all the peaks other than the
major peak from the test solution is not larger than 5
times area of the peak of fenofibrate from the standard
solution (2) (0.5%). Disregard any peak with an area less
than 0.l times that of the peak of fenofibrate from the
(adjust the pH to 2.5 with phosphoric acid) (70 : 30).
System suitability
System performance: Adjust the detection sensitivity with the standard solution (2) so that the heights of
the peaks in the chromatogram are not less than 20.0% of
the full scale. The relative retention times of fenofibrate
related substances I, II, IV, V, VI, VII and III are about
0.34, 0.36, 0.50, 0.65, 0.80, 0.85 and 1.35, respectively
and the resolution between the peaks of fenofibrate related substances I and II is not less than 1.5.
as the retention time of fenofibrate, beginning after the
solvent peak.
Loss on Drying Not more than 0.5% (0.5 g, 60 C, in
vacuum, constant mass).
Assay Weigh acculately about 25 mg each of Fenofibrate and Fenofibrate RS, dissolve in exactly 25 mL of
KP 9 399
the mobile phase and use these solutions as the test solution and the standard solution (1), respectively. Seperately, weigh 10.0 mg of Fenofibrate RS, 10.0 mg of fenofibrate related compound II RS and 20.0 mg of fenofibrate
related compound III RS, dissolve in the mobile phase to
make exactly 100 mL, take 1.0 mL of this solution, add
with 5 L each of the test solution and the standard solution (1) as directed under the Liquid Chromatography
according to the following conditions of the Related substances, and determine AT and AS, of the peak area of fenofibrate of each solution.
Amount (mg) of fenofibrate (C20H21ClO4)
AT
= amount (mg) of Fenofibrate RS A
S
System suitability
times with 5 L of the standard solution (1), as directed
under the above operating conditions, the relative standard deviation of the peak area of fenofibrate is not more
than 1.0%.
Detection sensitivity: Adjust the detection sensitivity so that the heights of the peaks in the chromatogram
are not less than 50.0% of the full scale.
tight containers.
Fenoprofen Calcium Hydrate

O
O
2H2O
H3C
Ca
O
CH3
O
C30H26CaO62H2O: 558.63
Fenoprofen Calcium Hydrate contains not less than
97.0% and not more than 103.0% of fenoprofen calcium
(C30H26CaO6: 522.60), calculated on the anhydous basis.
Description Fenoprofen Calcium Hydrate is white
crystalline powder.
Fenoprofen Calcium Hydrate is slightly soluble in nhexane, in methanol, or in water and practically insoluble
in chloroform.
Identification (1) Mix 1 g of Fenoprofen Calcium Hydrate with 50 mL of acetic acid, heat and filter. Add 2 mL
of ammonium oxalate TS to the filtrate: white precipitate
is formed and it dissolves in 3 mol/L hydrochloric acid
TS.
(2) Determine the infrared spectra of Fenoprofen Calcium Hydrate and of Fenoprofen Calcium Hydrate RS as
Purity (1) CalciumWeigh accurately about 0.75 g of
Fenoprofen Calcium Hydrate, dissolve in ethanol by
heating, if necessary, add ethanol to make exactly 50 mL
and use this solution as the test solution. Put 70 mL of
water, 2 mL of a solution of sodium hydroxide (1 in 10)
and 0.3 g of hydroxynaphtol, mix, add about 1 mL of the
test solution and titrate with 0.05 mol/L disodium ehthylenediaminetetraacetate VS until blue color appears (7.3
to 8.0%, calculated on the anhydrous basis)
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate = 2.044 mg of Ca

(2) Heavy metalsProceed with 1.0 g of Fenoprofen
Calcium Hydrate according to Method 2 and perform the
(3) Related substancesDissolve about 0.2 g of Fenoprofen Calcium Hydrate, accurately weighed, in a
mixture of water-acetonitrile (1 : 1) to make exactly 100
dissolve about 20 mg of Fenoprofen Calcium Hydrate
RS, accurately weighed, in a mixture of wateracetonitrile (1 : 1) to make exactly 100 mL, take 5.0 mL
of this solution, add a mixture of water-acetonitrile (1 :
the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, determine each peak area of the test solution and the standard solution by the automatic integration and calculate the amount of each related compound:
the amount of each related compound is not more than
0.5% and the total amount of related compounds is not
more than 2.0%.
Amount (%) of a related comound
Ai
C
= 10000 W A
S
C : concentration (mg/mL) of Fenoprofen Calcium
Hydrate RS in the standard solution
W : amount (mg) of Fenoprofen Calcium Hydrate
taken to prepare the test solution
Ai : peak area of each related compound obtained
As : peak area of fenoprofen obtained from the standard solution

octylsilanized silica gel for liquid chromatography (5 m
Mobile phase : With the mobile phase A and the mobile B, control the composition stepwise or gradiently as
follows.
Mobile phase A: A mixture of water and acetic acid
(98 : 2)
Mobile phase B: A mixture of acetonitrile and acetic
aicd (98 : 2)
0
0~3
Mobile
phase A
(vol%)
70
70
Mobile
phase B
(vol%)
30
30
3 ~ 41
70 10
30 90
41 ~ 42
10
90
42 ~ 43
10 70
90 30
43 ~ 55
70
30
Time
(minutes)
Elution
condition
Equilibriation
Isocratic
Linear
gradient
Isocratic
Linear
gradient
Reequilibriation

System suitability
System performance: Dissolve 2 mg of 3phenoxybenzoic acid and Fenoprofen Calcium Hydrate
RS in a mixture of water and acetonitrile (1 : 1) to make
100 mL. When the procedure is run with 20 L of this
solution under the above operating conditions, relative
retention times are about 0.89 for 3-phenoxybenzoic acid
and 1.00 for fenoprofen, the resolution between them is
not less than 9.0 and the symmetry factor of fenoprofen
System reproducibility: When the test is repeated 5
above operating conditions, the relative standard deviation of the peak area of fenoprofen is not more than 2.0%.
= 100 C AT
AS
C : Amount (mg) of fenoprofen calcium in Fenoprofen Calcium Hydrate RS, calculated on the anhydrous
basis
Mobile phase : A mixture of acetonitrile, water and
phosphoric acid (50 : 49.6 : 0.4)
System suitability
System performance: Dissolve 5 mg of Fenoprofen
Calcium Hydrate RS and 5 mg of gemfibrozil in a mixture of methanol and water (1 : 1) to make 5 mL. When
above operating conditions, relative retention times are
about 0.5 for fenoprofen and 1.0 for gemfibrozil, the resolution between them is not less than 8 and the column
efficiency determined from the peak of fenoprofen is not
less than 3000 theoretical plates.
above operating conditions, the relative standard deviation of the peak area of fenoprofen is not more than 2.0%.
Fenoterol Hydrobromide
H
HO
Amount (mg) of fenoprofen calcium [(C15H13O3)2Ca]
H
N
H
Water Between 5.0% and 8.0% (1 g, volumetric titration, direct titration)

Assay Weigh accurately about 70 mg each of Fenoprofen Calcium Hydrate and Fenoprofen Calcium Hydrate
RS, add 0.5 mL of 0.5 mol/L hydrochloric acid TS and 2
mL of ethanol, add a mixture of methanol and water (7 :
3) to make exactly 100 mL and use these solutions as the
standard solution as directed under the Liquid Chromatography according to the following conditions, measure
the peak areas of fenopropen obtained from each solutions, AT and AS .
OH
HBr
CH3
OH
OH
C17H21NO4HBr: 384.27
Fenoterol Hydrobromide contains not less than 99.0%
and not more than 101.0% of fenoterol hydrobromide
(C17H21NO4HBr), calculated on the dried basis.
Description Fenoterol Hydrobromide is a white crystalline powder.
Fenoterol Hydrobromide is soluble in ethanol.
Identification (1) Dissolve 10 mg of Fenoterol Hydrobromide in 2 w/v% solution of disodium tetraborate to
make 50 mL. Add 1 mL of 1 w/v% solution of aminopyrazolone, 10 mL of 2 w/v% solution of potassium ferri-
KP 9 401
cyanide and 10 mL of dichloromethane, mix and allow to
stand: a reddish-brown color develops in the lower layer.
(2) Prepare 0.037 w/v% solutions in diluted hydrochloric acid (1 in 10000) of Fenoterol Hydrobromide and
Fenoterol Hydrobromide RS, respectively. Determine the
(3) Determine the infrared spectra of Fenoterol Hydrobromide and Fenoterol Hydrobromide RS as directed
in potassium bromide disk method under the Infrared absorption Spectrophotometry: both spectra exhibit similar
(4) Dissolve 10 mg each of Fenoterol Hydrobromide
and Fenoterol Hydrobromide RS in ethanol to make 10
standard solution, respectively. Perform the test with
chromatography. Develop the plate with a mixture of methanol, water and ammonia solution (28) (90 : 10 : 1.5) to
a distance of about 15 cm and air-dry the plate. Spray
evenly 1 w/v% potassium permanganate solution on the
plate: the principal spot from the test solution shows the
same Rf value as the principal spot from the standard solution.
(5) A solution of Fenoterol Hydrobromide (1 in 100)
responds to the Qualitative Test (1) for bromides.
pH Dissolve 2.0 g of Fenoterol Hydrobromide in water
to make exactly 50: the pH of this solution is between
4.2 and 5.2.
g of Fenoterol Hydrobomide in water to make exactly 50
mL: the solution is clear and colorless.
(2) IronProceed with 1.0 g of Fenoterol Hydrobomide according to Method 3 and perform the test according to Method A. Prepare the control solution with 0.5
mL of standard iron solution (not more than 5 ppm).
(3) PhenoneDissolve 2.0 g of Fenoterol Hydrobomide in water to make exactly 50 mL and Determine
the absorbance of this solution at 330 nm, as directed under the Ultraviolet-visible Spectrophotometry: the absorbance is not more than 0.42 (not more than 0.2%)
(4) IsomerDissolve 20 mg each of Fenoterol Hydrobromide and Fenoterol Hydrobromide RS in water to
with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the peak
heights, HT and HS of peak eluted right after the principal
peak, for the test solution and the standard solution and
calculate the amount of isomer: the amount of isomer is
not more than 4.0%.
Amount(%) of isomer = amount(%) of isomer

labeled on Reference Standard H T
HS
(5 to 10 m in particle diameter).
Mobile phase : Mix 10 mL of 0.9 w/v% potassium
dihydrogen phosphate and 690 mL of 2.5 w/v% sodim
hydrogen phosphate dodecahydrate and add phosphoric
acid to adjust pH to 8.5, add 300 mL of methanol and
mix.
Flow rate: 1.0 mL/minute. Adjust the flow rate so
that the retention time of the principal peak is not more
than 20 minutes.
System suitability
conditions, adjust the sensitivity so that the height of
peak eluted right after the principal peak is not less than
10% of the full scale and the height of valley between the
principal peak and the isomer peak is not more than 4%
of the full scale.
Loss on Drying Not more than 0.5% (0.5 g, 105 C,
constant mass).
Assay Weigh accurately about 0.6 g of Fenoterol Hydrobromide, dissolve in 50 mL of water, add 5 mL of dilute nitric acid TS and 25 mL of 0.1 mol/L silver nitrate
VS, shake and titrate with 0.1 mol/L ammonium thiocyanate VS until an orange color is obtained (indicator: 2
mL of ferric ammonium sulfate solution TS). Perform a

= 38.48 mg of C17H21NO4
Fentanyl Citrate
O
C
CH2CH2
CH2CH3
CH2CO2H
HO
CO2H
CH2CO2H
C22H28N2OC6H8O7: 528.60
Fentanyl Citrate contains not less than 98.0% and not

less than 101.0% of fentanyl citrate (C22H28N2OC6H8O7), calculated on the dried basis.
Description Fentanyl Citrate is a white crystal or crystalline powder.
Fentanyl Citrate is freely soluble in methanol or in glacial acetic acid, sparingly soluble in water or in ethanol
and very slightly soluble in ether.
Identification (1) Dissolve 50 mg each of Fentanyl Citrate and Fentanyl Citrate RS in 10 mL of 0.1 mol/L hydrochloric acid TS and ethanol to make 100 mL and determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Fentanyl Citrate
and Fentanyl Citrate RS, previously dried, as directed in
(3) A solution of Fentanyl Citrate (1 in 100) responds
to the Qualitative Tests (1) for citrate.
pH Dissolve 0.10 g of Fentanyl Citrate in 10 mL of
Purity (1) Heavy metalsProceed with 0.5 g of Fentanyl Citrate according to Method 2 and perform the test.
(2) Related substancesDissolve 0.10 g of Fentanyl
Citrate in 5 mL of methanol and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 100 mL and use this solution as
of n-butanol, water and glacial acetic acid (3 : 1 : 1) to a
evenly Dragendorffs TS for spraying on the plate: the
silica gel, 60 C, 2 hours).
Assay Weigh accurately about 75 mg of Fentanyl Citrate, dissolve in 50 mL of glacial acetic acid and titrate
with 0.02 mol/L perchloric acid VS (potentiometric titra-
tion, Endpoint Detection Method in Titrimetry). Perform

= 10.572 mg of C22H28N2OC6H8O7
tight containers.
Fenticonazole Nitrate
Cl
Cl
H
O
HNO3
N
S
and enantiomer
C24H20Cl2N2OSHNO3: 518.41
Fenticonazole Nitrate contains not less than 99.0% and
not more than 101.0% of fenticonazole nitrate
(C24H20Cl2N2OSHNO3), calculated on the dried basis.
Description Fenticonazole Nitrate is a white powder.
Fenticonazole Nitrate is freely soluble in methanol and in
dimethylformamide, sparingly soluble in ethanol, and
solutions of Fenticonazole Nitrate and Fenticonazole Nitrate RS in ethanol (1 in 50000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Determine the infrared spectra of Fenticonazole
Nitrate and Fenticonazole Nitrate RS, as directed in the
(3) Weigh a portion of Fenticonazole Nitrate equivalent to about 1 mg of nitrate ion, mix with a mixture of
0.1 mL of nitrobenzene and 0.2 mL of sulfuric acid,
stand for 5 minutes, cool in ice-water, add gently 5 mL of
water while stirring. Add 5 mL of 10 mol/L sodium hydroxide TS and 5 mL of of aceton, shake and stand: a
color of deep violet develops in the upper layer.
Meting Point Between 134 C and 137 C
Purity (1) TolueneWeigh exactly 0.2 g of Fenticonazole Nitrate in a 10-mL vial, add exactly 5 mL of water
to disperse and use this solution as the test solution, Separately, add 4.0 mg of toluene to water to make 1000 mL.
KP 9 403
Take 5 mL of this solution to a 10-mL vial and use it as
the standard solution. Perform the test with the test solution and the standard solution as directed in the standard
addition method under the Gas Chromatography according to the following operating conditions. Use a headspace sample introduction device to measure the amount
of toluene by the standard addition method: the amount
of toluene is not more than 100 ppm.
Column: A column, about 0.32 mm in inside diameter and about 25 m in length, coated with
poly(cyanopropyl)(7)phenyl(7)methyl(86)siloxane
for
gas chromatography (1.2 m in film thickness).
Inlet temperature: 180 C.
Detector temperature: 220 C.
Split ratio: about 1 : 25
Column head pressure: 40 kPa.
Injection volume: Maintain each solution at 90 C for
1 hour and transfer 1 mL of the vapor phase onto the column.
(2) Related substancesDissolve about 25 mg of Fenticonazole Nitrate, accurately weighed, in the mobile
the mobile phase to make exactly 200 mL, and use this
solution as the standard solution (1). Pipet exactly 10 mL
of the standard solution (1), add the mobile phase to
make exactly 25 mL, and use this solution as the standard solution (2). Pipet exactly 1 mL of the standard solution (1), add the mobile phase to make exactly 10 mL,
exactly 5 mL of the test solution, add 5.0 mg of fenticonazole related substance I RS {(RS)-1-[2-(2,4dichlorophenyl)-2-hydroxyethyl]-3-[4-(phenylsulphanyl)
benzyl]imidazolium nitrate} add the mobile phase to
make exactly 100 mL, pipet exactly 2 mL of this solution,
add the mobile phase to make exactly 10 mL and use this
with 10 L each of the test solution and the standard solution (1) as directed under the Gas Chromatography according to the following operating conditions and determine the area of each peak by the automatic integration
method: the area of any peak except the principal peak
and the nitrate ion peak (which correspond to the dead
volume of the column) obtained from the test solution is
not greater than the area of the principal peak obtained
from the standard solution (2) (0.2%) and the sum of of
the areas of such peaks is not greater than the area of the
principal peak obtained from the standard solution (1)
(0.5%). Disregard any peak with an area less than that of
the principal peak from the standard solution (3).
Detector : An ultraviolet absorption photometer (wa-
velength: 210 nm).

Column : A stainless steel column, about 4 mm in inside diameter and about 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5
Mobile phase : A mixture of acetonitrilethe and
phosphate buffer (70 : 30)
System suitability
The procedure is run with 10 L of the standard
solution (2) under the above operating conditions, and
adjust the sensitivity of the system so that the height of
fenticonazole peak is not less than 10% of the full scale
of the recorder. When the procedure is run with 10 L
each of the standard solution (3) and the standard solution (4) under the above operating conditions, the resolution between the peaks of fenticonazole related substance
I and fenticonazole is not less than 2, and the signal-tonoise ratio of the chromatogram obtained with the standard solution (3) is not less than 5.
Phosphate bufferDissolve 3.4 g of potassium dihydrogen phosphare in 900 mL of water, adjusting to pH
3.0 with phosphoric acid, and add water to make 1000
mL.
60 C, constant mass).
Assay Weigh accurately about 0.45 g of Fenticonazole
Nitrate, dissolve in 50 mL of a mixture of methyl ethyl
ketone and glacial acetic acid (1 : 1) and titrate with 0.1

= 51.84 mg of C24H20Cl2N2OSHNO3

Ferrous Fumarate
HC
O
C
O
CH
O
Fe
C4H2FeO4: 169.91
Ferrous Fumarate, when dried, contains not less than
97.0% and not more than 101.0% of ferrous fumarate
(C4H2FeO4).
Description Ferrous Fumarate is a reddish-orange to

reddish-brown powder and is odorless.
Ferrous Fumarate is slightly soluble in water and very
slightly soluble in ethanol.
The solubility of Ferrous Fumarate in dilute hydrochloric
acid is decreased by liberation of fumaric acid.
Identification (1) To 1.5 g of Ferrous Fumarate, add
25 mL of diluted hydrochloric acid (1 in 2), dilute with
water to make 50 mL, heat to obtain complete solution,
then cool, filter on a glass filter, wash the precipitate with
diluted hydrochloric acid (3 in 100) and dry the precipitate at 105 C. Determine the infrared absorption spectra
of the dried precipitate and Fumaric Acid RS, as directed
(2) The filtrate of (1) responds to the Qualitative
Tests for iron.
Purity (1) SulfateTransfer 1.0 g of Ferrous Fumarate to a beaker, add 100 mL of water and heat on a water-bath, adding hydrochloric acid drop-wise until complete solution is obtained (about 2 mL of the acid is required). Filter the solution, if necessary, and dilute the
filtrate with water to make 100 mL. Heat this solution to
boiling, add 10 mL of barium chloride TS, warm on a
water-bath for 2 hours, cover and allow to stand for 16
hours. If crystals of ferrous fumarate form, warm the solution on a water-bath to dissolve them. Filter the solution through weighing filter paper, add ammonium sulfide TS to the filtrate, wash the residue with hot water
until no more black precipitate is produced and transfer
the paper containing the residue to a previously tared
crucible. Char the paper, without burning and ignite the
crucible and its contents at 600 C to a constant mass:
each mg of residue is equivalent to 0.412 mg of sulfate
(SO4) (not more than 0.2%).
(2) ArsenicTransfer about 2.0 g of Ferrous Fumarate to a beaker and add 10 mL of water and 10 mL of
sulfuric acid. Warm to precipitate fumaric acid completely, cool, add 20 mL of water and filter into a 50 mL volumetric flask. Wash the precipitate with water, add the
washings to the flask, add water to to the mark. Perform
the test with 25 mL of this solution. Prepare the control
solution with 3.0 mL of standard arsenic solution (not
more than 3 ppm).
(3) Ferric ionTransfer about 2.0 g of Ferrous Fumarate, accurately weighed, to a glass-stoppered, Erlenmyer flask, add 25 mL of water and 4 mL of hydrochloric acid and heat on a hot plate until complete solution is
obtained. Stopper the flask and cool to room temperature.
Add 3 g of potassium iodide, stopper the flask, swirl to
mix and allow to stand in the dark for 5 minutes. Remove the stopper, add 75 mL of water and titrate with 0.1
TS). Not more than 7.16 mL of 0.1 mol/L sodium thiosulfate is consumed (not more than 2.0%).
(4) MercuryPerform the test with light-resistant
container. Dissolve about 1 g of Ferrous Fumarate, accu-
rately weighed, in 30 mL of diluted nitric acid (1 in 10),

by heating on a water-bath. Cool quickly by immersion
in an ice-bath and filter through a filter (G4), previously
washed with diluted nitric acid (1 in 10) and water. To
the filtrate, add 20 mL of sodium citrate solution (1 in 4)
and 1 mL of hydroxylamine hydrochloride TS and use
this solution as the test solution. Separately, prepare a
control solution consisting of 3.0 mL of standard mercury solution, 30 mL of diluted nitric acid (1 in 10), 5
mL of sodium citrate solution (1 in 4) and 1 mL of hydroxylamine hydrochloride TS. To the control solution,
add ammonium hydroxide TS to adjust to a pH of 1.8,
add sulfuric acid to the test solution to adjust to a pH of
1.8 and transfer to a separator, respectively. Perform the
test with the test solution and the control solution as follows. Extract with two 5 mL volumes of dithizone solution for extraction and 5 mL of chloroform and transfer
the chloroform extracts to a second separator. Add 10 mL
of diluted hydrochloric acid (1 in 2), shake to mix, allow
the layers to separate and discard the chloroform layer.
Wash the acid extract with 3 mL of chloroform and discard the washing. Add 0.1 mL of disodium ethylenediamine tetraacetate solution (1 in 50) and 2 mL of 6 mol/L
acetic acid, mix and add slowly 5 mL of ammonia TS.
Stopper the separator and cool under cold running water.
Remove the stopper and pour the contents into a beaker.
Adjust the test solution and the control solution to a pH
of 1.8 in the same manner as before and return the solution to its separator, respectively. Add 5.0 mL of diluted
dithizone solution for extraction, shake vigorously and
allow the layers to separate. At this point, compare the
colors observed in the chloroform layers of the two solutions that have been treated in parallel: the color observed by the test solution is not more intense than that
observed by the control solution (not more than 3 ppm).
Mercury stock solutionTransfer 135.4 mg of mercuric chloride to a volumetric flask, dissolve in 0.5 mol/L
sulfuric acid and add 0.5 mol/L sulfuric acid to make 100
mL and mix. This solution contains 0.1 g of mercury
(Hg) in 100 mL.
Mercury standard solutionTransfer 1.0 mL of mercury stock solution to a volumetric flask before use and
add 0.5 mol/L sulfuric acid to make 1000 mL and mix.
This solution contains 1 g of mercury (Hg) in 1 mL.
Diluted dithizone solution for extractionDilute 5
mL of dithizone solution for extraction with 25 mL of
chloroform before use.
(5) LeadAdd 1.0 g of Ferrous Fumarate to a beaker,
add 6 mL of nitric acid and 10 mL of perchloric acid,
cover with a watch glass and heat until complete dryness.
Cool, dissolve the residue in 10 mL of 9 mol/L hydrochloric acid and transfer with the aid of about 10 mL
of water to a volumetric flask. Add 20 mL of ascorbic acid-sodium iodide solution and 5.0 mL of trioctylphosphine oxide solution, shake for 30 seconds and allow to
KP 9 405
separate. Add water to bring the organic solvent layer into the neck of the flask, shake again and allow to separate. Use the organic solvent layer as the test solution.
Separately, transfer 5.0 mL of lead stock solution and
add water to make exactly 100 mL. Transfer exactly 2
mL of the resulting solution to a beaker. To this beaker
and to a second empty beaker, add 6 mL of nitric acid
and 10 mL of perchloric acid and evaporate to dryness.
Cool, dissolve the residue in 10 mL of 9 mol/L hydrochloric acid and transfer with the aid of about 10 mL of water to a volumetric flask. To each flask, add 20 mL of ascorbic acid-sodium iodide solution and 5.0 mL of trioctylphosphine oxide solution, shake for 30 seconds and allow to separate. Add water to bring the organic solvent
layer into the neck of each flask, shake again and allow
to separate. Use the organic solvent layers as the standard
solution (2.0 g/mL) and the blank solution, respectively.
Determine the absorbances of the blank solution, the test
Atomic Absorption Spectrophotometer according to the
following conditions: the absorbance of the test solution
doses not exceed that of the standard solution (not more
than 0.001%). But, using 4-methyl-2-pentanone to set the
instrument to zero, the absorbance of the blank solution
is not greater than 20% of the difference between the absorbance of the standard preparation and that of the blank
solution.
Lamp: A lead hollow-cathode lamp.
Trioctylphosphine oxide solutionDissolve 5.0 g of
trioctylphosphine oxide in 4-methyl-2-pentanone to
make 100 mL.
hours).
Assay Transfer about 0.5 g of Ferrous Fumarate, accurately weighed, to an Erlenmyer flask, add 25 mL of diluted hydrochloric acid (2 in 5) and heat to boiling. Add
a solution of 5.6 g of stannous chloride in 50 mL of diluted hydrochloric acid (3 in 10) until yellow color disappears, then add 2 drops in excess. Cool the solution in
an ice-bath to room temperature, add 10 mL of mercuric
chloride solution (1 in 20) and allow to stand for 5 minutes. Add 200 mL of water, 25 mL of diluted sulfuric
acid (1 in 2) and 4 mL of phosphoric acid and then titrate
with 0.1 mol/L ceric ammonium sulfate VS (indicator: ophenanthroline TS). Perform a blank determination and
Each mL of 0.1 mol/L ceric ammonium sulfate VS

= 16.990 mg of C4H2FeO4
Ferrous Fumarate Tablets

Ferrous Fumarate Tablets contain not less than 95.0%
and not more than 110.0% of the labeled amount of ferrous fumarate (C4H2FeO4: 169.90).
Method of Preparation Prepared as directed under
Tablets, with Ferrous Fumarate.
Identification Shake well a portion of powdered Ferrous Fumarate Tablets, equivalent to 1 g of Ferrous Fumarate according to the labeled amount, with 25 mL of diluted hydrochloric acid (1 in 2) and add 25 mL of water.
Boil the solution for a few minutes, cool and filter: the
filtrate responds to the Qualitative Tests for iron.
Dissolution Test Perform the test with 1 tablet of Ferrous Fumarate Tablets at 75 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL out of 1000 mL solution of 5 g of lauryl sodium
sulfate in 0.1 mol/L hydrochloric acid. Take the dissolved solution at 45 minutes after starting the test and
filter. Discard the first 10 mL of the filtrate and use the
subsequent filtrate as the test solution. Separately, dry
and weigh accurately a portion of Ferrous Fumarate RS,
dissolve in the same solvent to make a constant concentration and use this solution as the standard solution. Determine the absorbances of the test solution and the standard solution at 248.3 nm as directed under the Ultraviolet-visible Spectrophotometry using the dissolution solution as the blank.
The dissolution rate of Ferrous Fumarate Tablets in

45 minutes is not less than 75%.
Ferrous Fumarate Tablets, transfer an accurately weighed
portion of the powder, equivalent to about 0.5 g of ferrous fumarate (C4H2FeO4), to a beaker and add 25 mL of
water, 25 mL of nitric acid and 7.5 mL of perchloric acid.
Cover with a watch glass and heat until strong fumes are
produced. Cool, rinse the watch glass and the sides of the
beaker with water and then evaporate in a hood to neardryness. Wash down the watch glass and the sides of the
beaker with hydrochloric acid 2 mL and then with a
small volume of water. Warm slightly, if necessary, to
dissolve the residue, transfer to a glass-stoppered Erlenmyer flask, wash the beaker with 2 mL of hydrochloric
acid and transfer the washing to the flask. Completely
wash the beaker with 20 to 25 mL of water for the transfer, add 4 g of potassium iodide to the flask, stopper and
allow to stand in the dark for 5 minutes. Add 75 mL of
water and titrate with 0.1 mol/L sodium thiosulfate VS
(indicator: 3 mL of starch TS, add it as the endpoint is
approached.)

= 16.990 mg of C4H2FeO4
Ferrous Gluconate Hydrate

HOH2C
OH OH
OH
OH
CO2
2+
Fe
2H2O
C12H22FeO142H2O: 482.17
Ferrous Gluconate Hydrate, when dried, contains not less
than 97.0% and not more than 102.0% of ferrous gluconate (C12H22FeO14: 446.14).
Description Ferrous Gluconate Hydrate is a yellowish
gray or pale yellow green fine powder or granule and has
a slight odor like sulfur-burning.
One gram of Ferrous Gluconate Hydrate is soluble in 10
mL of hot water and very slightly soluble in ethanol.
An aqueous solution of ferrous gluconate (1 in 20) is
acidic.
Identification (1) Dissolve about 10 mg of Ferrous
Gluconate Hydrate in 10 mL of water, if necessary, heat
on a water-bath at 60 o C and use this solution as the test
solution. Separately, dissolve 10 mg of Ferrous Gluconate Hydrate RS in 10 mL of water and use this solution
as the standard solution. Apply separately 5 L volume
of the test solution and the standard solution in a suitable
thin-layer chromatographic plate coated with chromatographic silica gel. Develop the chromatogram in a solvent system consisting of a mixture of ethanol, water,
strong ammonium hydroxide solution and ethyl acetate
(50 : 30 : 10 : 10) until the solvent front has moved about
15 cm of the plate. Remove the plate from the chamber
and dry at 110 o C for 20 minutes. Allow to cool, spray
with a spray reagent prepared as follow; dissolve 2.5 g of
ammonium molibdenate in about 50 mL of 1 mol/L sulfuric acid TS in a volumetric flask, add 1.0 g of ceric sulfate, swirl to dissolve, add 1 mol/L sulfuric acid TS to
make 100 mL and mix. Heat the plate at 110 o C for
about 10 minutes: the color, size and Rf value of the
principal spot obtained from the test solution should be
the same as those obtained from the standard solution.
(2) Addition of potassium ferricyanide TS to an
aqueous solution of Ferrous Gluconate Hydrate (1 in
200): dark blue precipitation is produced.
Purity (1) ChlorideProceed with 1.0 g of Ferrouse
Gluconate Hydrate. Prepare the control solution with 1.0
0.07%).
(2) SulfateProceed with 1.0 g of Ferrous Gluconate Hydrate. Prepare the control solution with 1.0 mL of
(3) Oxalic acidDissolve 1.0 g of Ferrous Gluconate Hydrate in 10 mL of water, add 2 mL of hydrochloric acid and transfer to a separator. Extract successively
with 50 mL and 20 mL volumes of ether. Combine the
ether extracts, add 10 mL of water and evaporate the ether on a steam-bath. Add 1 drop of 6 mol/L acetic acid
and 1 mL of calcium acetate solution (1 in 20): no turbidity is produced within 5 minutes.
(4) LeadAdd 1.0 g of Ferrous Gluconate Hydrate,
10 mL of 9 mol/L hydrochloric acid TS, about 10 mL of
water, 20 mL of ascorbic acid, sodium iodide solution
and 5.0 mL of triocytylphosphine oxide mythyl isobytylketone solution to a volumetric flask, shake for 30
seconds and allow to separate. Add water into the neck of
the flask, shake again and allow to separate. The organic
solvent layer collected is used as the test solution. Separately, pipet 5.0 mL of lead nitrate standard stock solution into a volumetric flask, dilute with water to make
100 mL, pipet 2.0 mL of the solution to a volumetric
flask and then prepare the standard solution, as directed
under the test solution. Determine the absorbances of the
test solution and the standard solution according to the
following conditions, as directed under the Ultravioletvisible Spectrophotometry: the absorbance of the solution obtained from the test solution is not greater than
Gas: Flammable Acetylene gas.
Delayed gas: Air.
Lamp: Lead hollow-cathode lamp.
(5) ArsenicWeigh 1.0 g of Ferrous Gluconate Hydrate in a round-bottom flask and add 40 mL of 4.5
mol/L sulfuric acid and 2 mL of potassium bromide solution (3 in 10). Immediately collect to a suitable distillation apparatus having a reservoir with a water jacket,
cooled with circulating icewater and heat to dissolve the
test specimen. Prepare 25 mL of distillate as the test solution and perform the test (not more than 3 ppm).
(6) Ferric ionDissolve about 5 g of Ferrous Gluconate Hydrate, exactly weighed, in a mixture of 100 mL
of water and 10 mL of hydrochloric acid and add 3 g of
potassium iodide. Shake and allow to stand in the dark
place for 5 minutes. Titrate any liberated iodine with 0.1
TS). Perform a blank determination and make any necessary correction (not more than 2.0%).
= 5.585 mg of Fe+3
(7) Reducing sugarsDissolve about 500 mg of
Ferrous Gluconate Hydrate in 10 mL of water, warm and
render alkaline with 1 mL of 6 mol/L ammonium hydroxide TS. Pass hydrogen sulfide gas into the solution
to precipitate the iron and allow to stand for 30 minutes.
KP 9 407
Filter and wash the precipitate with two successive 5 mL
volumes of water. Acidify the combined filtrate and
washings with hydrochloric acid and add 2 mL of dilute
hydrochloric acid. Boil the solution until the vapors no
longer darken lead acetate paper and continue to boil, if
necessary, until concentrated to be about 10 mL. Cool,
add 5 mL of sodium carbonate TS and 20 mL of water,
filter and add water to make 100 mL. Take 5 mL of the
filtrate, add 2 mL of Fehling TS and boil for 1 minute: no
red precipitate is produced within 1 minute.
Loss on Drying Between 6.5% and 10.0% (1 g, 105 C,
16 hours).
Assay Dissolve about 1.5 g of Ferrous Gluconate Hydrate, accurately weighed, in a mixture of 75 mL of water and 15 mL of dilute sulfuric acid in a cornical-flask.
Add 250 mg of zinc powder, close the flask with a stopper containing a Bunsen valve and allow to stand at room
temperature for 20 minutes or until the solution becomes
colorless. Filter the solution through a filtering crucible
containing an asbestos mat coated with a thin-layer of
zinc dust and wash the crucible and contents with 10 mL
of dilute sulfuric acid, followed by 10 mL of water. Add
o-phenanthroline TS and titrate the filtrate in the suction
flask immediately with 0.1 mol/L ammonium ceric sulfate VS. Perform a blank determination and make any
Each mL of 0.1 mol/L ammonium ceric sulfate VS

= 44.61 mg of C12H22FeO14
solution 80 minutes after the start of the test, filter

through a membrane filter and use the filtrate solution as
the test solution. If necessary, dilute the test solution as a
suitable concentration using the test solution. Separately,
weigh accurately a portion of Ferrous Gluconate Hydrate
RS, add the test solution to dissolve and prepare the
standard solution containing the same iron concentration
as the test solution. Determine the absorbances of the test
solution and the standard solution according to the following conditions, as directed under the Ultravioletvisible Spectrophotometry. Calculate the content of iron
using the calibration curve obtained from the absorbance
of standard solution.
Lamp: Iron hollow-cathode lamp.
The dissolution rate of Ferrous Gluconate Tablets in
80 minutes is not less than 80.0%.
Assay Weigh and finely powder not less than 20 Ferrous Gluconate Tablets. Weigh accurately a portion of the
powder, equivalent to about 1.5 g of Ferrous Gluconate
Hydrate and dissolve in a mixture of 75 mL of water and
15 mL of dilute sulfuric acid in a cornical-flask. Proceed
as directed in the Assay under Ferrous Gluconate Hydrate.
Each mL of 0.1 mol/L ammonium ceric sulfate VS

= 48.22 mg of C12H22FeO14.2H2O
Ferrous Gluconate Tablets

C12H22FeO142 H2O: 482.17
Ferrous Gluconate Tablets contain not less than 93.0%
and not more than 107.0% of ferrous gluconate hydrate
(C12H22FeO142 H2O: 482.17).
Method of Preparation Prepare as directed under Tablets, with Ferrous Gluconate Hydrate.
Identification Take a portion of powdered Ferrous
Gluconate Tablets, equivalent to about 1 g of Ferrous
Gluconate Hydrate according to the labeled amount, add
100 mL of water and filter: the suitable volume of the filtrate is diluted with water, to a designated concentration.
Perform the test with the solution as directed in the Identification under Ferrous Gluconate Hydrate.
Dissolution Test Perform the test with 1 tablet of Ferrous Gluconate Tablets at 150 revolutions per minute according to Method 1 under the Dissolution Test, using
900 mL of artificial gastric solution. Take the dissolved
Ferrous Sulfate Hydrate

FeSO47H2O: 278.02
Ferrous Sulfate Hydrate contains not less than 98.0% and
not more than 104.0% of ferrous sulfate (FeSO47H2O).
Description Ferrous Sulfate Hydrate is a pale green
crystal or crystalline powder, is odorless and has an astringent taste.
Ferrous Sulfate Hydrate is freely soluble in water and
practically insoluble in ethanol.
Ferrous Sulfate Hydrate is efflorescent in dry air and its
crytalline surface becomes yellowish brown in moist air.
Identification A solution of Ferrous Sulfate Hydrate (1
in 10) responds to the Qualitative Tests for ferrous salt
and for sulfate.
Purity (1) Clarity of solutionDissolve 1.0 g of Ferrous Sulfate Hydrate in 20 mL of water and 1 mL of di-

lute sulfuric acid: the solution is clear.
(2) AcidTake 5.0 g of powdered Ferrous Sulfate
Hydrate, add 50 mL of ethanol, shake well for 2 minutes
and filter the mixture. To 25 mL of the filtrate, add 50
mL of water, 3 drops of bromothymol blue TS and 0.5
mL of dilute sodium hydroxide TS: a blue color is observed.
(3) MercuryPerform the test with light-resistant
container. Dissolve about 1 g of Ferrous Sulfate Hydrate,
accurately weighed, in 30 mL of diluted nitric acid (1 in
10), by heating on a water-bath. Cool quickly by immersion in an ice-bath and filter through a filter (G4), previously washed with diluted nitric acid (1 in 10) and water. To the filtrate, add 20 mL of sodium citrate solution
(1 in 4) and 1 mL of hydroxylamine hydrochloride TS
and use this solution as the test solution. Separately, prepare a control solution consisting of 3.0 mL of standard
mercury solution, 30 mL of diluted nitric acid (1 in 10), 5
mL of sodium citrate solution (1 in 4) and 1 mL of hydroxylamine hydrochloride TS. To the control solution,
add ammonium hydroxide TS to adjust to a pH of 1.8,
add sulfuric acid to the test solution to adjust to a pH of
1.8 and transfer to a separator, respectively. Perform the
test with the test solution and the control solution as follows. Extract with two 5 mL volumes of dithizone solution for extraction and 5 mL of chloroform and transfer
the chloroform extracts to a second separator. Add 10 mL
of diluted hydrochloric acid (1 in 2), shake to mix, allow
the layers to separate and discard the chloroform layer.
Wash the acid extract with 3 mL of chloroform and discard the washing. Add 0.1 mL of disodium ethylenediamine tetraacetate solution (1 in 50) and 2 mL of 6 mol/L
acetic acid, mix and add slowly 5 mL of ammonia TS.
Stopper the separator and cool under cold running water.
Remove the stopper and pour the contents into a beaker.
Adjust the test solution and the control solution to a pH
of 1.8 in the same manner as before and return the solution to its separator, respectively. Add 5.0 mL of diluted
dithizone solution for extraction, shake vigorously and
allow the layers to separate. At this point, compare the
colors observed in the chloroform layers of the two solutions that have been treated in parallel: the color observed by the test solution is not more intense than that
observed by the control solution (not more than 3 ppm).
Mercury stock solutionTransfer 135.4 mg of mercuric chloride to a volumetric flask, dissolve in 0.5 mol/L
sulfuric acid and add 0.5 mol/L sulfuric acid to make 100
mL and mix. This solution contains 0.1 g of mercury
(Hg) in 100 mL.
(5) LeadTake 1.0 g of Ferrous Sulfate Hydrate in a

50 mL volumetric beaker, add 10 mL of 9 mol/L hydrochloric acid about 10 mL of water, 20 mL of ascorbic
acid-sodium iodide solution and 5 mL of trioctylphosphine oxide solution in methylisobutylketone (5 in 100),
shake for 30 seconds and allow to separate. Add water to
bring the organic solvent layer into the neck of the flask,
shake again and allow to separate. Use the organic solvent layer as the test solution. Separately, transfer exactly
5 mL of lead stock solution and add water to make exactly 100 mL. Transfer exactly 2 mL of the resulting solution to a 50 mL volumetric flask and proceed as the test
solution and use this soluteon as the standard solution.
Determine the absorbances of the the test solution and
the standard solution as directed under the Atomic Absorption Spectrophotometer according to the following
conditions: the absorbance of the test solution doses not
exceed that of the standard solution.
Lamp: A lead hollow-cathode lamp.
(5) ArsenicTake 1.0 g of Ferrous Sulfate Hydrate
in 100 mL round-bottomed flask, add 40 mL of 4.5
mol/L sulfuric acid and 2 mL of potassium bromide solution (1 in 10) and connect the flask to a distillation apparatus with ice-water cooled condenser. Perform the test
using 25 mL of the distillate as the test solution (not
more than 3 ppm).
Assay Dissolve about 0.5 g of Ferrous Sulfate Hydrate,
accurately weighed, in a mixture of 20 mL of 1 mol/L
sulfuric acid TS and 80 mL of freshly boiled and cooled
water and then titrate with 0.1 mol/L ceric ammonium
sulfate VS (indicator: ortho-phenanthroline TS). Perform

= 27.802 mg of FeSO47H2O
Ferrous Sulfate Tablets

Ferrous Sulfate Tablets contain not less than 95.0% and
not more than 110.0% of the labeled amount of ferrous
sulfate hydrate (FeSO47H2O: 278.02).
Mercury standard solutionTransfer 1.0 mL of mercury stock solution to a volumetric flask before use and
add 0.5 mol/L sulfuric acid to make 1000 mL and mix.
This solution contains 1 g of mercury (Hg) in 1 mL.
Method of Preparation Prepared as directed under

Tablets, with Ferrous Sulfate.
Diluted dithizone solution for extractionDilute 5

mL of dithizone solution for extraction with 25 mL of
chloroform before use.
Identification Weigh a portion of finely powdered

Ferrous Sulfate Tablets, equivalent to 0.25 g of Ferrous
Sulfate according to the labeled amount, add water, aci-
KP 9 409
dify with hydrochloride and add water again to make 25
mL: the solution responds to the Qualitative Tests for
ferrous salts and for sulfate.
Finasteride
O
Dissolution Test Perform the test with 1 tablet of Ferrous Sulfate Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of 0.1 mol/L hydrochloric acid. Take the dissolved
solution at 45 minutes after starting the test and filter.
Discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, dry and
weigh accurately a portion of ferrous sulfate RS, dissolve
in the same solvent to make a constant concentration and
absorbances of the test solution and the standard solution
as directed under the Atomic Absorption Spectrophotometry.

Lamp: A iron hollow-cathode lamp.
The dissolution rate of Ferrous Sulfate Tablets in 45
minutes is not less than 75% (Q).
Ferrous Sulfate Tablets, weigh accurately a portion of the
powder, equivalent to about 0.5 g of Ferrous Sulfate (FeSO47H2O), dissolve in a mixture of 20 mL of 1 mol/L
sulfuric acid and 80 mL of freshly boiled and cooled water. Filter the solution as soon as all soluble ingredients in
the tablets are dissolved and wash the residue in the container and the filter with small portions of a mixture of
20 mL of 1 mol/L sulfuric acid and 80 mL of freshly
boiled and cooled water. Immediately titrate the combined filtrate and washings with 0.1 mol/L ceric ammonium sulfate VS (indicator: ortho-phenanthroline TS).
correction.

= 27.802 mg of FeSO47H2O
CH3
H
N
H
CH3
CH3
CH3
CH3
H
N
C23H36N2O2 : 372.54
Finasteride contains not less than 98.5% and not more
than 101.0% of finasterid (C23H36N2O2), calculated on
Description Finasteride is a white to grayish white,
crystalline powder.
Finateride is freely soluble in ethanol, or in chloroform,
and very slightly soluble in water.
Melting pointabout 257 C
Finateride and Finasteride RS, as directed in the paste
same wavenumbers.
(2) The retention time of the principal peak obtained
from the test solution under Assay is equal to that of the
principal peak obtained from the standard solution.
Specific Optical Rotation [] 25
405 nm : Between -56.0
and -60.0 (0.1 g, methanol, 10 mL, 100 mm)
Purity (1) Heavy metalsProceed with 1.0 g of Finasteride according to Method 2 and perform the test. Prepare the control solution with 1.0 mL of standard lead solution (not more than 10 ppm).
(2) Related substancesDissolve about 0.1 g of Finasteride, accurately weighed, in a mixture of water and
acetonitrile (1 : 1) to make exactly 100 mL and use this
solution as the test solution. Perform the test with 15 L
of the test solution as directed under the Liquid Chromatography according to the following operating conditions
and determine the area of each peak and calculate the
amount of each related substance: the amount of any related subtances is not more than 0.5% and the total
amount of related substances is not more than 1.0%.
Ai
Amount (%) of each related substance = 100 A
s
Ai : peak area of each related substance
As : the sum of all peak area obtained from the test
solution

Mobile phase : A mixture of water, tetrahydrofuran
and acetonitrile (8 : 1 : 1)
about 60 C
System suitability
System performance: Dissolve 10 mg of Finasteride RS in a mixture of water and acetonitrile (1 : 1) to
this solution under the above operating conditions, the
column efficiency is not less than 10000 theoretical
plates and the symmetry factor is not more than 1.3.
direct titration).
Assay Dissolve about 20 mg each of Finateride and Finasteride RS, accurately weighed, in a mixture of water
and acetonitrile (1 : 1) to make exactly 100 mL and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of
the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and determine the peak areas,
AT and AS, of the principal peak for the test solution and
Amount (mg) of f finasteride (C23H36N2O2)

AT
= amount (mg) of Finasteride RS A
S
Mobile phase : A mixture of water and tetrahydrofuran (4 : 1)
Flow rate: about 3 mL/minute
System suitability
with 10 L of the standard solution under the above operating conditions, the column efficiency is not less than
1800 theoretical plates and the symmetry factor is not
more than 1.3.
above operating conditions, the relative deviation of the
peak area is not more than 1.0%.

Flavin Adenine Dinucleotide

Sodium
NH2
N
H
H2C
H3C
H
CH2O
OH
OH
OH
P
O
ONa
OCH 2
NH
H3C
ONa
OH
OH
C27H31N9Na2O15P2: 829.51
Flavin Adenine Dinucleotide Sodium contains not less
than 93.0% and not more than 101.0% of flavin adenine
dinucleotide sodium (C27H31N9Na2O15P2), calculated on
Description Flavin Adenine Dinucleotide Sodium is an
orange-yellow to pale yellow-brown powder, is odorless
or has a slight, characteristic odor and has a slightly bitter taste.
Flavin Adenine Dinucleotide Sodium is freely soluble in
water and practically insoluble in methanol, in ethanol,
in ethylene glycol or in ether.
Flavin Adenine Dinucleotide Sodium is hygroscopic.
Flavin Adenine Dinucleotide Sodium is decomposed by
light.
Identification (1) A solution of Flavin Adenine Dinucleotide Sodium (1 in 100000) is pale yellow-green in
color and shows a strong yellow-green fluorescence.
Take 5 mL of the solution, and add 20 mg of hydrosulfite
sodium: the color and the fluorescence of the solution
disappear and gradually reappear when the solution is
shaken in air. Add dilute hydrochloric acid or sodium
hydroxide TS drop-wise: the fluorescence of the solution
disappears.
(2) Determine the infrared spectrum of Flavin Adenine Dinucleotide Sodium and Flavin Adenine Dinucleotide Sodium RS as directed in the potassium bromide
same wavenumbers.
(3) Take 0.1 g of Flavin Adenine Dinucleotide Sodium, add 10 mL of nitric acid, evaporate on a waterbath to dryness and ignite. To the residue, add 10 mL of
diluted nitric acid (1 in 50), boil for 5 minutes and after
cooling, neutralize with ammonia TS, then filter the solution, if necessary: the solution responds to the Qualitative
KP 9 411
Tests for sodium salt and the Qualitative Tests (1) and (3)
for phosphate.
D : Between -21.0 and 25.5 (0.3 g, calculated on the anhydrous basis, water, 20
mL, 100 mm).
pH Dissolve 1.0 g of Flavin Adenine Dinucleotide Sodium in 100 mL of water: the pH of this solution is between 5.5 and 6.5
0.20 g of Flavin Adenine Dinucleotide Sodium in 10 mL
of water: the solution is clear and orange-yellow in color.
20 mg of Flavin Adenine Dinucleotide Sodium, dissolve
in 10 mL of water and use this solution as the test solution. Separately, measure exactly 2 mL of standard phosphoric acid solution, add 10 mL of water and use this solution as the standard solution. To each of the test solution and the standard solution, add 2 mL of diluted perchloric acid (100 in 117), then add 1 mL of ammonium
molybdate TS and 2 ml of 2,4-diaminophenol hydrochloride TS, respectively, shake, add water to make exactly
25 mL and allow to stand at 20 1 o C for 30 minutes.
solution as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared in the same
manner with 2 mL of water, as the blank and determine
the standard solution at 730 nm, respectively: the amount
of free phosphoric acid is less than 0.25%.

=
AT
1
5 .16
AS W
W: Amount (mg) of Flavin Adenine Dinucleotide Sodium, calculated on the anhydrous basis.
(3) Heavy metalsProceed with 1.0 g of Flavin
Adenine Dinucleotide Sodium according to Method 2
(4) ArsenicPrepare the test solution With 2.0 g of
Flavin Adenine Dinucleotide Sodium according to Method 3 and perform the test (not more than 1 ppm).
(5) Related substancesDissolve 0.10 g of Flavin
Adenine Dinucleotide Sodium in 200 mL of the mobile
phase and use this solution as the test solution. Perform
conditions. Determine the peak area, A, of Flavin Adenine Dinucleotide and the area, S, of peaks other than the
peak of Flavin Adenine Dinucleotide by the automatic
integration method: S/(A+S) is not more than 0.10.

Column, column temperature, mobile phase, flow
rate, selection of column: Proceed as directed in operating conditions of Procedure (ii) under Assay (1).
System suitability
System performance: Proceed as directed in the
system suitability in Procedure (ii) under Assay (1).
mL, and use this solution as the solution for system suitability test. Confirm that the peak area of flavin adenine
dinucleotide obtained from 20 L of this solution is
equivalent to 8 to 12% of that of flavin adenine dinucleotide obtained from 20 L of the test solution.
times with 20 L of the solution for system suitability
test under the above operating conditions, the relative
standard deviation of the peak area of flavin adenine dinucleotide is not more than 1.0%.
Water Take 50 mL of a mixture of methanol for water
determination and ethylene glycol for water determination (1 : 1) into a dry titration flask and titrate with Karl
Fischer TS water determination until end point. Weigh
accurately about 0.1 g of Flavin Adenine Dinucleotide
Sodium, transfer quickly to the titration flask, add an
excess and constant volume of Karl Fischer TS water determination, dissolve by stirring for 10 minutes and perform the test: the water content is not more than 10.0%.
Assay Procedure (i) Total Flavin content: Conduct this
procedure without exposure to daylight, using lightresistant vessels. Weigh accurately about 0.1 g of Flavin
Adenine Dinucleotide Sodium and dissolve in water to
5 mL of zinc chloride TS and heat on a water-bath for 30
minutes. After cooling, add water to make exactly 100
weigh accurately about 50 mg of Riboflavin RS, previously dried at 105 C for 2 hours, dissolve in 200 mL
of diluted acetic acid (1 in 100) by warming, cool and
add water to make exactly 500 mL. Measure exactly 10
mL of this solution, add water to make exactly 100 mL
the standard solution at 450 nm, respectively, as directed
under the Ultraviolet-visible Spectrophotometry, using
water as the blank.
Total amount (mg) of Flavin = amount (mg) of

Riboflavin RS
AT 4
AS 5
(ii) Peak area ratio of Flavin Adenine Dinucleotide: Dissolve 0.1 g of Flavin Adenine Dinucleotide Sodium in
200 mL of water and use this solution as the test solution.
Perform the test with 5 L of this solution as directed

under the Liquid Chromatography according to the following conditions. Determine the peak area, A, of Flavin
Adenine Dinucleotide and the total area, S, of the peaks
other than Flavin Adenine Dinucleotide by the automatic
integration method.
Peak area ratio of Flavin Adenine Dinucleotide
= 1.08
1.08 A
10 .8 A + S
Detector: A visible spectrophotometer (wavelength:
450 nm).
about 35 o C .
Mobile phase: A mixture of a solution of monobasic
potassium phosphate (1 in 500) and methanol (4 : 1).
time of Flavin Adenine Dinucleotide is about 10 minutes.
System suitability
the test solution, add water to make exactly 20 mL, and
use this solution as the solution for system suitability test.
Pipet 2 mL of the solution, and add water to make exactly 20 mL. Confirm that the peak area of flavin adenine
dinucleotide obtained from 5 L of this solution is
equivalent to 8 to 12% of that of flavin adenine dinucleotide obtained from 5 L of the solution for system suitability test.
System performance: Dissolve about 20 mg each
of Flavin Adenine Dinucleotide Sodium and riboflavin
sodium phosphate in 100 mL of water. When the procedure is run with 5 L of this solution under the above
operating conditions and calculate the resolution, flavin
adenine dinucleotide and riboflavin phosphate in this order are eluted in this order with the resolution between
System repeatibility: When the test is repeated 6
times with 5 L of the solution for system suitability test
under the above operating conditions, the relative standard deviation of the peak area of flavin adenine dinucleotide is not more than 1.0%.
Time span of measurement: About 4.5 times as long as
the retention time of flavin adenine dinucleotide.
Amount (mg) of flavin adenine dinucleotide sodium
(C27H31N9Na2O15P2) = f T f R 2.2040
f T : Total amount (mg) of Flavin in Flavin Adenine
Dinucleotide Sodium obtained from the procedure (i),
f R : Peak area ratio of Flavin Adenine Dinucleotide in
Flavin Adenine Dinucleotide Sodium obtained from the
procedure (ii).

tight containers.
Flavoxate Hydrochloride
O
N
CH2CH2O
C
O
HCl
CH3
O
C24H25NO4HCl: 427.92
Flavoxate Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of flavoxate hydrochloried (C24H25NO4HCl).
Description Flavoxate Hydrochloride is a white crystal
Flavoxate Hydrochloride is sparingly soluble in glacial
acetic acid or chloroform, slightly soluble in water or
ethanol and practically insoluble in acetonitrile or ether.
the solutions of Flavoxate Hydrochloride and Flavoxate
Hydrochloride RS in 0.01 mol/L hydrochloric acid TS (1
(2) Determine the infrared spectrum of Flavoxate
Hydrochloride and Flavoxate Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Flavoxate Hydrochloride (1 in 100)
Purity (1) Heavy metalsProceed with 2.0 g of Flavoxate Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
Flavoxate Hydrochloride according to Method 4 and perform the test (not more than 1 ppm).
(3) Related substancesDissolve 80 mg of Flavoxate Hydrochloride in 10 mL of chloroform and use this
solution as the test solution. Pipet 1.0 mL of the test solution and add chloroform to make exactly 20 mL, then pipet 1.0 mL of this solution, add chloroform to make exactly 20 mL and use this solution as the standard solution.
solution as directed under the Thin-layer chromatography.
Spot 5 L each of the test solution and the standard solu-
KP 9 413
tion on a plate of silica gel with a fluorescent indicator
for Thin-layer chromatography. Develop the plate with a
mixture of n-butanol, water and glacial acetic acid (3 : 1 :
solution.

same wavelengths.
(2) Determine the infrared spectrum of Floctafenine
and Floctafenine RS, previously dried, as directed in the
Loss on Drying Not more than 1.0% (1 g, in vaccum,

Assay Weigh accurately about 0.6 g of Flavoxate Hydrochloride, previously dried, add 10 mL of glacial acetic
acid and 40 mL of acetonitrile to dissolve, add 50 mL of
acetic anhydride and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and

= 42.79 mg of C24H25NO4.HCl
Floctafenine
CF3
N
NH
O
OH
OCH2CCH2OH
H
and enantiomer
C20H17F3N2O4: 406.36
Floctafenine, when dried, contains not less than 98.5%

and not more than 101.0% of floctafenine
(C20H17F3N2O4).
Description Floctafenine is a white to pale yellowish
Floctafenine is freely soluble in glacial acetic acid,
slightly soluble in methanol or in ethanol, very slightly
soluble in ether and practically insoluble in water.
A solution of Floctafenine in 0.1 mol/L hydrochloric acid
TS (1 in 100) shows no specific rotation.
the solutions of Floctafenine and Floctafenine RS in 0.1
mol/L hydrochloric acid TS (1 in 100000) as directed
Purity (1) Heavy metalsProceed with 2.0 g of Floctafenine according to Method 2 and perform the test.
Floctafenine according to Method 4 and perform the test
(3) Related substancesDissolve 20 mg of Floctafenine in 50 mL of the mobile phase and use this solution
as the test solution. Pipet 1.0 mL of the test solution, add
to the following conditions. Determine each peak area
from both solutions by the automatic integration method:
the total area of the peaks other than the peak of Floctafenine from the test solution is not larger than the peak
area of Floctafenine from the standard solution.
about 25 C.
Mobile phase: Adjust the pH of a mixture of methanol, water and phosphoric acid (240 : 160 : 1) to 3.5 with
sodium hydroxide TS.
time of Floctafenine is about 6 minutes.
System suitability
System performance: Dissolve 10 mg of Floctafenine and 50 mg of ethyl parahydroxy-benzoate in 250
mL of the mobile phase. When the procedure is run with
20 L of this solution according to the above operating
conditions, Floctafenine and ethyl parahydroxybenzoate
so that the peak height of Floctafenine from 20 L of the
standard solution is between 5% and 15% of the full
scale.
Time span of measurement: About four times as long
as the retention time of Floctafenine after the solvent
peak.

hours).
Assay Weigh accurately about 0.6 g of Floctafenine,
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination above operating method and make any necessary correction.

= 40.64 mg of C20H17F3N2O4
Flopropione
COC2H5
HO
pione according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
Flopropione according to Method 3 and perform the test
(4) Related substancesDissolve 0.10 g of Flopropione in 10 mL of dehydrated ethanol and use this solution as the test solution. Pipet 1.0 mL of the test solution,
add dehydrated ethanol to make exactly 200 mL and use
plate of silica gel for Thin-layer chromatography. Develop the plate with a mixture of hexane, dehydrated ethanol and glacial acetic acid (40 : 20 : 1) to a distance of
about 10 cm and air-dry the plate. Spray evenly pnitrobenzene-diazonium TS for spraying on the plate and
dry in cold wind for about 5 minutes: the spots other than
direct titration).
OH

OH
C9Hl0O4: 182.17
Flopropione contains not less than 98.0% and not more
than 101.0% of flopropione (C9Hl0O4), calculated on the
anhydrous basis.
Description Flopropione is a white to pale yellowbrown, crystalline powder.
Flopropione is odorless and has a bitter taste.
Flopropione is very soluble in dimethylformamide, freely
soluble in methanol, in dehydrated ethanol or in ether
Identification (1) Take 1 mL of a solution of Flopropione in dehydrated ethanol (1 in 200), add 4 mL of water and 1 mL of ferric nitrate TS: a red-purple color is
observed.
(2) Determine the absorption spectra of the solutions of Flopropione and Flopropione RS in dehydrated
g of Flopropione in 10 mL of dehydrated ethanol: the solution is clear and has no more color than Matching Fluid
H.
(2) Heavy metalsProceed with 1.0 g of Flopro-
Assay Weigh accurately about 0.3 g of Flopropione,

dissolve in 30 mL of dimethyl-formamide and titrate
with 0.1 mol/L tetra-methylammonium hydroxide VS

hydroxide VS = 18.217 mg of C9Hl0O4
tight containers.
Flubendazole
O
H
N
CH3
O
N
H
N
O
C16H12FN3O3 : 313.28
Flubendazole contains not less than 99.0% and not more
than 101.0% of flubendazole (C16H12FN3O3), calculated
on the dried basis.
Description Flubendazole is white powder.
Flubendazole is practically insoluble in water, in dichlo-
KP 9 415
romethane or in ethanol.
Flubendazole shows polymorphism.
Identification Determine the infrared spectra of Flubendazole and Flubendazole RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity Related substancesDissolve 0.10 g of Flubendazole in dimethylformamide to make exactly 100
mL and use this solution as the test solution. Pipet exactly 1 mL of the test solutionn, add dimethylformamide to
make exactly 100 mL. Pipet exactly 5 mL of the this solutionn, add dimethylformamide to make exactly 25 mL
the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions: peak area of
any related substance with relative retention time between 1.2 and 1.3 is not more than that of the principal
peak from the standard solution (0.25%), and sum of
areas of peaks from the test solution except the principal
peak is not more than 6 times the area of the principal
peak from the standard solution (1.5%). Disregard peaks
from the test solution with areas of 0.2 times of the area
of the principal peak from the standard solution.
base-deactivated octadecylsilanized silica gel for liquid
Mobile phase : With the mobile phase A and the mobile B, control the composition stepwise or gradiently as
follows.
Mobile phase A: Dissolve 7.5 g of ammonium acetate in water to make 1000 mL.
Mobile phase B: Acetonitrile
Assay Weigh accurately about 0.25 g of Flubendazole,

dissolve in 3 mL of formic acid, add 50 mL of a mixture
of methyl ethyl ketone and glacial acetic acid (7 : 1) and

= 31.330 mg of C16H12FN3O3

Flucytosine
H
N
NH
F
NH2
C4H4FN3O: 129.09
Flucytosine, when dried, contains not less than 98.5%
and not more than 101.0% of flucytosine (C4H4FN3O)
and not less than 14.0% and not more than 15.5% of Fluorine (F: 19.00).
Description Flucytosine is a white, crystalline powder
and is odorless.
Flucytosine is sparingly soluble in water, slightly soluble
in methanol, in acetic anhydride, in glacial acetic acid or
Flucytosine dissolves in 0.1 mol/L hydrochloric acid TS.
The pH of a solution of Flucytosine (1 in 100) is between
5.5 and 7.5.
Flucytosine is slightly hygroscopic.

hours).
Identification (1) Take 5 mL of a solution of Flucytosine (1 in 500), add 0.2 mL of bromine TS: a yellowbrown color of bromine TS is immediately discharged.
Further add 2 mL of barium hydroxide TS: a purple precipitate is produced.
(2) Proceed with 0.1 g of Flucytosine as directed under the Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and
20 mL of water as the absorbing liquid. The solution responds to the Qualitative Tests (2) for fluoride.
of Flucytosine and Flucytosine RS in 0.l mol/L hydrochloric acid TS (1 in 125,000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
Time
(minutes)
Mobile phase
A (vol%)
Mobile phase
B (vol%)
0 ~ 15
15 ~ 30
30 ~ 32
32 ~ 37
37 ~ 38
38 ~ 42
90 75
75 45
45 10
10
10 90
90
10 25
25 55
55 90
90
90 10
10

g of Flucytosine in 100 mL of water: the solution is clear
and colorless.
(2) ChlorideDissolve 1.0 g of Flucytosine in 80
mL of water by heating on a water-bath. After cooling, to
40 mL of this solution, add 6 mL of dilute nitric acid and
0.014%).
(3) FluorideDissolve 0.10 g of Flucytosine in 10.0
mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20).
Transfer 5.0 mL of this solution to a volumetric flask,
add 10 mL of a mixture of alizarin complexone TS, acetic acid-potassium acetate buffer solution, pH 4.3 and
cerrous nitrate TS (1 : 1 : 1) and add water to make 20
mL. Allow the mixture to stand for 1 hour and use this
solution as the test solution. Separately, transfer 4.0 mL
of standard fluorine solution to a volumetric flask, add
5.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in
20), add 10 mL of a mixture of alizarin complexone TS,
acetic acid-potassium acetate buffer solution, pH 4.3 and
cerrous nitrate TS (1 : 1 : 1). Proceed in the same manner
as directed in the preparation of the test solution and use
this solution as the standard solution. Transfer 5.0 mL of
diluted 0.01 mol/L sodium hydroxide TS (1 in 20) to a
volumetric flask, proceed in the same manner as directed
in the preparation of the standard solution and use this
solution as the blank solution. Determine the absorbances, AT and AS , of the test solution and the standard solution at 600 nm, respectively, using the blank solution as the control as directed under Ultraviolet-visible
Spectrophotometry: AT is not larger than AS (not
more than 0.048%).
(4) Heavy metalsProceed with 1.0 g of Flucytosine
Flucytosine according to Method 2 and perform the test
(6) Related substancesDissolve 50 mg of Flucytosine in 5 mL of a diluted methanol (1 to 2) and use this
solution as the test solution. Pipet 1.0 mL of this solution,
add a diluted methanol (1 to 2) to make exactly 25 mL.
Pipet exactly 1 mL of this solution, add a diluted methanol (1 in 2) to make exactly 20 mL and use this solution
Thin-layer chromatography. Spot 20 L each of the test
with fluorescent indicator for Thin-layer chromatography.
Develop the chromatogram with a mixture of ethyl acetate, methanol and water (5 : 3 : 2) to a distance of about
12 cm, air-dry the plate and observe the spots under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot from the test solution are not
hours).
Assay (1) FlucytosineWeigh accurately about 0.2 g
of Flucytosine, previously dried, dissolve in 40 mL of
glacial acetic acid, add 100 mL of acetic anhydride and

= 12.909 mg of C4H4FN3O
(2) FluorineWeigh accurately about 10 mg of Flucytosine, previously dried and proceed as directed in the
determination of fluorine under the Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L
sodium hydroxide VS and 20 mL of water as the absorbing liquid.
tight containers.
Fludiazepam
CH3
O
N
Cl
N
F
C16H12ClFN2O: 302.73
Fludiazepam, when dried, contains not less than 99.0%
and not more than 101.0% of fludiazepam (C16H12ClF
N2O).
Description Fludiazepam is a white to pale yellow
Fludiazepam is very soluble in chloroform, freely soluble
in methanol, in ethanol, in glacial acetic acid or in ether
Identification (1) Prepare the test solution with 10 mg
of Fludiazepam as directed under the Oxygen Flask
Combustion Method, using a mixture of 0.5 mL of 0.01
mol/L sodium hydroxide TS and 20 mL of water as the
absorbing liquid: the test solution responds to the Qualitative Tests (2) for fluoride.
of Fludiazepam and Fludiazepam RS in methanol (1 in
200000) as directed under the Ultraviolet-visible Spec-
KP 9 417
trophotometry: both spectra exhibit similar intensities of
absorption at the same wavelengths. And determine spectra of the solutions of Flueliazepam and Fludiazepam RS
in methonol (1 in 20000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths
(3) Determine the infrared spectrum of Fludiazepam
and Fludiazepam RS, previously dried, as directed in the
(4) Perform the test with Fludiazepam as directed
under the Flame Coloration Test (2): a green color is observed.
Purity (1) ChlorideDissolve 1.0 g of Fludiazepam in
50 mL of ether, add 50 mL of water and shake. Separate
the water layer, wash with two 20 mL volumes of ether
and filter the water layer. To 20 mL of the filtrate, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.036%).
(2) Heavy metalsProceed with 2.0 g of Fludiazepam according to Method 2 and perform the test. Prepare
(3) Related substancesDissolve 0.10 g of Fludiazepam in 20 mL of chloroform and use this solution as
the test solution. Pipet 1.0 mL of the test solution and
add chloroform to make exactly 50 mL. Pipet 2.0 mL of
this solution, add chloroform to make exactly 20 mL and
plate of silica gel with fluorescent indicator for Thinlayer chromatography. Develop the plate with a mixture
of chloroform and ethyl acetate (10 : 7) to a distance of
60 o C , 3 hours).
Assay Weigh accurately about 0.5 g of Fludiazepam,

= 30.273 mg of C16H12ClFN2O
Fludrocortisone Acetate
O
OH
H3C
H
CH3
HO
O
CH3
O
H
C23H31FO6: 422.49
Fludrocortisone Acetate, when dried, contains not less
than 97.0% and not more than103.0% of fludrocortisone
acetate (C23H31FO6).
Description Fludrocortisone Acetate is a white to pale
yellow crystal or crystalline powder, is odorless or has
slight odor.
Fludrocortisone Acetate is hygroscopic.
Fludrocortisone Acetate is hardly soluble in ether,
slightly soluble in ethanol or in chloroform and practically insoluble in water.
Identification Determine the infrared spectra of Fludrocortisone Acetate and Fludrocortisone Acetate RS, as directed in the paste method under the Infrared Spectrophotometry: both spectra similar intensities of absorption
at the same wavenumbers.
+ 138 (dried, 50 mg, acetone, 10 mL, 100 mm).
0.1 g of Fludrocortisone Acetate and dissolve in 5 mL of
chloroform and 1 mL of acetone and dilute with chloroform to make 10 mL. Use this solution as the test solution. Dilute 1 mL of this solution with chloroform to
make 100 mL. Use this solution as the standard solution.
Proceed with the test solution as the standard solution
and perform the test directed under Thin Layer Chromatography. Spot 10 L each of the test solution and the
standard solution on a silica gel plate. Develop the plates
with developing solution of a mixture of chloroform, methanol and water (85 : 14 : 1) to the distance of about 15
cm and air-drying. When infrared line (wavelength : 254
nm) was lighted on these plates, black spots of the test
solution, except main black spot, are smaller and less
darker than that of the standard solution (not more than
1.0%).
Loss on Drying Not more than 3.0% (1 g, 100 C, in

vacuum, magnesium perchlorate, 2 hours).
Assay Weigh accurately about 25 mg of Fludrocortisone Acetate and Fludrocortisone Acetate for Assay, previously dried at 100 C for 2 hours in vacuum and dissolve in chloroform to make 250 mL. Pipet 10.0 mL of
this solution and dilute with chloroform to make 50 mL
and use these solutions as the test solution and the standard solution, respectively. Pipet 10.0 mL each of the test
solution and the standard solution into a volumetric flask
and add 1 mL of methanol solution of bluetetrazolium
(dissolve 50 mg of bluetetrazolium in 10 mL of methanol) and mix. Add 1.0 mL of a mixture of tetramethylammonium hydroxide solution and methanol (1 : 4) and
stand for 10 minutes. Add a mixture of hydrochloric acid
and methanol (1 in 100) to make exact 25 mL. Perform
the test with 10 mL each of the test solution and the standard solution as directed under the Ultraviolet-visible
Spectrophotometry. Determine absorbances, AT and
AS , of Fludrocortisone Acetate of the test solution and
standard solution, respectively, at a maximum wavelength near 525 nm.
Amount (mg) of fludrocortisone acetate (C23H31FO6)

= amount of Fludrocortisone Acetate RS
AT
AS
C: Concentration of the standard solution (L/mL).


well-closed Containers.
Flumequine
H
CH3
COOH
O
Zirconyl nitrate solutionDissolve 0.1 g of zirconyl

nitrate in a mixture of 60 mL of hydrochloric acid and 40
mL of water.
(2) Determine the infrared absorption spectra of Flumequine and Flumequine RS as directed in the potassiumn bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Dissolve 5 mg of Flumequine in dichloromethane
to make 10 mL and use this solution as the test solution.
Separately, dissolve 5 mg of Flumequine RS in dichloromethane to make 10 mL and use this solution as the
and the standard solution as directed under the Thinlayer Chromatography. Spot 5 L each of the test solution and the standard solution on a plate of silica gel with
fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethanol, water and 9
mol/L ammonia solution TS (90 : 10 : 10) to a distance
of about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal
spots obtained from the test solution and the standard solution has the same Rf value.
9 mol/L ammonia solutionTo 67 g of 13.5 mol/L
ammonia solution, add water to make 100 mL.
Identification (1) Mix 5 mg of Flumequine with 45

mg of magnesium oxide and ignite for about 5 minutes
until an almost white residue is obtained. After cooling,
add 1 mL of water and 2 drops of phenolphthalein TS,
add about 2 mL of dilute hydrochloric acid to render the
solution colorless. Filter and use the filtrate as the test solution. Add to the test solution a freshly prepared mixture
of 0.1 mL of alizarin S TS and 0.1 mL of the zirconyl nitrate solution, mix, allow to stand 5 minutes and compare
the color of the solution with that of the blank solution
prepared in the same manner: the color of the test solution changes from red to yellow, while the color of the
blank solution remains red.
and enantiomer
C14H12FNO3 : 261.25
Flumequine containes not less than 99.0% and not more

than 101.0% of flumequine (C14H12FNO3), calculated on
the dried basis.
Description Flumequine is a white, fine crystalline
powder.
Flumequine is sparingly soluble in dichloromethane,
very slightly soluble in methanol, and practically insoluble in water.
Flumequine dissolves in dilute sodium hydroxide TS.

+0.10 (5.0 g, sodium hydroxide TS, 50 mL, 100mm).
g of Flumequine in 0.5 mol/L sodium hydroxide TS to
make 50 mL: the solution is clear.
(2) Heavy metalsProceed with 2.0 g of Flumequine
control solution with 2.0 mL of Standard Lead Solution
(3) Related substancesDissolve 35.0 g of Flumequine in dimethylformamide to make exactly 100 mL
and use this solution as the test solution. Separately, dissolve 5.0 mg each of flumequine RS and flumequine related substance I RS [(RS)-9-fluoro-5-methyl-1-oxo-6,7dihydro-1H,5H-benzo[i.j]quinolizine-2-carboxylate
KP 9 419
(flumequine ethyl ester)] in dimethylformamide to make
exactly 100 mL and use this solution as the standard solution (1). To 1.0 mL of the test solution, add dimethylformamide to make exactly 200 mL and use this solution
as the standard solution (2). Perform the test with 10 L
each of the blank solution (dimethylformamide), the test
solution and the standard solutions (1) and (2) as directed
under the Liquid Chromatography according to the following conditions: area of any peak from the test solution except the principal peak is not more than that of
the principal peak from the standard solution (2) (0.5%),
and sum of areas of peaks from the test solution except
the principal peak is not more than 2 times the area of the
principal peak from the standard solution (2) (1.0%).
Disregard peaks from dimetylformamide and the test solution with areas of 0.1 times of the area of the principal
peak from the standard solution (2).
Mobile phase : A mixture of the potassium dihydrogen phosphate buffer and methanol (51 : 49)
System suitability
System performance: When the procedure is
formed accoding to the above operating conditions, retention times of flumequine related substance I RS and
flumequine are about 11 minutes and 13 minutes, respectively and the resolution between these peaks is not less
than 2.0.
Potassium dihydrogen phosphate bufferDissolve
1.36 g of potassium dihydrogen phosphate in water to
make 1000 mL.
hours).
Assay Weigh accurately about 0.5 g of Flumequine,
dissolve in 50 mL of dimethylformamide and titrate with
0.1 mol/L tetrabutylammonium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L tetrabutylammonium hydroxide

VS = 26.126 mg of C14H12FNO3
Flunitrazepam
CH3
O
N
O2N
N
F
Cl6H12FN3O3: 313.28
Flunitrazepam, when dried, contains not less than 99.0%
and not more than 101.0% of flunitrazepam
(Cl6H12FN3O3).
Description Flunitrazepam is a white to pale yellow
crystalline powder.
Flunitrazepam is freely soluble in glacial acetic acid, soluble in acetic anhydride or in acetone, slightly soluble in
dehydrated ethanol or in ether and practically insoluble
in water.
the solutions of Flunitrazepam and Flunitrazepam RS in
dehydrated ethanol (1 in 100000) as directed under the
(2) Determine the infrared spectrum of Flunitrazepam and Flunitrazepam RS, previously dried, as directed
Purity (1) ChlorideTake 1.0 g of Flunitrazepam, add
50 mL of water, allow to stand for 1 hour with occasional
stirring and filter. To 20 mL of the filtrate, add 6 mL of
dilute nitric acid and water to make 50 mL and perform
the test with this solution. Prepare the control solution
more than 0.022%).
(2) Heavy metalsProceed with 2.0 g of Flunitrazepam according to Method 4 using a platinum crucible
(3) Related substancesDissolve 50 mg of Flunitrazepam in 10 mL of acetone and use this solution as the
test solution. Pipet 2.0 mL of the test solution and add
acetone to make exactly 20 mL. Pipet 1.0 mL of this solution, add acetone to make exactly 25 mL and use this
the test solution and the standard solution as directed under the Thin-layer chromatography. Spot 10 L each of

silica gel with fluorescent indicator for Thin-layer chromatography. Develop the plate with a mixture of 1,2dichloroethane, ether and strong ammonia water (200 :
nm): numbers of the spots other than the principal spot
from the test solution are not more than 2 and they are
hours).
Assay Weigh accurately about 0.5 g of Flunitrazepam,
add 50 mL of acetic anhydride and titrate with 0.1 mol/L

= 31.328 mg of Cl6H12FN3O3

tight containers.
Fluocinolone Acetonide
O
H3C
CH2OH
HO
H
H3C
CH3
CH3
H
F
O
H
C24H30F2O6: 452.49
Fluocinolone Acetonide, when dried, contains not less
than 97.0% and not more than 102.0% of fluocinolone
acetonide (C24H30F2O6).
Description Fluocinolone Acetonide is a white crystal
or crystalline powder. Fluocinolone Acetonide is odorless.
Fluocinolone Acetonide is freely soluble in glacial acetic
acid or acetone, soluble in ethanol or dehydrated ethanol,
sparingly soluble in methanol or chloroform, slightly soluble in acetonitrile, very slightly soluble in ether, and
Melting pointBetween 266 C and 274 C (with
decomposition).
Identification (1) Take 2 mg of Fluocinolone Acetonide, add 2 mL of sulfuric acid: a yellow color is observed.
(2) Dissolve 10 mg of Fluocinolone Acetonide in 1

mL of methanol, add 1 mL of Fehling TS and heat: a red
precipitate is produced.
(3) Proceed with 10 mg of Fluocinolone Acetonide as
using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as an absorbing liquid. The
test solution responds to the Qualitative Tests for fluoride.
(4) Determine the infrared spectra of Fluocinolone
Acetonide and Fluocinolone Acetonide RS, previously
under the Infrared Spectrophotometry, respectively: both
spectra exhibit the similar intensity of absorption at the
same wavenumbers. If any difference appears in the absorption spectra, dissolve the test and the RS in acetone,
respectively, evaporate acetone and perform the test with
the residue in the same manner.
D : Between +98 and
Purity Related substancesDissolve about 15 mg of
Fluocinolone Acetonide in 25 mL of mobile phase and
of this solution, add mobile phase to make exactly 100
standard solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area of the test solution and the standard
solution by the automatic integration method: the total
area of all peaks other than the peak of Fluocinolone
Acetonide from the test solution is not larger than the
peak area of Fluocinolone Acetonide from the standard
solution.
about 30 C.
Mobile phase: A mixture of chloroform saturated
with water, methanol and glacial acetic acid (200 : 3 : 2).
Flow rate: Adjust the flow rate so that the retention time
of Fluocinolone Acetonide is about 12 minutes.
System suitability
System performance: Dissolve each 15 mg of Fluocinolone Acetonide and Triamcinolone Acetonide in 25
mL of the mobile phase. Take 5 mL of this solution, add
mobile phase to make 20 mL. When the procedure is run
with 20 L of this solution, as directed under the above
operating conditions, Triamcinolone Acetonide and Fluocinolone Acetonide are eluted in this order with a resolution between their peaks being not less than 1.9.
KP 9 421
under the above operating conditions, the relative deviation of the peak area of Fluocinolone Acetonide is not
more than 1.0%.
Test for required detection: Take exactly 5 mL of
the standard solution add the mobile phase to make exactly 100 mL. Confirm that the peak area of Fluocinolone acetonide obtained from 20 L of this solution is
equivalent to 4 to 6% of that of Fluocinolone acetonide
obtained from 20 L of the standard solution.
the retention time of Fluocinolone Acetonide.
ditions, isopropyl p-hydroxybenzoate and propyl phydroxybenzoate are eluted in this order with a resolution between their peaks being not less than 1.9.
more than 1.0%.

105 C, 3 hours).
Fluocinolone Acetonide Cream
Fluocinolone Acetonide Cream contains not less than

of fluocinolone acetonide (C24H30F2O6: 452.49).
Assay Weigh accurately about 20 mg each of Fluocinolone Acetonide and Fluocinolone Acetonide RS, previously dried, dissolve in 40 mL of methanol, add exactly 10 mL of the internal standard solution, add water to
with 20 L each of the test solution and the standard solution as directed under Liquid Chromatography according to the following conditions and calculate the ratios,
QT and QS , of the peak area of Fluocinolone Acetonide to that of the internal standard for the test solution
Amount (mg) of fluocinolone acetonide (C24H30F2O6)

= amount (mg) of Fluocinolone Acetonide RS
QT
QS
Internal standard solutionA solution of ethyl parahydroxybenzoate in methanol (1 in 2500).

about 40 C.
3).
time of Fluocinolone Acetonide is about 20 minutes.
System suitability
System performance: Dissolve 5 mg each of isopropyl parahydroxybenzoate and propyl parahydroxybenzoate in 50 mL of acetonitrile and add water to
make 100 mL. When the precedure is run with 20 L of
this solution, as directed under the above operating con-

tight containers.

Creams, with Fluocinolone Acetonide.
Identification Weigh accurately a portion of Fluocinolone Acetonide Cream, equivalent to about 0.5 mg of
fluocinolone acetonide (C24H30F2O6) according to the labeled amount, transfer to a centrifugal tube, suspend with
5 mL of water, add 10 mL of chloroform, shake and centrifuge. Discard the water layer, add 10 mL of water,
shake and centrifuge. Dehydrate 2 mL of chloroform extracts with about 0.2 g of anhydrous sodium sulfate and
5 mg of Fluocinolone Acetonide RS in 100 mL of chloroform and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer chromatography.
for Thin-layer chromatography. Develop the chromatogram with a mixture of chloroform and diethylamine (2 :
the principal spot from the test solution shows the same
Rf value and color as the principal spot from the standard solution.
Microbiology Limit When the test is performed, Staphylococcus aureus and Pseudomonas aeruginosa are not
detected.
Assay Weigh accurately a portion of Fluocinolone Acetonide Cream, equivalent to about 0.75 mg of fluocinolone acetonide (C24H30F2O6), add about 10 mL of acetonitrile and warm in the water-bath until dissolved. Transfer to a 25 mL volumetric flask with aid of three 2 mL
volumes of acetonitrile. To this solution, add 3.0 mL of
the internal standard solution and 5.0 mL of water, shake,
add acetonitrile to make 25 mL, cool in the ice-bath, centrifuge and use the supernatant as the test solution. Sepa-

rately, weigh accurately a portion of Fluocinolone Acetonide RS, previously dried at 105 C for 3 hours, dissolve in acetonitrile to obtain a solution having a known
concentration of about 300 g per mL. Pipet exactly 5
mL of this solution, add 6.0 mL of the internal standard
solution and 15.0 mL of water, add acetonitrile to make
exactly 50 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution
and the standard solution as directed under Liquid
and calculate the ratios, QT and QS , of the peak area
of Fluocinolone Acetonide to that of the internal standard
= amount (mg) of Fluocinolone Acetonide RS
QT
QS
Internal standard solutionA solution of norethindrone in acetonitrile (2 in 10000).

Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, having octadecylsilanized silica gel for liquid chromatography (5 to 10
5).
System suitability
above operating conditions, the resolution between peaks
of the internal standard and fluocinolone acetonide being
not less than 2.0.
times with 10 L of the standard solution, as diredcted
more than 1.5%.
Fluocinolone Acetonide
Ointment
Fluocinolone Acetonide Ointment contains not less than
of fluocinolone acetonide (C24H30F2O6: 452.49).
Ointments, with Fluocinolone Acetonide.
Identification Evaporate 10 mL of the test solution in

the Assay to dryness, dissolve the residue in 1 mL of
chloroform and use this solution as the test solution.
Separately, dissolve 5 mg of Fluocinolone Acetonide RS
in 100 mL of chloroform and use this solution as the
the chromatogram with a mixture of chloroform and diethylamine (2 : 1) to a distance of about 12 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal spot from the test solution
shows the same Rf value and color as the principal spot
Microbiology Limit When the test is performed, Staphylococcus aureus and Pseudomonas aeruginosa are not
detected.
Assay Weigh accurately a portion of Fluocinolone Acetonide Ointment, equivalent to about 0.7 mg of fluocinolone acetonide (C24H30F2O6), transfer to a 50 mL centrifugal tube, suspend with 35.0 mL of diluted internal
standard solution using sonicator, centrifuge and use the
supernatant as the test solution. Separately, weigh accurately a portion of Fluocinolone Acetonide RS, previously dried at 105 o C for 3 hours, dissolve in acetonitrile to
obtain a solution having a known concentration of about
200 g/mL. Pipet exactly 10 mL of this solution, add 2.0
mL of the internal standard solution, add methanol to
peak area of Fluocinolone Acetonide to that of the internal standard for the test solution and the standard solution, respectively.

= amount (mg) of Fluocinolone Acetonide RS QT
QS
Internal standard solutionA solution of norethindrone in methanol (1.7 in 200000).

Column: A stainless steel column, about 4 mm in inside diameter and about 50 cm in length, having octadecylsilanized silica gel for liquid chromatography (5 m
to10 m in particle diameter).
KP 9 423
1).
System suitability
System performance: When the test procedure is
run with 10 L of the standard solution as directed under
the above operating conditions, the resolution between
times and the relative standard deviation of the ratios of
the peak area is not more than 1.5%.
Detection of sensitivity: Adjust the peaks of each component to be less than 50% and not more than 90%
of full scale.
Diluted internal standard solutionDilute 5.0 mL of
the internal standard solution with methanol to make 250
mL.
Fluocinonide
O
H
H3C
CH2O
HO
H3C
CH3
CH3
CH3

D : Between +81 and
+89 (after drying, 0.2 g, chloroform, 20 mL, 100 mm).
Purity Related substancesDissolve 10 mg of Fluocinonide in 2 mL of chloroform and use this solution as
add chloroform to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
the Thin-layer chromatography. Spot 10 L each of the
gel for Thin-layer chromatography. Develop the plate
with a mixture of chloroform and methanol (97 : 3) to a
evenly alkaline blue tetrazolium TS on the plate: any
spot other than the principal spot from the test solution is
hours).
H
F
(4) Determine the infrared spectra of Fluocinonide

and Fluocinonide RS, previously dried, as directed in the
difference appears in the absorption spectra, dissolve the
test and the RS in ethyl acetate, respectively, evaporate
the ethyl acetate and perform the test with the residue in
the same manner.
O
H
C26H32F2O7: 494.53
Fluocinonide, when dried, contains not less than 97.0%
and not more than 103.0% of fluocinonide (C26H32F2O7).
Description Fluocinonide is a white crystal or crystalline powder.
Fluocinonide is sparingly soluble in chloroform, slightly
soluble in acetonitrile, methanol, ethanol or ethyl acetate,
very slightly soluble in ether, and practically insoluble in
water.
Identification (1) Take 10 mg of Fluocinonide, add 4
mL of water and 1 mL of Fehling's TS and heat: a red
(2) Prepare the test solution with 10 mg of Fluocinonide as directed under the Oxygen Flask Combustion
the test solution responds to the Qualitative Tests for fluoride.
Fluocinonide and Fluocinonide RS, respectively, in methanol (1 in 10000) as directed under Ultraviolet-visible

Assay Weigh accurately about 20 mg of Fluocinonide
and fluocinonide RS, previously dried, dissolve each in
50 mL of acetonitrile, to each add exactly 8 mL of the internal standard solution and water to make 100 mL and
solution, respectively. Perform the test with 20 L each
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS ,
of the peak area of Fluocinonide to that of the internal
respectively.
Amount (mg) of fluocinonide (C26H32F2O7)

= amount (mg) of Fluocinonide RS
QT
QS
Internal standard solutionA solution of propyl

benzoate in acetonitrile (1 in 100).

about 40 C.
1).
time of Fluocinonide is about 8 minutes.
System suitability
above operating conditions, Fluocinonide and the internal standard are eluted in this order with a resolution between their peaks being not less than 6.
under the above operating conditions and the relative
deviation of the peak area of Fluocinonide is not more
than 1.0%.
Fluorescein Sodium
NaO
CO2Na
C20H10Na2O5: 376.27
Fluorescein Sodium contains not less than 98.5% and not
more than 101.0% of fluorescein sodium (C20H10Na2O5),
Description Fluorescein Sodium is an orange powder,
is odorless and tasteless.
Fluorescein Sodium is freely soluble in water, in methanol or in ethanol and practically insoluble in ether.
Fluorescein Sodium is hygroscopic.
Identification (1) Take a solution of Fluorescein Sodium (1 in 100) having a strong green fluorescence, add
a large volume of water: the fluorescence remains. Acidify the solution with hydrochloric acid: the fluorescence
disappears. Then render the solution alkaline with sodium hydroxide TS: the fluorescence reappears.
(2) Place 1 drop of a solution of Fluorescein Sodium
(1 in 2000) on a piece of filter paper: a yellow spot develops. Expose the spot, while moist, to the vapor of
bromine for 1 minute and then to ammonia vapor: the
yellow color of the spot changes to red.
(3) Char 0.5 g of Fluorescein Sodium by ignition,

cool, mix the residue with 20 mL of water and filter: the
filtrate responds to the Qualitative Tests for sodium salt.
g of Fluorescein Sodium in 10 mL of water: the solution
is clear and shows a red color.
(2) ChlorideDissolve 0.15 g of Fluorescein Sodium in 20 mL of water, add 6 mL of dilute nitric acid
and water to make 30 mL and filter. Take 20 mL of the
filtrate, add 2 mL of dilute nitric acid and water to make
(3) SulfateDissolve 0.20 g of Fluorescein Sodium
in 30 mL of water, add 2.5 mL of dilute hydrochloric acid and water to make 40 mL and filter. To 20 mL of the
filtrate, add water to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control solution with 1.0 mL of 5 mmol/L sulfuric acid VS (not more
than 0.480%).
(4) ZincDissolve 0.1 g of Fluorescein Sodium in
10 mL of water, add 2 mL of hydrochloric acid and filter.
To the filtrate, add 0.1 mL of potassium ferrocyanide TS:
no turbidity is produced immediately.
(5) Related substancesDissolve 0.20 g of Fluorescein Sodium in 10 mL of methanol and use this solution as the test solution. Perform the test with this solution as directed under the Thin-layer chromatography.
Spot 5 L of the test solution on a plate of silica gel for
Thin-layer chromatography. Develop the plate with a
mixture of chloroform, methanol and strong ammonia
water (30 : 15 : 1) to a distance of about 10 cm and airdry the plate: any colored spot other than the principal
spot does not appear.
constant weight).
Assay Transfer 0.5 g of Fluorescein Sodium, accurately weighed, to a separator. Dissolve in 20 mL of water,
add 5 mL of dilute hydrochloric acid and extract the solution with four 20 mL volumes of a mixture of isobutanol and chloroform (1 : 1). Wash each extract with 10 mL
of water. Evaporate the combined extracts on a waterbath with the aid of a current of air. Dissolve the residue
in 10 mL of dehydrated ethanol, evaporate the solution
on a water-bath to dryness, dry the residue at 105 o C for
1 hour and weigh as fluorescein (C20H12O5: 332.31).
Amount (mg) of C20H10Na2O5

= amount (mg) of fluorescein (C20H12O5) 1.1323
KP 9 425
Fluorometholone
O
CH3
H
HO
CH3
CH3
OH

P2O5, 60 C, 3 hours).
O
H
fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, acetone and methanol (45 : 5 : 1) to a distance of about 12
cm, and air-dry the plate. Examine under ultraviolet light
CH3
C22H29FO4 : 376.46
Fluorometholone, when dried, contains not less than
97.0% and not more than 103.0% of fluorometholone
(C22H29FO4).
Description Fluorometholone is as a white to light yellowish white, crystalline powder and is odorless.
Fluorometholone is freely soluble in pyridine, slightly
soluble in methanol, in ethanol or in tetrahydrofuran, and
practically insoluble in water or in ether.
Identification (1) Proceed with 7 mg of Fluorometholone as directed under Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L sodium
the liquid responds to the Qualitative Tests (2) for fluoride.
Fluorometholone and Fluorometholone RS in methanol
(1 in 100,000) as directed under the Ultraviolet-visible
(3) Determine the infrared absorption spectra of Fluorometholone and Fluorometholone RS, previously dried,
as directed in the potassiumn bromide disk method under
D : Between +52 and
+60 (after drying, 0.1 g, pyridine, l0 mL, 100mm).
Purity (1) Heavy metalsProceed with l.0 g of Fluorornetholone according to Method 3, and performn the
test. Prepare the control solution with 2.0 mL of Standard
(2) Related substancesDissolve 20 mg of Fluorometholone in 10 mL of tetrahydrofuran, and use this solution as the test solution. Pipet exactly 1 mL of the test
solution, add tetrahydrofuran to make exactly 100 mL,
Assay Weigh accurately about 0.1 g each of Fluorometholone and Fluorometholone RS, previously dried, and
dissolve each in methanol to make exactly 100 mL. Pipet
exactly 5 mL each of these solutions, and add diluted
methanol (7 in 10) to make exactly 50 mL. Pipet exactly
10 mL each of these solutions, add exactly 10 mL of the
internal standard solution and diluted methanol (7 in 10)
to make 100 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the
according to the following conditions and determine the
ratios, QT and QS, of the peak area of fluorometholone to
that of the internal standard.
Amount (mg) of fluorometholone (C22H29FO4) = amount

QT
(mg) of Fluorometholone RS Q
S
Detector: An ultraviolet absorption photometer (wavelength: 254 nmn).
Column: A stainless steel column about 4 nim in inside diameter and 25 to 30 cm in length, packed with
ociadecylsilanized silica gel for liquid chromatography
about 35 C.
Mobile phase: Diluted methanol (7 in 10).
time of fluorometholone is about 8 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, fluorometholone and the internal
standard in this order with the resolution between these
Fluorouracil
H
N
NH
F
O
C4H3FN2O2: 130.08
Fluorouracil, when dried, contains not less than 98.5%
and not more than 101.0% of fluorouracil (C4H3FN2O2)
and not less than 13.1% and not more than 16.1% of fluorine (F: 19.00).
Description Fluorouracil is a white crystal or crystalline powder and is odorless.
Fluorouracil is freely soluble in dimethylformamide, sparingly soluble in water, slightly soluble in ethanol and
Identification (1) Take 5 mL of a solution of Fluorouracil (1 in 500), add 0.2 mL of bromine TS: the color of
bromine TS is discharged. Further add 2 mL of barium
hydroxide TS: a purple precipitate is produced.
(2) Proceed with 10 mg of Fluorouracil as directed
under the Oxygen Flask Combustion Method, using a
mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS
and 20 mL of water as the absorbing liquid. The test solution responds to the Qualitative Tests for fluoride.
of Fluorouracil and Fluorouracil RS in 0.1 mol/L hydrochloric acid VS (1 in 100000) as directed under the
Purity (1) Clarity and color of solutionAdd 20 mL
of water to 0.20 g of Fluorouracil and dissolve by warming: the solution is clear and colorless.
(2) FluorideDissolve 0.10 g of Fluorouracil in
10.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1
in 20). Transfer 5.0 mL of this solution to a volumetric
flask, add 10 mL of a mixture of alizarin complexone TS,
acetic acid-potassium acetate buffer solution, pH 4.3 and
cerous nitrate TS (1 : 1 : 1) and add water to make 20 mL.
Allow to stand for 1 hour and use this solution as the test
solution. Separately, transfer 1.0 mL of standard fluorine
solution to a volumetric flask, add 5.0 mL of diluted 0.01
mol/L sodium hydroxide TS (1 in 20) and add 10 mL of a
mixture of alizarin complexone TS, acetic acidpotassium acetate buffer solution, pH 4.3 and cerous nitrate TS (1 : 1 : 1). Proceed in the same manner as directed for the preparation of the test solution and use this
solution as the standard solution. Perform the test as directed under the Ultraviolet-visible Spectrophotometry,
using a solution, prepared with 5.0 mL of diluted 0.01
mol/L sodium hydroxide TS (1 in 20) in the same manner,

as the blank: the absorbance of the test solution at 600
nm is not larger than that of the standard solution (not
more than 0.012%).
(3) Heavy metalsProceed with 1.0 g of Fluorouracil according to Method 2 and perform the test. Prepare
(4) ArsenicTo 1.0 g of Fluorouracil in a crucible,
add 10 mL of a solution of magnesium nitrate in ethanol
(1 in 10), ignite the ethanol to burn and incinerate by
strong heating at 750 C to 850 C. If a carbonized substance remains in this method, moisten with a small
amount of nitric acid and incinerate by strong heating.
Cool, add 10 mL of dilute hydrochloric acid to the residue, dissolve by warming on a water-bath, use this solution as the test solution and perform the test (not more
than 2 ppm).
(5) Related substancesDissolve 0.10 g of Fluorouracil in 10 mL of water and use this solution as the test
solution. Measure exactly 1 mL of this solution, add water to make exactly 200 mL and use this solution as the
the plate with a mixture of ethyl acetate, acetone and water (7 : 4 : 1) to a distance of about 12 cm, air-dry the
plate and examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
80 C, 4 hours).
Assay (1) FluorouracilWeigh accurately about 0.2 g
of Fluorouracil, previously dried, dissolve in 20 mL of
dimethylformamide and titrate with 0.1 mol/L tetramethylammonium hydroxide VS until the color of the solution changes from yellow through blue-green to blue (indicator: 3 drops of thymol blue-dimethylformamide TS).
correction.

hydroxide VS = 13.008 mg of C4H3FN2O2
(2) FluorineWeigh accurately about 4 mg of Fluorouracil, previously dried and proceed as directed in the
determination of fluorine under the Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L
sodium hydroxide TS and 20 mL of water as the absorbing liquid.
KP 9 427
Fluorouracil Cream
Fluorouracil Injection
Fluorouracil Cream contains not less than 90.0% and not

more than 110.0% of the labeled amount of fluorouracil
(C4H3FN2O2: 130.08).
Fluorouracil Injection is an aqueous solution for injection.

Fluorouracil Injection contains not less than 90.0% and
not more than 110.0% of the labeled amount of fluorouracil (C4H3FN2O2: 130.08).

Creams, with Fluorouracil. Sodium hydroxide may be
added to adjust the pH.
Identification Transfer, accurately weighed, a portion
of fluorouracil Cream, equivalent to about 5 mg of Fluorouracil, to a stoppered conical flask, add 50 mL of ethanol, shake until dissolved and use this solution as the test
solution. Separately, weigh 5 mg of fluorouracil RS, dissolve in 50 mL of ethanol and use this solution as the
chromatography. Spot 100 L each of the test solution
and the standard solution (5 times with 20 L) on a line
about 3 cm from the bottom edge of a thin-layer chromatographic plate coated with a 25-m layer of silica gel, develop the chromatogram with a mixture of ethyl acetate,
methanol and strong ammonia water (75 : 25 : 1) to a
distance of about 15 cm and remove and air-dry the plate.
Observe the spots under ultraviolet light (main wavelength: 254 nm): the spots from the test solution and the
standard solution show the same Rf value.
Assay Weigh accurately a portion of Fluorouracil
Cream, equivalent to about 10 mg of fluorouracil
(C4H3FN2O2), add 20 mL of methanol, shake and add
water to make exactly 100 mL. Pipet 1.0 mL of this solution, add water to make 100 mL, filter and use this filtrate as the test solution. Separately, weigh accurately
about 10 mg of Fluorouracil RS, previously dried, dissolve in water to make 100 mL, pipet 1.0 mL of this solution, add water to make 10 mL and use this solution as
the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions: determine the peak areas, AT and AS ,
of Fluorouracil, for the test solution and the standard solution, respectively.
Amount (mg) of fluorouracil (C4H3FN2O2)

= amount (mg) of Fluorouracil RS
AT
AS
Proceed as directed in the Operating conditions under Fluorouracil Injection.
Method of Preparation Prepare as directed under Injections, with Fluorouracil by adding sodium hydroxide.
Description Fluorouracil Injection is a colorless, clear
liquid.
Identification (1) The retention time of the major peak
in the chromatogram of the Assay preparation corresponds to that of the standard preparation, both relative to
the internal standard, as obtained in the Assay.
(2) Measure a volume of Fluorouracil Injection,
equivalent to about 0.1 g of Fluorouracil according to the
labeled amount, acidify with glacial acetic acid carefully,
shake and precipitate the Fluorouracil. Collect the precipitate, wash with 1 mL of water and dry in vacuum over
P2O5 at 80 C for 4 hours. Determine the infrared spectra
of the precipitate and fluorouracil RS, respectively, as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Proceed as directed in the Identification (1) under Fluorouracil.
Bacterial Endotoxins Less than 0.33 Endotoxin unit
per mg of Fluorouracil.
It
Determination of Volume of Injection in Container

Assay Measure exactly a volume of Fluorouracil Injection, equivalent to about 50 mg of fluorouracil
(C4H3FN2O2) according to the labeled amount and add
water to make 100 mL. Pipet 5.0 mL of this solution, add
water to make 250 mL and use this solution as the test
fluorouracil RS, previously dried, dissolve in water to
make 100 mL, pipet 5.0 mL of this solution, add water to
make 50 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution
Chromatography according to the following conditions:
determine the peak areas, AT and AS , of Fluorouracil


(2) A solution of Fluoxetine Hydrochloride (1 in 50)
uid responds to the Qualitative Tests for chloride.
Amount (mg) of fluorouracil (C4H3FN2O2)
Purity (1) Heavy metalsProceed with l.0 g of Fluoxetine Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of
Standard Lead Solution (not more than 30 ppm).
(2) Related substancesDissolve about 56 mg of
Fluoxetine Hydrochloride, accurately weighed, in the
mobile phase to make exactly 10 mL and use this solution as the test solution (1). To exactly 2 mL of the test
solution (1), add the mobile phase to make exactly 10
mL and use this solution as the test solution (2). Perform
the test with 10 L each of the test solution (1) and the
test solution (2) as directed under the Liquid Chromatography according to the following conditions. Measure
the area of the peak corresponding to fluoxetine related
substance I {N-methyl-3-pheny-[(,,-(trufluoro-mtolyl)oxy)propylamine hydrochloride], AT and the area of
peak of fluoxetine, AU, from the test solution (2) and calculate the area of peak of each related substances, Ai, and
total area of peaks of related substances excelpt the principal peak form the test solution (1): the amount of the
fluoxetine related substance I is not more than 0.15%, the
amount of -[2-(methylamino)ethyl]benzenemethanol is
not more than 0.25%, the amount of the fluoxetine related substance II {N-methyl-3-phenylpropylamine} is
not more than 0.25% and the total amount of related substances is not more than 0.5%.
A
= amount (mg) of Fluorouracil RS T 5
AS
Mobile phase: Water.
System suitability
with the standard solution, as directed under the above
operating conditions, theoretical plate number being not
less than 2500.
times and the relative standard deviation of the ratio of
the peak area is not more than 2.0%.
hermetic containers. Store at a dark place and avoid
freezing.
Fluoxetine Hydrochloride
O
H
N
CH3
H
F3C
HCl
C17H17F3NOHCl : 344.78
Fluoxetine Hydrochloride contains not less than 98.0%
and not more than 102.0% of fluoxetine hydrochloride
(C17H17F3NOHCl), calculated on the anhydrous basis.
Description Fluoxetine Hydrochloride is a white, crystalline powder.
Fluoxetine Hydrochloride is freely soluble in ethanol or
in methanol, sparingly soluble in dichloromethane, and
practically insoluble in diethyl ether.
spectra of Fluoxetine Hydrochloride and Fluoxetine Hydrochloride RS, previously dried, as directed in the potassiumn bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Amount (%) of fluoxetine related substance I

AT
= 100
AT + AU
Amount (%) of each related substance
= 100
Ai
AS + 5 AU
base-deactivated octylsilanized silica gel for liquid
Mobile phase: A mixture of the triethylamine buffer,
stabilizer-free tetrahydrofuran, and methanol (6 : 3 : 1).
System suitability
System performance: Dissolve about 22 mg of
Fluoxetine Hydrochloride RS, accurately weighed, in 10
mL of 1 mol/L sulfuric acid TS, heat at 80 C for 3 hours,
cool and transfer 0.4 mL of this solution to a 25-mL volumetric flask. Add 28 mg of Fluoxetine Hydrochloride
RS, 1 mg of fluoxetine related substance I and 1 mg of
fluoxetine related substance II, and add the mobile phase
to make exactly 25 mL. When the procedure is run with
KP 9 429
10 L of this solution under the above operating conditions, relative retention times of -[2-(methylamino)
ethyl]benzenemethanol, fluoxetine related substance II,
fluoxetine related substance I, fluoxetine and 4trifluoromethylphenol are about 0.24, 0.27, 0.94, 1.0 and
2.17, respectively, and the ratio of the height of the fluoxetine related substance I peak to the depth of the valley
between the fluoxetine and fluoxetine related substance I
peaks measured from the fluoxetine related substance I
peak height is not more than 1.1.
Time span of measurement: Three times as long as
the retention time of Fosfestrol.
Triethylamine bufferAdd 10 mL of triethylamine to
980 mL of water and adjust to a pH of 6.0 with phosphoric acid.
direct titration).
Assay Dissolve about 10 mg each of Fluoxetine Hydrochloride and Fluoxetine Hydrochloride RS, accurately
weighed, in the mobile phase to make exactly 100 mL
the following conditions, and measure the areas of the
pricipal peaks obtained from each solutions, AT and AS .
Amount (mg) of fluoxetine hydrochloride

(C17H17F3NOHCl) = amount (mg) of
Fluoxetine Hydrochloride RS
AT
AS
base-deactivated octylsilanized silica gel for liquid
Mobile phase: A mixture of the triethylamine buffer,
stabilizer-free tetrahydrofuran, and methanol (6 : 3 : 1).
System suitability
with 10 L of the standard solution under the above operating conditions, the symmetry factor of the fluoxetine
peak is not more than 2.0.
System reapetibility: When the test is repeated 6
above operating conditions, the relative standard deviation of the peak area of fluoxetine is not more than 2.0%.
Triethylamine bufferAdd 10 mL of triethylamine
to 980 mL of water and adjust to a pH of 6.0 with phos-
phoric acid.
Fluoxymesterone
H3C
H
HO
H3C
CH3
OH
C20H29FO3: 336.44
Fluoxymesterone, when dried, contains not less than
97.0% and not more than 102.0% of fluoxymesterone
(C20H29FO3).
Description Fluoxymesterone is a white crystal or
crystalline powder. Fluoxymesterone is odorless.
Fluoxymesterone is sparingly soluble in methanol,
slightly soluble in ethanol or chloroform, very slightly
soluble in ether, and practically insoluble in water.
Identification (1) Dissolve 5 mg of Fluoxymesterone
in 2 mL of sulfuric acid: a yellow color is observed.
(2) Prepare the test solution with 10 mg of Fluoxymesterone as directed under the Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L
sodium hydroxide TS and 20 mL of water as an absorbing liquid: the test solution responds to the Qualitative
Tests (2) for fluoride.
Fluoxymesterone and Fluoxymesterone RS, respectively,
in ethanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(4) Determine the infrared spectra of Fluoxymesterone and Fluoxymesterone RS, previously dried, as directed in the potassium bromide disk method under the
exhibit the similar intensity of absorption at the same
wavenumbers. If any difference appears in the absorption
spectra, dissolve the test and the references standard in
dehydrated ethanol, respectively, evaporate the dehydrated ethanol and perform the test with the residue in
the same manner.
+112 (after drying, 0.1 g, ethanol, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 0.5 g of Fluoxymesterone according to Method 2 and perform the test.
(2) Related substancesDissolve 30 mg of Fluo-

xymesterone in 10 mL of methanol and use this solution
as the test solution. Pipet exactly 1 mL of the test solution, add methanol to make exactly 100 mL and use this
the test solution and the standard solution as directed under the Thin-layer chromatography. Spot 10 L each of
silica gel with fluorescent indicator for Thin-layer chromatography. Develop the plate with a mixture of toluene,
ethanol and ethyl acetate (3 : 1 : 1) to a distance of about
hours).
Assay Weigh accurately about 25 mg each of Fluoxymesterone and Fluoxymesterone RS, previously dried,
dissolve each in the internal standard solution to make
exactly 100 mL and use these solutions as the test solution and the standard solution, respectively. Perform the
ratios, QT and QS , of the peak area of Fluoxymesterone to that of the internal standard for the test solution
Amount (mg) of fluoxymesterone (C20H29FO3)

= amount (mg) of Fluoxymesterone RS
QT
QS
Internal standard solutionA solution of methylprednisolone in a mixture of chloroform and methanol

(19 : 1) (1 in 5000).
silica gel for liquid chromatography (5 m in particle diameter).
about 25 o C .
Mobile phase: A mixture of n-butyl chloride, watersaturated n-butyl chloride, tetrahydrofuran, methanol and
glacial acetic acid (95 : 95 : 14 : 7 : 6).
time of Fluoxymesterone is about 9 minutes.
System suitability
above operating conditions, fluoxymesterone and the internal standard are eluted in this order with a resolution
between their peaks being not less than 6.
under the above operating conditions, the relative deviation of the peak area of fluoxymesterone is not more than
1.5%.
Fluoxymesterone Tablets
Fluoxymesterone Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of fluoxymesterone (C20H29FO3: 336.44).
Method of Preparation Prepare as directed under Tablets, with Fluoxymesterone.
Identification Weigh equivalent to about 20 mg of fluoxymesterone (C20H29FO3) to a portion of powdered
Fluoxymesterone Tablets, add 20 mL of hot chloroform,
shake and decant the supernatant clear liquid through a
filter. Repeat the extraction with two 20 mL volumes of
hot chloroform, combine the extracts, evaporate on the
water-bath to dryness, dissolve the residue in 5 mL of
acetone, decant the supernatant liquid and filter the precipitate produced after adding 20 mL of water. Dissolve
the precipitate in 5 mL of acetone and filter the precipitate produced after adding 20 mL of water. Perform the
test with the precipitate, dried at 105 C for 3 hours, as
directed in the Identification (4) under Fluoxymesterone.
Dissolution Test Perform the test with 1 tablet of Fluoxymesterone Tablets at 75 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of 0.10 mol/L hydrochloric acid. Take the dissolved solution after 60 minutes from starting of the test,
filter, take 20 mL of the filtrate, add 2.0 mL of the internal standard solution and 0.10 mol/L of hydrochloric acid to make exactly 25 mL and use this solution as the test
Fluoxymesterone RS, previously dried at 105 C for 3
hours and add ethanol to make exactly 25 mL. Pipet exactly 5 mL of this solution, add 2.0 mL of the internal
standard solution exactly, add 0.10 mol/L hydrochloric
acid to make exactly 25 mL and use this solution as the
the test solution and the standard solution as directed under Liquid Chromatography according to the following
peak area of Fluoxymesterone to that of the internal
respectively.
The dissolution rate of Fluoxymesterone Tablets in 60
KP 9 431
minutes is not less than 70%.
Fluphenazine Enanthate
Internal standard solutionA solution of Norethindrone in ethanol (4.6 in 100000).
O
CH2CH2CH2
(58 : 42).
System suitability
above operating conditions, Fluoxymesterone and norethindrone are eluted in this order with the resolution between their peaks being not less than 2.0.
times with 20L of the standard solution, as directed under the above operating conditions, the relative standard
deviation of the ratio of the peak area is not more than
2.0%.
of the Content Uniformity Test when the test is performed according to the following method. Transfer 1
Fluoxymesterone Tablets to a suitable container, add 2
mL of water and sonicate for about 30 minutes until the
tablet completely disintegrates. Add the internal standard
solution to obtain a solution having a known concentration of 250 g per mL of fluoxymesterone (C20H29FO3)
and proceed as directed in the Assay under Fluoxymesterone.
Fluoxymesterone Tablets. Weigh accurately a portion of
the powder, equivalent to about 5 mg of fluoxymesterone
(C20H29FO3), add 20 mL of the internal standard solution.
Sonicate for 10 minutes and mix for 15 minutes. Filter
this solution and use this solution as the test solution.
Proceed as directed in the Assay under Fluoxymesterone.
Amount (mg) of fluoxymesterone (C20H29FO3)

= amount (mg) of Fluoxymesterone RS
QT
QS
CH2CH2O
(CH2)5CH3
N
CF3
C29H38F3N3O2S: 549.69
Fluphenazine Enanthate, when dried, contains not less
than 98.5% and not more than 101.0% of fluphenazine
enanthate (C29H38F3N3O2S).
Description Fluphenazine Enanthate is a pale yellow
to yellowish orange, viscous liquid. Fluphenazine Enanthate is generally clear and can be opaque by producing
crystal.
Fluphenazine Enanthate is freely soluble in methanol or
ether, soluble in glacial acetic acid or ethanol, and practically insoluble in water.
Identification (1) Prepare the test solution with 10 mg
of Fluphenazine Enanthate as directed under the Oxygen
Flask Combustion Method, using a mixture of 0.5 mL of
0.01 mol/L sodium hydroxide TS and 20 mL of water as
the absorbing liquid: the test solution responds to the
Qualitative Tests for fluoride.
(2) Dissolve 2 mg each of Fluphenazine Enanthate
and Fluphenazine Enanthate RS separately in 200 mL of
a solution of hydrochloric acid in methanol (17 in 2000)
and determine the absorption spectra as directed under
the Ultraviolet-visible Spectrophotometry, respectively:
(3) Determine the infrared spectra of Fluphenazine
Enanthate and Fluphenazine Enanthate RS as directed in
the liquid method under the Infrared Spectrophotometry,
Purity (1) Heavy metalsProceed with 1.0 g of Fluphenazine Enanthate according to Method 2 and perform
(2) Related substancesDissolve 0.25 g of Fluphenazine Enanthate in 10 mL of methanol and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add methanol to make exactly 100 mL and use
of acetone, hexane and strong ammonia water (16 : 6 : 1)
to a distance of about 15 cm and air-dry the plate. Ex-

amine under ultraviolet light (main wavelength: 254 nm):
any spot other than the principal spot from the test solution is not more intense than the spot from the standard
solution. Then spray evenly diluted sulfuric acid (1 in 2)
on the plate: the spots other than the principal spot from
60 C, 3 hours).
Assay Weigh accurately about 0.5 g of Fluphenazine
Enanthate, previously dried, dissolve in 50 mL of glacial
(indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.

= 27.485 mg of C29H38F3N3O2S
tight containers.
Fluphenazine Hydrochloride
CH2CH2CH2
N
CH2CH2OH
2 HCl
CF3
C22H26F3N3OS2HCl: 510.44
Fluphenazine Hydrochloride contains not less than
97.0% and not more than 103.0% of fluphenazine hydrochloride (C22H26F3N3OS2HCl), calculated on the
dried basis.
Description Fluphenazine Hydrochloride is a white or
nearly white crystalline powder and has no odor.
Fluphenazine Hydrochloride is freely soluble in water,
sparingly soluble in acetone, ethanol or chloroform, and
practically insoluble in benzene or ether.
Melting point225 C.
Identification (1) The ultraviolet-visible absorption
spectrum of a solution of Fluphenazine Hydrochloride in
methanol (1 in 100000) exhibits maxima and minima at
the same wavelengths as that of a similar preparation of
Fluphenazine Hydrochloride RS, concomitantly measured and the respective absorbance, calculated on the
dried basis, at the wavelength of a maximum absorbance
at about 259 nm do not differ by more than 2.5%.
(2) Determine the infrared spectra of Fluphenazine

Hydrochloride and Fluphenazine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
method under the Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Fluphenazine Hydrochloride responds to the Qualitative Tests for chloride.
Purity (1) Heavy metalsWeigh about 1.0 g of Fluphenazine Hydrochloride and perform a test according to
the Method 2. The control solution contains 3.0 mL of
(2) Related substancesDissolve about 0.1 g of
Fluphenazine Hydrochloride in a mixture of Sodium Hydroxide and methanol to make 10 mL and use this solution as the test solution. Separately, dissolve 10 mg of
Fluphenazine Hydrochloride RS in a mixture of Sodium
Hydroxide and methanol to make 10 mL. Pipet exactly
0.1 mL, 0.5 mL, 1 mL and 2 mL of test solution, add sodium hydroxide and methanol to make exactly 10 mL
and use this solution as the standard solution (1), standard solution (2), standard solution (3), standard solution
(4). Perform the test with the test solution and the standard solutions as directed under the Thin-layer chromatography. Spot 20 L each of the test solution and the
standard solution (1), standard solution (2), standard solution (3), standard solution (4) on a plate of silica gel
Develop the plate with a mixture of acetone, hexane and
strong ammonia water (40 : 15 : 1) to a distance of about
light (main wavelength: 254 nm): prepare intensities of
the spots other than the principal spot from the test solution and the spot from the standard solutions, the relative
intensities is not less than 2.0%.
hours).
Residue on Ignition
Assay Dissolve about 0.12 g of Fluphenazine Hydrochloride, accurately weighed, in a mobile phase without triethylamine to make 100 mL exactly. Pipet exactly 5 mL
of this solution, dilute in mobile phase without triethylamine to make 100 mL exactly. Filter and use this solution
as the test solution. Separately, dissolve about 0.12 g of
Fluphenazine Hydrochloride RS, accurately weighed, in
a mobile phase without triethylamine to make 100 mL
exactly. Pipet exactly 5 mL of this solution, dilute in mobile phase without triethylamine to make 100 mL exactly.
Filter and use this solution as the standard solution. Perform the test with 25 L each of the test solution and the
standard solution as directed under Liquid Chromatography according to the following conditions and calculate
the ratios, AT and AS , of the peak area of fluphenazine.
KP 9 433
Amount (mg) of fluphenazine hydrochloride
(C22H26F3N3OS) = amount (mg) of Fluphenazine Hydrochloride RS
AT
AS
Column: A stainless steel column, about 4 mm in inside diameter and about 12.5 cm in length, having octadecylsilanized silica gel for liquid chromatography (3
Mobile phase: Filter a mixture of 0.05 mol/L of potassium dihydrogen phosphoric acid (controlled by phosphoric acid to pH 2.5), acetonitrile and methanol (40 :
30 : 30) and add triethylamine to make 0.2%.
System suitability
System performance: When the procedure is run with 25
L of the standard solution, as directed under the above
operating conditions, symmetry coefficient is not less
than 2.0.
times with 25 L of the standard solution and the relative
standard deviation of the ratio of the peak area is not
more than 2.0%.
tight containers.
Fluphenazine Hydrochloride
Tablets
Fluphenazine Hydrochloride Tablets contain not less than
of fluphenazine hydrochloride (C22H26F3N3OS2HCl:
510.44).
Method of Preparation Prepare as directed under Tablets, with Fluphenazine Hydrochloride.
Identification Transfer a portion of finely powdered
Tablets, equivalent to about 10 mg of Fluphenazine Hydrochloride according to the labeled amount, and 10 mg
of Fluphenazine Hydrochloride RS separately into two
separators. Add 5 mL of water and 20 mL of diluted hydrochloric acid (1 in 120) to each separator, shake for 10
minutes and to each mixture, add 20 mL of chloroform
saturated with sodium carbonate solution (1 in 10). Extracts each mixture with five 20 mL volumes of chloroform-washed cotton filters into separate beakers. Evaporate the extracts on a steam-bath to dryness and dissolve
the residues separately in 0.5 mL of a mixture of methanol and water (4 : 1) and use the solutions as the test solution and the standard solution. Perform the test with the

with a mixture of acetone, cyclohexane, diethylamine
plate. Spray evenly on the plate with a solution of sulfuric acid in methanol (2 in 5): the Rf value and color of
the principal spot obtained from the test solution correspond to those obtained from the standard solution.
Dissolution Test Perform the test with 1 tablet of Fluphenazine Hydrochloride Tablets at 100 revolutions per
using 900 mL of 0.01 mol/L hydrochloric acid VS. Take
the dissolved solution after 45 minutes from the start of
the test and perform the Assay with following differences: dilute the amount of the test solution to be withdrawn
with an equal volume of mobile phase without triethylamine; inject a volume of 100 L, in the Standard preparation, use a concentration and composition similar to
that of the test solution; in the Mobile phase, use 0.3%
triethylamine; in the Chromatographic system, use a flow
rate of about 2.0 mL per minute.
The dissolution rate of Fluphenazine Hydrochloride Tablets in 45 minutes should be not less than 75%.
Assay Weigh and finely powder not less than 20 Fluphenazine Hydrochloride Tablets. Transfer an accurately
weighed portion of the powder, equivalent to about 6 mg
of Fluphenazine Hydrochloride, to a separator, add 80
mL of mobile phase without triethylamine, shake well
for 1 hour. Then sonicate for 10 minutes to make a fine
colloid solution. Filter and use this solution test solution.
Separately, place about 6 mg of Fluphenazine Hydrochloride RS, accurately weighed to a volumetric flask, add
mobile phase without triethylamine to dissolve and make
100 mL exactly and use this solution as the standard solution. Separately inject equal volumes (about 25 L) of
the test solution and standard solution and determine the
absorbances of the solutions as directed under the Liquid
Chromatographic method, calculate the absorbances,
AT and AS , for the test solution and the standard solution, respectively.
Amount (mg) of fluphenazine (C22H26F3N3OS2HCl) =

amount (mg) of Fluphenazine Hydrochloride RS
AT
AS
and system suitability conform to the requirements of
Fluphenazine Hydrochloride in the Requirements for operating conditions of Assay.
Flurazepam
C2H5
CH2CH2N
O
N
Cl
C2H5
N
F
C21H23ClFN3O: 387.88
Flurazepam, when dried, contains not less than 99.0%
and not more than 101.0% of flurazepam
(C21H23ClFN3O).
Description Flurazepam occurs as white to pale yellow
crystals or crystalline powder.
Flurazepam is very soluble in chlorform, freely soluble
in methanol, in ethanol, in acetic anhydride, or in ether
Identification (1) Dissolve 0.01 g of Flurazepam in 3
mL of sulfuric acid: the solution shows a greenish yellow
flurescence under ultraviolet light (main wavelength: 365
nm).
(2) Dissolve 0.01 g of Flurazepam in 3 mL of citric
acid acetic acid TS and heat in a water-bath for 4 minutes: a dark red color develops.
(3) Prepare the test solution with 0.01 g of Flurazepam as directed under the Oxygen Flask Combustion
the test solution responds to the Qualitative Tests (2) for
fluoride.
of Flurazepam and Flurazepam RS in methanol (1 in
absorption at the same wavelengths. And determine the
spectra of the solutions of Flurazepam and Flurazepam
RS in methanol (1 in 10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
similar intensities of absorption at the same wavelengths
(5) Perform the test with Flurazepam as directed under the Flame Coloration Test (2): a green color appears.
Purity (1) Clarity and color of solutionDissolve 1.0 g
of Flurazepam in 10 mL of ethanol: the solution is clear
and colorless to pale yellow.
(2) Chloride Dissolve 1.0 g of Flurazepam in 50
mL of ether, add 46 mL of water and 4 mL of sodium
carbonate TS, shake, separate the water layer, wash with
two 20-mL volumes of ether and filter the water layer.
Neutralize 20 mL of the filtrate with dilute nitric acid and

add 6 mL of dilute nitric acid and water to make 50 mL.
hydrochloric acid VS (not more than 0.036%)
(3) SulfateNeurtralize 20 mL of the filtrate obtained in (2) with dilute hydrochloric acid and add 1 mL
of dilute hydrochloric acid and water to make 50 mL.
(4) Heavy metalsProceed with 2.0 g of Flurazepam
Flurazepam according to Method 3 and perform the test
(6) Related substancesDissolve 0.20 g of Flurazepam in 20 mL of chloroform and use this solution as the
chloroform to make exactly 20 mL. Pipet 3.0 mL of this
solution, add chloroform to make exactly 50 mL and use
plate of silica gel with flurescence indicator for Thinlayer chromatography. Develop the plate with a mixture
of cyclohexane, acetone and strong ammonia water (60 :
Examine under the ultraviolet light (main wavelength:
254 nm): the spots other than the principal spot from the
standard solution.
60 C, 2 hours).
Assay Weigh accurately 0.3 g of Flurazepam, previously dried, dissolve in 50 mL of acetic anhydride and titrate
with 0.1 mol/L perchloric acid VS to the second equivalence point (potentiometric titration, Endpoint Detection
Method in Titrimetry). Perform a blank determination

= 19.394 mg of C21H23ClFN3O
KP 9 435
Flurazepam Capsules
Flurazepam Hydrochloride
C2H5
Flurazepam Capsules contain not less than 93.0% and

not more than 107.0% of the labeled amount of flurazepam (C21H23ClFN3O: 387.88).
Capsules, with Flurazepam.
Identification (1) Powder the contents of Flurazepam
Capsules. To a quantity of the powder, equivalent to 0.1
g of Flurazepam according to the labeled amount, add
100 mL of 0.1 mol/L hydrochloric acid TS, stir and filter.
To 40 mL of the filtrate, add 80 mL of a solution of sodium hydroxide (1 in 250) and 100 mL of hexane, extract
by shaking well and use the hexane layer as the test solution. Evaporate 25 mL of the test solution on a waterbath to dryness. Dissolve the residue in 3 mL of sulfuric
acid: the solution shows a greenish yellow fluorescence
under ultraviolet light.
(2) Evaporate 25 mL of the test solution obtained in
(1) on a water-bath to dryness. Dissolve the residue in 3
mL of citric acid-acetic acid TS and heat in a water-bath
for 4 minutes: a dark red color develops.
(3) Determine the absorption spectrum of the test solution obtained in the Assay as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum
between 315 nm and 319 nm and a minimum between
297 nm and 301 nm.
20 Flurazepam Capsules and powder the combined contents. Weigh accurately a portion of the powder, equivalent to about 0.05 g of flurazepam (C21H23ClFN3O), add
30 mL of methanol, stir well for 10 minutes and add methanol to make exactly 50 mL. Filter this solution, discard the first 20 mL of the filtrate, pipet 6.0 mL of the
subsequent filtrate, add methanol to make exactly 50 mL
weigh accurately about 0.05 g of Flurazepam RS, previously dried in vacuum at 60 C for 2 hours and dissolve
in methanol to make exactly 50 mL. Pipet 6.0 mL of this
this solution as the standard solution. Determine the absorbances, AT and AS , of test solution and the standard solution at 317 nm as directed under the Ultravioletvisible Spectrophotometry, respectively.
Amount (mg) of flurazepam (C21H23ClFN3O)

= amount (mg) of Flurazepam RS
AT
AS
CH2CH2N
O
N
Cl
C2H5
HCl
F
C21H23ClFN3OHCl: 424.34
Flurazepam Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of flurazepam hydrochloride (C21H23ClFN3OHCl).
Description Flurazepam Hydrochloride occurs as a
white to yellowish white crystal or crystalline powder.
Flurazepam Hydrochloride is freely soluble in water, in
ethanol, in dehydrated ethanol, or in glacial acetic acid.
the solutions of Flurazepam Hydrochloride and Flurazepam Hydrochloride RS in sulfuric acid ethanol TS (1 in
100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibits similar intensities of
(2) Determine the infrared spectrum of Flurazepam
Hydrochloride and Flurazepam Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Flurazepam Hydrochloride (1 in 20)
pH Dissolve 1.0 g of Flurazepam Hydrochloride in 20
6.0.
g of Flurazepam Hydrochloride in 10 mL of water: the
solution is clear and colorless to pale yellow.
(2) SulfatePerform the test with 1.5 g of Flurazepam Hydrochloride. Prepare the control solution with
0.011%).
(3) Heavy metalsProceed with 1.0 g of Flurazepam
Hydrochloride in a platinum crucible according to Method 2 and perform the test. Prepare the control solution
with 2.0 mL of standard lead solution (not more than 20
ppm).
(4) Related substancesDissolve 50 mg of Flurazepam Hydrochloride in 5 mL of ethanol and use this solu-

tion as the test solution. Pipet 1.0 mL of this solution,
add ethanol to make exactly 10 mL and use this solution
as the standard solution. Perform the test with the test
and standard solutions as directed under the Thin-layer
the standard solution on a plate of silica gel with fluorescent indicator for Thin-layer chromatography. Place the
plate in a chamber filled with ammonia vapor, allow to
stand for about 15 minutes and immediately develop the
plate with a mixture of ether and diethylamine (39 : 1) to
a distance of about 12 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm): not
more than 3 spots other than the principal spot and the
spot on the starting point from the test solution appear
and are not more intense than the spot from the standard
solution
hours).
Residue on Ignition
Assay Weigh accurately about 0.3 g of Flurazepam

glacial acetic acid, add 40 mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid VS (potentiometric

= 21.217 mg of C21H23ClFN3OHCl
Flurbiprofen
H
CH3
F
CO2H
and enantiomer
C15H13FO2: 244.26
Flurbiprofen, when dried, contains not less than 98.0%
and not more than 101.0% of flurbiprofen (C15H13FO2).
Description Flurbiprofen is a white, crystalline powder
and has a slightly irritating odor.
Flurbiprofen is freely soluble in methanol, in ethanol, in
acetone or in ether, soluble in acetonitrile and practically
insoluble in water.
A solution of Flurbiprofen in ethanol (1 in 50) shows no
optical rotation.

the solutions of Flurbiprofen and Flurbiprofen in methanol (1 in 200000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectrum of Flurbiprofen
and Flurbiprofen RS, previously dried, as directed in the
Purity (1) ChlorideDissolve 0.6 g of Flurbiprofen in
40 mL of acetone and add 6 mL of dilute nitric acid and
as the test solution. Prepare the control solution as follows: to 0.25 mL of 0.01 mol/L hydrochloric acid VS,
(2) Heavy metalsDissolve 2.0 g of Flurbiprofen in
30 mL of acetone and add 2 mL of dilute acetic acid and
as the test solution. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 30 mL of
acetone, add 2 mL of dilute acetic acid and water to
(3) Related substances-Dissolve 20 mg of Flurbiprofen in 10 mL of a mixture of water and acetonitrile (11 :
of the test solution and add a mixture of water and acetonitrile (11:9) to make exactly 200 mL and use this solution as the standard solution. Perform the test with 20 L
the test solution and the standard solution by the automatic integration method: each area of the peaks other
than the peak of Flurbiprofen from the test solution is not
larger than the peak area of Flurbiprofen from the standard solution and the total area of these peaks is not larger than twice the peak area of Flurbiprofen from the
standard solution.
about 30 C.
time of Flurbiprofen is about 20 minutes.
System suitability
KP 9 437
the standard solution, add a mixture of water and acetonitrile (11:9) to make exactly 25 mL. Confirm that the
peak area of flurbiprofen from 20 L of this solution is
equivalent to 16 to 24% of that of flurbiprofen from 20
System performance: Dissolve 0.04 g of flurbiprofen and 0.02 g of butyl parahydroxybenzoate in 100 mL
of a mixture of water and acetonitrile (11:9). To 5 mL of
this solution, add a mixture of water and acetonitrile
(11:9) to make 50 mL. When the procedure is run with
20 L of this solution under the above operating conditions, butyl parahydroxybenzoate and flurbiprofen are
above operating conditions, the relative standard deviation of the peak area of flurbiprofen is not more than
2.0%.
the retention time of Flurbiprofen.
at a pressure not exceeding 0.67 kPa, silica gel, 4 hours).
Assay Weigh accurately about 0.6 g of Flurbiprofen,
previously dried, dissolve in 50 mL of ethanol and titrate
with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops
of phenolphthalein TS). Perform a blank determination

= 24.426 mg of C15H13FO2
Fluticasone Propionate
F
O
CH3
HO
CH3
CH3
(C25H31F3O5S), calculated on the anhydrous and soventfree basis.

Description Fluticasone Propionate is as a white, fine
powder.
Fluticasone Propionate is sparingly soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water.
spectra of Fluticasone Propionate and Fluticasone Propionate RS as directed in the paste method under the
(2) The retention time of the principal peak from the
test solution is same as that from the standard solution
obtained in the Assay.
D : Between +32 and
+36 (calculated on the anhydrous and solvent-free basis,
0.1 g, dichloromethane, 20 mL, 100 mm).
Purity (1) Related substancesDissolve 20 mg of
Fluticasone Propionate in 5.0 mL of the mobile phase A
by sonication, add 5.0 mL of the mobile phase C and use
this solution as the test solution. Perform the test with 50
L of the test solution as directed in the area percentage
method under the Liquid Chromatography according to
the following conditions, and measure the area of each
realted substance and the total area of all of the related
substances, Ai and AS : the limit of the related substances are as shown in Table I.
Table 1
Related substances
Relative retention time
Limit (%)
Fluticasone propionate re0.5

0.2
lated substance I
0.1
lated substance II
0.1
lated substance III
0.3
lated substance IV
Fluticasone propionate
1.0
0.3
lated substance V
Other related substances
0.1
Total related substances
1.0
Any related substances of less than 0.5% are disregarded
from the total amount of related substances.
Ai
Amount(%) of each related substance = 100 A
S
C25H31F3O5S : 500.57
Fluticasone Propionate contains not less than 98.0% and
not more than 100.5% of fluticasone propionate

about 40 C.
Control the gradient by mixing the mobile phases A,
B and C as directed in the following table.
Mobile phase A: Mix 0.5 mL of phosphoric acid
with 1000 mL of acetonitrile
Mobile phase B: Mix 0.5 mL of phosphoric acid
with 1000 mL of methanol
Mobile phase C: Mix 0.5 mL of phosphoric acid
with 1000 mL of water
Table 2
Time after
injection
(minutes)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
Mobile
phase C
(vol%)
42
55
0 to 40
42 53
55 44
40 to 60
53 87
44 10
60 to 70
87
10
70 to 75
87 42
10 55
Elution
condition
Equalibriation
Linear
gradient
Linear
gradient
Isocratic
Reequalibriation

System suitability
System performance: Weigh about 2.0 mg og fluticasone propionate in 5.0 mL of the mobile phase A by
sonication, add 5.0 mL of the mobile phase C and use
this solution as the system suitability solution. When the
procedure is performed with 50 L of this solution accoding to the above operating conditions, the resolution
between peaks of fluticasone propionate related substance II and fluticasone propionate related substance III
is not less than 1.5 and their relative retion times are as
shown in Table I.
(2) BromofluoromethaneDissolve 0.2 g of Fluticasone Propionate in 1 mL of dimethylformamide and use
this solution as the test solution. Separately, measure 20
L of bromofluoromethane, add dimethylformamide to
make 10 mL, take 10 L of this solution, and add dimethylformamide to make 1 mL. Take 10 L of this solution, add dimethylformamide to make 1 mL, and use this
directed under Gas Chromatography according to the following conditions, and determine heights of peaks of
bromofluoromethane: the height of the bromofluoromethane obtained from the test solution is less than that
Detector : An electron capture detector.
Column : A capillary column, about 0.35 mm in inside diameter and about 25 m in length, coated with 5%
phenyl-95% methylpolysiloxane with the thickness of 5
m.
Column temperature: Initially the temperature of the
column is maintained at 40 C for 3.5 minutes, then the
temperature is increased at a rate of 30 C per minute to
200 C, and maintained at 200 C for 10 minutes.
Inlet temperature: 85 C
Split ratio: about 70 : 1
(3) AcetoneDissolve 0.5 g of Fluticasone Propionate, accurately weighed, in the internal standard solution to make exactly 10 mL and use this solution as the
test solution. Separately, take exactly 50 L of acetone,
add the internal standard solution to make exactly 100
mL and use this solution as the standard solution. Perform the test with 0.1 L each of the test solution and the
standard solution as directed under Gas Chromatography
ratios, QT and QS, of the peak height of acetone to that of
the internal standard, for the test solution and the standard solution, respectively. (not more than 1.0%)
QT
D
Amount (%) of acetone = 0.05 C Q
S
D: density of acetone at 20 C
C: concentration (g/mL) of Fluticasone Propionate in
the test solution
Internal standard solutionTo 50 L of tetrahydrofuran, add dimethylformamide to make 100 mL.
Detector : A hydrogen flame ionization detector.
Column : A capillary column, about 0.53 mm in inside diameter and about 25 m in length, coated with polyethylene glycol (mean molecular mass is between 3000
and 3700) with the thickness of 2 m.
Column temperature: Initially the temperature of the
column is maintained at 60 C for 3.5 minutes, then the
temperature is increased at a rate of 30 C per minute to
180 C, and maintained at 180 for 3 minutes.
Carrier gas: Nitrogen or helium
Inlet temperature: 150 C
System suitability
times with 0.1 L of the standard solution under the
above operating conditions, the relative standard deviation of the peak height of acetone is not more than 5.0%.
KP 9 439
direct titration).
Assay Dissolve about 40 mg each of Fluticasone Propionate and Fluticasone Propionate RS, accurately
weighed, in the mobile phase to make exactly 100 mL.
Pipet exactly 5 mL of this solution and add the mobile
phase to make exactly 50 mL and use these solutions as
measure the areas of fluticasone propionate obtained
from each solutions, AT and AS .
Amount (mg) of fluticasone propionate

(C25H31F3O5S) = amount (mg) of
A
Fluticasone Propionate RS T
AS
about 40 C.
Mobile phase: A mixture of methanol, 0.01 mol/L
ammonium dihydrogen phosphate buffer, and acetonitrile (50 : 35 : 15).
System suitability
System performance: Dissolve 2.0 mg of fluticasone propionate related substance IV RS in 50 mL of the
mobile phase. When the procedure is run with 20 L
each of this solution and the standard solution under the
above operating conditions, relative retention times
peaks of fluticasone propionate related substance IV and
fluticasone propionate are 1.1 and 1.0, respectively, and
the resolution between them is not less than 1.5.
System reapetibility: When the test is repeated 6
above operating conditions, the relative standard deviation of the peak area of fluticasone propionate is not
more than 2.0%.
0.01 mol/L ammonium dihydrogen phosphate buffer
Dissolve 11.5 g of ammonium dihydrogen phosphate in
1000 mL of water and adjust to a pH of 3.5 0.05 with
phosphoric acid.
tight containers and store at the temperature of not more
than 30 C.
Folic Acid
O
OH
N
CH2NH
H
NH
CH2CH2CO2H
N
CO2H
H2N
C19H19N7O6: 441.40
Folic Acid, when dried, contains not less than 98.0% and
not more than 102.0% of folic acid (C19H19N7O6).
Description Folic Acid is a yellow to orange-yellow,
Folic Acid is practically insoluble in water, in methanol,
in ethanol, in pyridine or in ether.
Folic Acid dissolves in hydrochloric acid, in sulfuric acid,
in dilute sodium hydroxide TS or in a solution of sodium
carbonate (1 in 100) and these solutions are yellow in
color.
Folic Acid is affected gradually by light.
Identification (1) Dissolve 1.5 mg each of Folic Acid
and Folic Acid RS in dilute sodium hydroxide TS to
make 100 mL. Determine the absorption spectra of these
solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
(2) Take 10 mL of the solution obtained with Folic
Acid in (1), add 1 drop of potassium permanganate TS
and mix well until the color changes to blue and immediately observe under ultraviolet light (main wavelength:
365 nm): a blue fluorescence is produced.
0.10 g of Folic Acid in 10 mL of dilute sodium hydroxide
TS: the solution is clear and yellow in color.
(2) Free aminesPipet exactly 30 mL of the test solution obtained in the Assay, add 20 mL of dilute hydrochloric acid and water to make accurately 100 mL
and use this solution as the test solution. Weigh accurately about 50 mg of p-aminobenzoylglutamic acid RS, previously dried in a desicator (in vacuum, silica gel) for 4
hours, dissolve in diluted ethanol (2 in 5) to make exactly
100 mL. Pipet exactly 3 mL of this solution, add water to
make exactly 1000 mL and use this solution as the standard solution. Pipet exactly 4 mL each of the test solution and the standard solution, proceed as directed in the
Assay and perform the test as directed under the Ultraviolet-visible Spectrophotometry. Determine the absorbances, AT and AS, of the test solution and the standard
solution, respectively, at 550 nm: the content of free
amines is not more than 1.0%.
W'
AT
Content (%) of free amines = A W
S
W: Amount (mg) of Folic Acid, calculated on the an-

hydrous basis,
W: Amount (mg) of p-aminobenzoyl-glutamic acid
RS.
Water Not more than 8.5% (10 mg, coulometric titration).
Assay Weigh accurately about 50 mg each of Folic Acid and Folic Acid RS. To each, add 50 mL of dilute sodium hydroxide TS, mix well to dissolve, add dilute sodium hydroxide TS to make exactly 100 mL and use
these solutions as the test solution and the standard solution, respectively. To 30 mL each of the test solution and
the standard solution, accurately measured, add 20 mL of
dilute hydrochloric acid and water to make exactly 100
mL. Take 60 mL each of these solutions, add 0.5 g of
zinc powder and allow to stand with frequent shaking for
20 minutes. Filter each mixture through a dry filter paper
and discard the first 10 mL of the filtrate. Pipet exactly
10 mL each of the subsequent filtrate and add water to
make exactly 100 mL. To 4 mL each of solutions, accurately measured, add 1 mL of water, 1 mL of dilute hydrochloric acid and 1 mL of a solution of sodium nitrite
(1 in 1000), mix well and allow to stand for 2 minutes.
To each solution, add 1 mL of a solution of ammonium
sulfate (1 in 200), mix thoroughly and allow to stand for
2 minutes. To each of these solution, add 1 mL of a solution of N-(1-naphthyl)-N-diethylethlyen ediamine oxalate (1 in 1000), shake, allow to stand for 10 minutes and
add water to make exactly 20 mL. Separately, to 30 mL
of the test solution, accurately measured, add 20 mL of
dilute hydrochloric acid and water to make exactly 100
mL. Pipet exactly 10 mL of this solution and add 18 mL
of dilute hydrochloric acid and water to make exactly
100 mL. Pipet exactly 4 mL of this solution and prepare
the blank solution in the same manner as the test solution.
the Ultraviolet-visible Spectrophotometry, using a solution prepared with 4 mL of water in the same manner as
a blank. Determine the absorbances, AT, AS and AC, of the
test solution, the standard solution and the blank solution,
respectively, at 550 nm.
Amount (mg) of folic acid (C19H19N7O6)

= amount (mg) of Folic Acid RS,
AT - AC
S
tight containers.
Folic Acid Injection

Folic Acid Injection is an aqueous solution for injection.
Folic Acid Injection contains not less than 95.0% and not
more than 115.0% of the labeled amount of folic acid

(C19H19N7O6: 441.40).
Method of Preparation Dissolve Folic Acid in water
with the aid of Sodium Hydroxide or Sodium Carbonate
and prepare as directed under Injections.
Description Folic Acid Injection is a yellow to orangeyellow, clear liquid.
Identification (1) Take a volume of Folic Acid Injection, equivalent to 1.5 mg of folic acid according to the
labeled amount, add dilute sodium hydroxide TS to make
100 mL. Perform the test with this solution as directed in
the Identification (2) under Folic Acid.
(2) Perform the test with the solution obtained in (1) as
it exhibits maxima between 255 nm and 257 nm, between 281 nm and 285 nm, and between 361 nm and 369
nm and when A1 is the absorbance at the absorption maximum between 255 nm and 257 nm, and A2 is the absorbance at the absorption maximum between 361 nm and
369 nm, the ratio, A2/A1, is between 2.80 and 3.00.
(3) Folic Acid Injection responds to the Qualitative
Tests (1) for sodium salt.
It

Assay To an exactly measured volume of Folic Acid
Injection, equivalent to about 50 mg of folic acid
(C19H19N7O6: 441.40), add dilute sodium hydroxide TS
Folic Acid RS, dissolve in dilute sodium hydroxide TS to
make exactly 100 mL and use this solution as the standard solution. Proceed with 30 mL each of the test solution and the standard solution, exactly measured, as directed in the Assay under Folic Acid.
Amount (mg) of folic acid (C19H19N7O6)

AT - AC
S
KP 9 441
Folic Acid Tablets
Formoterol Fumarate Hydrate
Folic Acid Tablets contain not less than 90.0% and not
more than 115.0% of the labeled amount of folic acid
(C19H19N7O6: 441.40).
H
H
N
Identification (1) Take a portion of powdered Folic

Acid Tablets, equivalent to 1.5 mg of Folic Acid according to the labeled amount, add 100 mL of dilute sodium hydroxide TS, shake well and filter. Discard the
first 10 mL of the filtrate, use the subsequent filtrate as
the test solution and perform the test as directed in the
Identification (2) under Folic Acid.
(2) Perform the test with the solution obtained in (1) as
it exhibits maxima between 255 nm and 257 nm, between 281 nm and 285 nm, and between 361 nm and 369
nm and when A1 is the absorbance at the absorption maximum between 255 nm and 257 nm, and A2 is the absorbance at the absorption maximum between 361 nm and
369 nm, the ratio, A2/A1, is between 2.80 and 3.00.
Folic Acid Tablets. Weigh accurately a portion of the
powder, equivalent to about 50 mg of folic acid
(C19H19N7O6: 441.40). Add 50 mL of dilute sodium hydroxide TS, shake frequently, then filter into a volumetric
flask and wash with dilute sodium hydroxide TS. Take
the combined filtrate and washings, add dilute sodium
hydroxide TS to make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately
about 50 mg of Folic Acid RS, dissolve in dilute sodium
hydroxide TS to make exactly 100 mL and use this solution as the standard solution. Take 30 mL each of the test
solution and the standard solution, exactly measured and
proceed as directed in the Assay under Folic Acid.
Amount (mg) of Folic Acid (C19H19N7O6)

AT - AC
S
NHCHO
HO2C
H
C
2H2O
H
CH3O
Method of Preparation Prepare as directed under Tablets, with Folic Acid.
OH
CH3
OH
H
2
CO2H
(C19H24N2O4)2C4H4O42H2O: 840. 91
Formoterol Fumarate Hydrate contains not less than
98.5% and not more than 101.0% of formoterol fumarate
[(C19H24N2O4)2C4H4O4 : 804.882], calculated on the anhydrous basis.
Description Formoterol Fumarate Hydrate is a white
to yellowish white, crystalline powder.
Formoterol Fumarate Hydrate is freely soluble in glacial
acetic acid, soluble in methanol, very slightly soluble in
water or in ethanol and practically insoluble in ether.
A solution of Formoterol Fumarate in methanol (1 in
Meting pointAbout 138 C (with decomposition).
Identification (1) Dissolve 0.5 g of Formoterol Fumarate Hydrate in 20 mL of 0.5 mol/L sulfuric acid TS and
extract with three 25 mL volumes of ether. Wash the
combined ether extracts with 10 mL of 0.5 mol/L sulfuric
acid TS and evaporate the ether layer under reduced
pressure and dry the residue at 105 C for 3 hours: the residue melts at about 290 C (with decomposition, in a
sealed tube).
Formoterol Fumarate Hydrate and Formoterol Fumarate
Hydrate RS in methanol (1 in 40000) as directed under
(3) Determine the infrared spectrum of Formoterol
Fumarate and Formoterol Fumarate Hydrate RS as directed in the potassium bromide disk method under the
Purity (1) Heavy metalsProceed with 1.0 g of Formoterol Fumarate Hydrate according to Method 2 and
(2) Related substancesDissolve 0.20 g of Formoterol Fumarate Hydrate in 10 mL of methanol and use this
test solution, add methanol to make exactly 200 mL and
plate of silica gel for Thin-layer chromatography. Devel-

op the plate with a mixture of chloroform, dioxane, dehydrated ethanol and strong ammonia water (20 : 20 :
Allow the plate to stand for 5 minutes in iodine vapor:
solution.
Assay Weigh accurately about 0.7 g of Formoterol
Fumarate Hydrate, dissolve in 50 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 40.24 mg [(C19H24N2O4)2C4H4O4]
Fosfestrol
OPO3H2
CH3CH2
CH2CH3
H2O3PO
Diethylstilbestrol Diphosphate
C18H22O8P2: 428.31
Fosfestrol, when dried, contains not less than 98.5% and

not more than 101.0% of fosfestrol (C18H22O8P2).
Description Fosfestrol is a white, crystalline powder
and is odorless.
Fosfestrol is freely soluble in ethanol, soluble in formamide, slightly soluble in water and practically insoluble
in acetonitrile or in ether.
Fosfestrol dissolves in sodium hydroxide TS.
Meting pointAbout 234 C (with decomposition).
Identification (1) Dissolve 15 mg of Fosfestrol in 1
mL of sulfuric acid: a yellow to orange color is observed.
To this solution, add 10 mL of water: the color of the solution disappears.
(2) Place 0.4 g of Fosfestrol in a crucible, wet by
adding 0.1 mL of sulfuric acid and heat to carbonize.
Add 10 mL of water to the residue, stir well and filter.
Add 0.1 mL of nitric acid to the filtrate and heat in a water-bath for 15 minutes: this solution responds to the Qualitative Tests for phosphate.
(3) Determine the infrared spectrum of Fosfestrol and
Fosfestrol RS as directed in the potassium bromide disk

same wavenumbers.
pH Dissolve 0.10 g of Fosfestrol in 30 mL of water:
g of Fosfestrol in 15 mL of sodium hydroxide TS: the solution is clear and colorless.
(2) ChlorideDissolve 0.10 g of Fosfestrol in 30 mL
of ethanol, add 6 mL of dilute nitric acid and water to
test solution. Prepare the control solution as follows: to
0.70 mL of 0.01 mol/L hydrochloric acid VS, add 6 mL
of dilute nitric acid, 30 mL of ethanol and water to make
50 mL (not more than 0.248%).
(3) Heavy metalsProceed with 1.0 g of Fosfestrol
according to Method 4 and perform the test. Use a solution of magnesium nitrate in ethanol (1 in 5). Prepare the
(4) ArsenicWeigh about 1.0 g of Fosfestrol and
perform the test according to Method 3. Use a solution of
magnesium nitrate in ethanol (1 in 5) (not more than 2
ppm).
0.4 g of Fosfestrol, dissolve in a mixture of water and
formamide (1 : 1) to make exactly 200 mL and use this
0.112 g of monobasic potassium phosphate, previously
dried in a desicator (silica gel) to constant weight, dissolve in 10 mL of diluted sulfuric acid (1 in 10) and water to make exactly 1000 mL. Take exactly 10 mL of this
solution, add 100 mL of formamide and water to make
exactly 200 mL and use this solution as the standard solution. Take exactly 10 mL each of the test solution and
the standard solution and place in a volumetric flask, respectively. To each of these solutions, add 2.5 mL of
ammonium molybdate-sulfuric acid TS and 1 mL of 1amino-2-naphthol-4-sulfonic acid TS, shake, add water
to make 22 mL and allow to stand at 20 1 C for 30
minutes. Perform the test with these solutions, using a
solution obtained in the same manner with 10 mL of a
mixture of water and formamide (1 : 1) as the blank, as
Determine the absorbances, AT and AS, of the solutions
obtained from the test solution and the standard solution,
respectively, at 740 nm: the amount of free phosphoric
acid is not more than 0.2%.

1
AT
= A W 80.65
S
W: Amount (mg) of Fosfestrol.
(6) Related substancesDissolve 20 mg of Fosfe-
KP 9 443
strol in 100 mL of the mobile phase and use this solution
as the test solution. Pipet exactly 5 mL of this solution
and add the mobile phase to make exactly 50 mL. Pipet
exactly 3 mL of this solution, add the mobile phase to
Liquid Chromatography according to the following conditions. Determine each peak area of the test solution and
the standard solution by the automatic integration method: the total area of the peaks other than the principal
peak from the test solution is not larger than the peak
area of the principal peak from the standard solution.
about 25 C.
Mobile phase: A mixture of a solution of potassium
dihydrogen phosphate (1 in 500), acetonitrile and tetrabutyl-ammonium hydroxide TS (70 : 30 : 1).
time of fosfestrol is about 8 minutes.
System suitability
System performance: Dissolve 20 mg of Fosfestrol
and 8 mg of methyl p-hydroxy-benzoate in 100 mL of
the mobile phase. When the precedure is run with 10 L
condition, methyl p-hydroxybenzoate and fosfestrol are
eluted in this order with a resolution between their peaks
being not less than 3.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of fosfestrol obtained from 10
L of the standard solution is between 5 mm and 15 mm.
Time span of measurement: Three times as long as
the retention time of fosfestrol.
hours).
Assay Weigh accurately about 0.2 g of Fosfestrol, previously dried, dissolve in 60 mL of water and titrate with
0.1 mol/L sodium hydroxide VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). The end point
is the second equivalent point. Perform a blank determination and make any necessary correction.

= 10.708 mg of C18H22O8P2
Fosfestrol Tablets
Diethylstilbestrol Diphosphate Tablets
Fosfestrol Tablets contain not less than 93.0% and not
more than 107.0% of the labeled amount of fosfestrol
(C18H22O8P2: 428.31).
Method of Preparation Prepare as directed under the
Tablets, with Fosfestrol.
Identification (1) Take a portion of powdered Fosfestrol Tablets, equivalent to 0.5 g of fosfestrol according
to the labeled amount, add 50 mL of 0.1 mol/L hydrochloric acid TS, shake well and filter. To the filtrate, add
100 mL of ether, extract and evaporate carefully the ether
extract in a water-bath to dryness. Proceed with 15 mg of
the residue as directed in the Identification (1) under Fosfestrol.
(2) Dry 0.01 g of the residue obtained in (1) at 105 C
for 4 hours and determine the infrared absorption spectrum as directed in the potassium bromide disk method
under the Infrared Spectrophotometry: it exhibits absorption at the wavenumbers of about 2970 cm-1, 1605 cm-1,
1505 cm-1, 1207 cm-1 and 1006 cm-1.
Dissolution Perform the test with 1 tablet of Fosfestrol
Tablets at 50 revolutions per minute according to Method
2 under the Dissolution Test, using 900 mL of water.
Take 20 mL or more of the dissolved solution after 20
minutes from starting of the test and filter through a
Discard the first 10 mL of the filtrate, pipet exactly 2 mL
of the subsequent, add a solution of sodium hydroxide (1
in 250) to make exactly 20 mL and use this solution as
mg of Fosfestrol RS, previously dried at 105 C for 4
hours and dissolve in a solution of sodium hydroxide (1
in 250) to make exactly 100 mL. Pipet exactly 2 mL of
this solution, add a solution of sodium hydroxide (1 in
standard solution. Determine the absorbances, AT and AS,
The dissolution rate of Fosfestrol Tablets in 20 minutes is

not less than 80%.
AT
1
of fosfestrol (C18H22O8P2) = WS A C 180
S
WS: Amount (mg) of Fosfestrol RS
C: Labeled amount (mg) of fosfestrol (C18H22O8P2) in
1 tablet.

Uniformaity of Dosage Unit It meets the requirement.
Fosfestrol Tablets. Weigh accurately a portion of the
powder, equivalent to about 1 g of fosfestrol
(C18H22O8P2) according to the labeled amount, add 100
mL of a solution of sodium hydroxide (1 in 125), shake
well, add water to make exactly 500 mL and filter. Discard the first 30 mL of the filtrate, pipet exactly 2 mL of
the subsequent, add 30 mL of a solution of sodium hydroxide (1 in 125) and water to make exactly 250 mL
weigh accurately about 80 mg of Fosfestrol RS, previously dried at 105 C for 4 hours and dissolve in a solution of sodium hydroxide (1 in 125) to make exactly 50
mL. Pipet exactly 1 mL of this solution, add 10 mL of a
solution of sodium hydroxide (1 in 125) and water to
make exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of
the test solution and the standard solution, respectively,
Amount (mg) of fosfestrol (C18H22O8P2)

AT 25
= amount (mg) of Fosfestrol RS A 2
S
Fosfomycin Calcium Hydrate

H
H3C
PO3Ca
O
H2O
C3H5CaO4PH2O: 194.14
Fosfomycin Calcium Hydrate is the calcium salt of a
substance having antibacterial activity produced by the
growth of Streptomyces fradiae or by the chemical synthesis.
Fosfomycin Calcium Hydrate contains not less than 725
g (potency) per mg of fosfomycin (C3H7O4P: 138.06),
Description Fosfomycin Calcium Hydrate is a white
crystalline powder, and is tasteless.
Fosfomycin Calcium Hydrate is slightly soluble in water,
and practically insoluble in methanol, in acetone, in ethylacetate, in chloroform, or in ether.
Identification (1) Dissolve about 0.1 g of Fosfomycin
Calcium Hydrate in 3 mL of perchloric acid (1 in 4), add
1 mL of 0.1 mol/L sodium periodate TS, and heat for 30
minutes in 60 o C water bath. Allow to cool, add 50 mL
of water, neutralize with a saturated solution of sodium

hydrogen carbonate. To this solution add 1 mL of potassium iodide: a red color does not develop. Test with 3
mL of perchloric acid (1 in 4) in the same manner as the
above for a blank test solution: a red color develops.
(2) To 2 mL of an aqueous solution of Fosfomycin
Calcium Hydrate (1 in 500), add 1 mL of perchloric acid
and 2 mL of 0.1 mol/L sodium periodate TS, heat for 10
minutes in water bath, allow to cool, add 1 mL of ammonium molybdate sulfuric acid TS and 1 mL of 1-amino2-naphthol-4-sulfonic acid TS and allow to stand for 30
minutes: a blue color develops.
Calcium Hydrate (1 in 500), and add 1 mL of ammonium
oxalate TS: A white precipitate develops. Filter the precipitate, and add dilute acetic acid to the precipitate: the
precipitate is not dissolved. To this suspension add dilute
hydrochloric acid: the precipitate is dissolved.
(4) Fosfomycin Calcium Hydrate responds to the Qualitative Tests 1) for calcium salt.
D : -3 ~ -5 (0.5 g, 0.4
mol/L disodium dihydrogen ethylenediamine tetraacetate
TS, pH 8.5, 10 mL, 100 mm).
pH Weigh 40 mg of Fosfomycin Calcium Hydrate,
suspend in 10 mL of water, allow to cool to about 5 o C ,
and raise the temperature to room temperature. The pH
of the susepension is between 8.0 and 10.0.
Purity Heavy metalsProceed with 1.0 g of Fosfomycin Calcium Hydrate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL of
Water Not more than 12.0 % (0.1 g, volumetric titration, direct titration). Use a mixture of formamide for
water determination and methanol for water determination (2 : 1) instead of methanol for water determination
Phosphorus Content Weigh accurately about 0.1 g of
Fosfomycin Calcium Hydrate, transfer into 100 mL Erlenmeyer flask, add 40 mL of 0.05 mol/L sodium periodate TS and 2 mL of pechloric acid, heat for 1 hour in
water bath and allow to cool, and add water to make exactly 200 mL. Pipet exactly 10 mL of this solution and
transfer into 100 mL volumetric flask, and add 1 mL of
potassium iodide TS: the color of the solution is brown.
To this solution add sodium thiosulfate TS until the solution is colorless, add water to make exactly 100 mL, and
accurately 70 mg of potassium dihydrogenphosphate,
proceed with this solution in the same manner as directed
for the preparation of the test solution, and use the solution so obtained as the standard solution. Proceed and
prepare a solution in the same manner for the preparation
of the test solution without using Fosfomycin Sodium,
and use the solution so obtained as the blank solution.
KP 9 445
Pipet 5 mL of each of the test solution, the standard solution, and the blank solution, transfer each into a 25 mL
volumetric flask, add 2.5 mL of ammonium molybdatesulfuric acid TS and 1 mL of 1-amino-2-naphthol-4sulfonic acid TS, mix with shaking, and add water to
make exactly 25 mL. After allowing these solutions to
stand for 30 minutes at 20 1 o C , perform the test with
these solutions as directed under Ultraviolet-visible
Spectrophotometry, using water as a blank, and determine the absorbances at 740 nm, A1, A2, and A3, of the
test solution, the standard solution and the blank solution
(not less than 15.2 % and not more than 16.7 %).
lution. Keep the standard stock solution below 5 o C , and

use within 7 days. Take exactly a suitable amount of the
standard stock solution before use, add 0.05 mol/L Tris

tight containers.
Amount [%] of phosphorus

=
A1 A3
W2
22 .76
A2 A3
W1
A1: Absorbance of the test solution

A2: Absorbance of the standard solution
A3: Absorbance of the blank solution
W1: Amount (mg) of Fosfomycin Sodium
W2: Amount (mg) of potassium dihydrogenphosphate
22.76: Content (%) of phosphorus in potassium dihydrogenphosphate
Calcium Content Weigh accurately about 0.2 g of
Fosfomycin Calcium Hydrate, transfer into a 250 mL
flask, add 4 mL of 1 mol/L hydrochloric acid TS, and
shake well until the sample is completely dissolved. To
this solution add 100 mL of water, 9 mL of sodium hydroxide TS and 0.1 g of methylthymol bluesodium chloride indicator, and titrate with 0.05 mol/L disodium dihydrogen ethylenediamine tetraacetate VS until the color
of the solution changes from clear to gray or gray-purple
(not less than 19.6 % and not more than 21.7 %).
Each mL of 0.05 mol/L disodium dihydrogen ethylenediamine tetraacetate VS = 2.004 mg of Ca

Assay The Cylinder-plate method (1) Agar media for
seed and base layer- Use the media (1) under the Assay
in Fosfomycin Sodium.
(2) Test organism- Proteus sp. MB 838.
(3) Test organism suspension- Prepare according to
(3) under the Assay in Fosfomycin Sodium.
(4) Weigh accurately about 50 mg (potency) of Fosfomycin Calcium Hydrate, and dissolve in 0.05 mol/L
Tris buffer solution, pH 7.0 to make the solution so that
each mL contains 1 mg (potency). Take exactly a suitable
amount of this solution, add 0.05 mol/L Tris buffer solution, pH 7.0 to make solutions so that each mL contains
10.0 g (potency) and 5.0 g (potency), and use these
solutions as the high concentration test solution and the
low concentration test solution, respectively. Separately,
weigh accurately about 10 mg (potency) of Fosfomycin
RS, and dissolve in 0.05 mol/L Tris buffer solution, pH
7.0 to make the solution so that each mL contains 500 g
(potency), and use the solution as the standard stock so-
Fosfomycin Sodium
H
H3C
PO3Na2
O
C3H5Na2O4P: 182.02
Fosfomycin Sodium is the sodium salt of a substance
having antibacterial activity produced by the growth of
Streptomyces fradiae or by the chemical synthesis.
Fosfomycin Sodium contains not less than 700 g (potency) per mg of fosfomycin (C3H7O4P: 138.06), calculated on the anhydrous basis.
Description Fosfomycin Sodium is a white crystalline
powder, and has a little bit of salty taste.
Fosfomycin Sodium is very soluble in water, sparingly
soluble in methanol, and practically insoluble in ethanol
or in ether.
Identification (1) Dissolve about 0.1 g of Fosfomycin
Sodium in 3 mL of perchloric acid (1 in 4), add 1 mL of
0.1 mol/L sodium periodate TS, and heat for 30 minutes
in 60 C water bath. Allow to cool, add 50 mL of water,
neutralize with sodium hydrogen carbonate solution, and
add 1 mL of potassium iodide: a red color does not develop. Test with 3 mL of perchloric acid (1 in 4) in the
same manner as the above for a blank test solution: a red
color develops.
Sodium (1 in 250), add 1 mL of perchloric acid and 2 mL
of 0.1 mol/L sodium periodate TS, heat for 10 minutes in
water bath, allow to cool, add 1 mL of ammonium molybdate sulfuric acid TS and 1 mL of 1-amino-2naphthol-4-sulfonic acid TS and allow to stand for 30
minutes: a blue color develops.
(3) Fosfomycin Sodium responds to the Qualitative
[ ] 20
D : -3.5 ~ -5.5 (0.5 g,

of Fosfomycin Sodium in 1 mL of water is between 8.5
and 10.5.
Purity Heavy metalsWeigh 2.0 g of Fosfomycin Sodium, dissolve in 4 mL of acetic acid and water to make
50 mL, and use this solution as the test solution. Perform
the test with this solution. Prepare the control solution
with a mixture of 2.0 mL of standard lead solution, 2 mL
of dilute acetic acid and 46 mL of water (not more than
10 ppm).
Sterility Test It meets the requirement, when Fosfomycin Sodium is used in a sterile preparation.
fosfomycin, when Fosfomycin Sodium is used in a sterile
preparation.
direct titration).
Phosphorus Content Weigh accurately about 0.1 g of
Fosfomycin Sodium, transfer into 100 mL Erlenmeyer
flask, add 40 mL of 0.05 mol/L sodium periodate TS and
2 mL of pechloric acid, heat for 1 hour in water bath and
allow to cool, and add water to make exactly 200 mL.
Pipet exactly 10 mL of this solution and transfer into 100
mL volumetric flask, and add 1 mL of potassium iodide
TS: the color of the solution is brown. To this solution
add sodium thiosulfate TS until the solution is colorless,
add water to make exactly 100 mL, and use this solution
as the test solution. Separately, weigh accurately 70 mg
of potassium dihydrogenphosphate, proceed with this solution in the same manner as directed for the preparation
of the test solution, and use the solution so obtained as
the standard solution. Proceed and prepare a solution in
the same manner for the preparation of the test solution
without using Fosfomycin Sodium, and use the solution
so obtained as the blank solution. Pipet 5 mL of each of
the test solution, the standard solution, and the blank solution, transfer each into a 25 mL volumetric flask, add
2.5 mL of ammonium molybdatesulfuric acid TS and 1
mL of 1-amino-2-naphthol-4-sulfonic acid TS, mix with
shaking, and add water to make exactly 25 mL. After allowing these solutions to stand for 30 minutes at 20 1
C , perform the test with these solutions as directed under Ultraviolet-visible Spectrophotometry, using water as
a blank, and determine the absorbances at 740 nm, A1, A2,
and A3, of the test solution, the standard solution and the
blank solution (not less than 16.2 % and not more than
17.9 %).
Amount [%] of phosphorus

=
A1 A3
W2
22 .76
A2 A3
W1
A1: Absorbance of the test solution

A2: Absorbance of the standard solution
A3: Absorbance of the blank solution
W1: Amount (mg) of Fosfomycin Sodium
W2: Amount (mg) of potassium dihydrogenphosphate
22.76: Content (%) of phosphorus in potassium dihydrogenphosphate
5.0 g
Yeast extract
2.0 g
Meat extract
3.0 g
Agar
15.0 ~ 20.0 g
Water
1000 mL
of the solution so that it will be between 6.5 and 6.6 after
sterilization.
(2) Test organism- Proteus sp. MB 838.
(3) Test organism suspension- Incubate the test organism on the slant of the agar medium for transferring
test organism at 37 C for 40 ~ 48 hours. Sub-culture at
least three times. Inoculate the grown organisms onto the
surface of 300 mL of the agar medium for transferring
test organism in a Roux bottle, incubate at 37 C for 40 ~
48 hours, and suspend the grown organisms in about 30
mL of water. To the suspension add water to dilute 10fold so that the percent transmission at 560 nm of the
suspension is 17 %. Keep the suspension of test organism at 10 C or below and use within 7 days. Add 1.0 ~ 2
mL of the suspension of test organism to 100 mL of the
agar medium for seed layer previously kept at 48 C, mix
with shaking, and use this as the seeded agar layer.
(4) Weigh accurately about 50 mg (potency) of Fosfomycin Sodium, and dissolve in 0.05 mol/L Tris buffer
solution, pH 7.0 to make the solution so that each mL
contains 1 mg (potency). Take exactly a suitable amount
of this solution, add 0.05 mol/L Tris buffer solution, pH
7.0 to make solutions so that each mL contains 10.0 g
(potency) and 5.0 g (potency), and use these solutions
as the high concentration test solution and the low concentration test solution, respectively. Separately, weigh
accurately about 10 mg (potency) of Fosfomycin RS, and
dissolve in 0.05 mol/L Tris buffer solution, pH 7.0 to
make the solution so that each mL contains 500 g (potency), and use the solution as the standard stock solution.
Keep the standard stock solution below 5 o C , and use
standard stock solution, add 0.05 mol/L Tris buffer solution, pH 7.0 to make solutions so that each mL contains
10.0 g (potency) and 5.0 g (potency), and use these
solutions as the high concentration standard solution and
the low concentration standard solution, respectively.
Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under Microbial Assay for Antibiotics.
KP 9 447
Fructose
O OH
HO
CH2OH
HO
OH
C6H12O6: 180.16
Fructose, when dried, contains not less than 98.0% and
not more than 101.0% of fructose (C6H12O6).
Description Fructose is a colorless to white crystal or
crystalline powder, is odorless and has a sweet taste.
Fructose is very soluble in water, sparingly soluble in
Fructose is hygroscopic.
Identification (1) Add 2 to 3 drops of a solution of
Fructose (1 in 20) to 5 mL of boiling Fehlings TS: a red
(2) Determine the infrared spectrum of Fructose and
Fructose RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
pH Dissolve 4.0 g of Fructose in 20 mL of water: the
pH of the solution is between 4.0 and 6.5.
25.0 g of Fructose in 50 mL of water: the solution is
solution.
Control solutionTo a mixture of 1 mL of cobaltous

chloride stock CS, 3 mL of ferric chloride stock CS and 2
mL of cupric sulfate stock CS and add water to make 10
mL. To 3 mL of the solution, add water to make 50 mL.
(2) AcidDissolve 5 g of Fructose in 50 mL of
freshly boiled and cooled water and add 3 drops of phenolphthalein TS and 0.6 mL of 0.01 mol/L sodium hydroxide VS: a red color is observed.
(3) ChloridePerform the test with 2.0 g of Fructose.
hydrochloric acid VS (not more than 0.018%).
(4) SulfatePerform the test with 2.0 g of Fructose.
(5) SulfiteDissolve 0.5 g of Fructose in 5 mL of
water and add 0.25 mL of 0.01 mol/L iodine: the color of
the solution is yellow.
(6) Heavy metalsProceed with 5.0 g of Fructose

(7) CalciumDissolve 0.5 g of Fructose in 5 mL of
water, add 2 to 3 drops of ammonia TS and 1 mL of ammonium oxalate TS and allow to stand for 1 minute: the
solution is clear.
(8) ArsenicDissolve 1.5 g of Fructose in 5 mL of
water, heat with 5 mL of dilute sulfuric acid and 1 mL of
bromine TS on a water-bath for 5 minutes, concentrate to
5 mL and cool. Perform the test with this solution as the
test solution (not more than 1.3 ppm).
(9) 5-HydroxymethylfurfuralsDissolve 5.0 g of
Fructose in 100 mL of water and read the absorbance at
284 nm as directed under the Ultraviolet-visible Spectrophotometry: the absorbance is not more than 0.32.
Assay Weigh accurately about 4 g of Fructose, previously dried, dissolve in 0.2 mL of ammonia TS and 80
mL of water and after standing for 30 minutes, add water
to make exactly 100 mL and determine the optical rotation, D , in a 100 mm cell at 20 1 C as directed under the Optical Rotation Determination.
Amount (mg) of fructose (C6H12O6) = | D | 1087.0

Fructose Injection
Fructose Injection is an aqueous solution for injection.
Fructose Injection contains not less than 95.0% and not
more than 105.0% of the labeled amount of fructose
(C6H12O6: 180.16).
Method of Preparation Prepare as directed under Injections, with Fructose. No preservative is added.
Description Fructose is a colorless to white crystal or
crystalline powder, is odorless and has a sweet taste.
Identification (1) Take a volume of Fructose Injection,
equivalent to 1 g of Fructose according to the labeled
amount, dilute with water or concentrate on a water-bath
to make 20 mL, if necessary and use this solution as the
test solution. Add 2 to 3 drops of the test solution to 5
mL of boiling Fehlings TS: a red precipitate is produced.
(2) Take 10 mL of the test solution obtained in (1),
add 0.1 g of resorcin and 1 mL of hydrochloric acid and
warm on a water-bath for 3 minutes: a red color is observed.
pH
COOH
Purity (1) Heavy metalsTake a volume of Fructose

Injection, equivalent to 5.0 g of Fructose, according to
Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution.
(2) ArsenicTake a volume of Fructose Injection,
equivalent to 1.5 g of Fructose according to the labeled
amount, dilute with water or concentrate on a water-bath
to make 5 mL, if necessary and add 5 mL of dilute sulfuric acid and 1 mL of bromine TS. Proceed as directed
in the Purity (8) under Fructose.
Residue on Ignition Measure exactly a volume of
Fructose Injection, equivalent to about 2.0 g of Fructose
according to the labeled amount, evaporate on a waterbath to dryness and perform the test: the residue weighs
not more than 2.0 mg.
Pyrogen Test Perform the test with Fructose Injection
stored in a container in a volume exceeding 10 mL: it
meets the requirement of the Pyrogen Test. When the
Fructose concentration is greater than 10 w/v%, dilute
with the Fructose solution with water for injection to
make 10 w/v% and perform the test.
It

Assay Measure exactly a volume of Fructose Injection,
equivalent to about 4 g of fructose (C6H12O6: 180.16),
add 0.2 mL of ammonia TS, dilute with water to make
exactly 100 mL, shake well and after allowing to stand
for 30 minutes, determine the optical rotation, D , in a
100 mm cell at 20 1 C as directed under the Optical
Rotation Determination.
Amount (mg) of fructose (C6H12O6) = | D | 1087.0

used.
Furosemide
NHCH2
H2NO2S
Cl
C12H11ClN2O5S: 330.74
Furosemide, when dried, contains not less than 98.0%
and not more than 101.0% of furosemide
(C12H11ClN2O5S).
Description Furosemide is a white crystal or crystalline powder.
Furosemide is freely soluble in dimethylformamide, soluble in methanol, sparingly soluble in ethanol, slightly
soluble in glacial acetic acid and practically insoluble in
water.
Furosemide dissolves in sodium hydroxide TS.
Furosemide is gradually colored by light.
Identification (1) Dissolve 25 mg of Furosemide in 10
mL of methanol. To 1 mL of this solution, add 10 mL of
2 mol/L hydrochloric acid TS. Heat the solution in a water-bath under a reflux condenser for 15 minutes, cool
and add 18 mL of sodium hydroxide TS to make weakly
acidic: this solution responds to the Qualitative Tests for
primary aromatic amines. A red to red-purple color is observed.
Furosemide and Furosemide RS in dilute sodium hydroxide TS (1 in 25,000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(3) Determine the infrared spectrum of Furosemide
and Furosemide RS as directed in the potassium bromide
same wavenumbers.
g of Furosemide in 10 mL of a solution of sodium hydroxide (1 in 50): the solution is colorless and clear.
(2) ChlorideDissolve 2.6 g of Furosemide in 90
mL of dilute sodium hydroxide TS, add 2 mL of nitric
acid and filter. To 25 mL of the filtrate, add 6 mL of dilute nitric acid and water to make 50 mL and perform the
control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS, 6 mL of dilute nitric acid and water to make
(3) SulfateTo 20 mL of the filtrate in (2), add 1 mL
of dilute hydrochloric acid and perform the test using this
hydrochloric acid and water to make 50 mL (not more
than 0.030%).
KP 9 449
(4) Heavy metalsProceed with 2.0 g of Furosemide
(5) Related substances Dissolve 25 mg of Furosemide in 25 ml. of the dissolving solution, and use this
test solution, add the dissolving solution to make exactly
Perform the test with exactly 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and determine each peak area by the automatic integration method: the area of each peak appeared ahead
of the peak of furosemide is not more than 2/5 times the
peak area of furosemide from the standard solution, the
area of each peak appeared behind the peak of furosemide is not more than 1/4 times the peak area of furosemide from the standard solution, and the total area of
these peaks is not more than 2 times the peak area of furosemide from the standard solution.
Dissolving solutionTo 22 mL of anhydrous acetic
acid, add a mixture of water and acetonitrile (1 : 1) to
make l000 mL.
about 25 C.
Mobile phase: A mixture of water, tetrahydrofuran
and glacial acetic acid (70 : 30 : 1).
time of furosemide is about 18 minutes.
System suitability
mL of the standard solution, and add the dissolving solution to make exactly 50 mL: the peak area of furosemide
obtained from 20 L of this solution is equivalent to 3.2
to 4.8% of that obtained from 20 L of the standard solution.
the symmetrry factor of the peak of furosemide are not
above operating conditions, the relative standard deviation of the peak area of furosemide is not more than
2.0%.
Time span of measurement: About 2.5 times as long as
the retention rime of furosemide beginning after the solvent peak.

hours).
Assay Weigh accurately about 0.5 g of Furosemide,
previously dried, dissolve in 50 mL of dimethylformamide and titrate with 0.1 mol/L sodium hydroxide VS
until the color of the solution changes from yellow to
blue (indicator: 3 drops of bromothymol blue TS). Perform a blank determination with a mixture of 50 mL of
dimethylformamide and 15 mL of water and make any

= 33.074 mg of C12H11ClN2O5S
tight containers.
Furosemide Tablets
Furosemide Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of furosemide
(C12H11ClN2O5S: 330.74).
Method of Preperation Prepare as directed under Tablets, with Furosemide.
Identification (1) Shake well a quantity of powdered
Furosemide Tablets, equivalent to 0.2 g of furosemide
according to the labeled amount, with 40 mL of acetone,
and filter. To 0.5 mL of the filtrate add 10 ml of 2 mol/L
hydrochloric acid TS and heat under a reflux condenser
on a water bath for 15 minutes. After cooling, add 18 mL
of sodium hydroxide TS to make the solution slightly
acidic: the solution responds to the Qualitative Tests for
Primary Aromatic Amines, producing a red to red-purple
color.
(2) Determine the absorption spectrum of the test solution obtained in the Assay as directed under Ultravioletvisible Spectrophotometry : it exhibits maxima between
227 nm and 231 nm, between 269 nm and 273 nn, and
Purity To a quantiy of powdered Furosemide Tablets,
equivalent to 40 mg of furosemide according to the labeled amount, add about 30 mL of acetone, shake well,
and add acetone to make exactly 50 mL. Centrifuge the
solution, add 3.0 mL of water to 1.0 mL of the supenlatant liquid, cool in ice, add 3.0 mL of dilute hydrochloric
acid and 0.15 mL of sodium nitrite TS, shake, and allow
to stand for 1 minute. Add 1.0 ml. of ammonium amidosulfate TS, shake well, allow to stand for 3 minutes, add
1.0 mL of N,N-diethyl-N-1-naphthylethylenediamine
oxalate TS, shake well, and allow to stand for 5 minutes.

Perform the test with this solution as directed under Ultraviolet-visible Spcctrophotometry, using a solution
prepared in the same manner with 1.0 mL of acetone as
the blank: the absorbance at 530 nm is not more than
0.10.
Dissolution Test Perform the test with 1 tablet of Furosemide Tablets at 50 revolutions per minute according to
the Method 2, using 900 mL of 2nd fluid for dissolution
test as the dissolution medium. Withdraw 20 mL or more
of the dissolution medium 15 minutes after starting the
test for a 20-mg tablet or 30 minutes after for a 40-mg
tablet, and filter through a membrane filter with pore size
of not more than 0.45 m. Discard the first 10 mL of the
filtrate, pipet V mL of the subsequent filtrate, add 2nd
fluid for dissolution test to make exactly V mL so that
each mL contains about l0 g of furosemide
(C12H11ClN2OS) according to the labeled amount, and
accurately about 20 mg of Furosemide RS, previously
dried at 105 C for 4 hours, and dissolve in 5 mL of methanol, and add 2nd fluid for dissolution test to make exactly 100 mL. Pipet 5 mL of this solution, add 2nd fluid
for dissolution test to make exactly 100 mL, and use this
solution as the standard solution. Determine the absorbances, AT and AS of the test solution and the standard
solution at 277 nm as directed under Ultraviolet-visible
Spectrophotometry.
The dissolution rate of Furosemide Tablets in 60 minutes

tion of the powder, equivalent to about 40 mg of furoscmide (C12H11ClN2O5S), add about 70 mL of 0.05 mol/L
sodium hydroxide TS, shake well, and add 0.05 mol/L
sodium hydroxide TS to make exactly 100 mL. Filter,
discard the first 10 mL of the filtrate, pipet exactly 2 mL
of the subsequent filtrate, add 0.05 mol/L sodium hydroxide TS to make exactly 100 mL, and use this solution as the test solution. Separately, weigh accurately
about 20 mg of Furosemide RS, previously dried at
105 C for 4 hours, and dissolve in 0.05 mol/L sodium
hydroxide TS to make exactly 50 mL. Pipet exactly 2 mL
of this solution, add 0.05 mol/l. sodium hydroxide TS to
make exactly 100 mL, and use this solution as the standard solution. Determine the absorbances, AT and AS, of
the test solution and the standard solution at 271 nm as
Amount (mg) of furosemide (C12H11ClN2O5S)
AT
= amount (mg) of Furosemide RS A
S
Packaging and Storage Preserve well-closed containers.
Fursultiamine Hydrochloride
H3C
NH2
CHO
N
CH2N
HCl
SCH2
O

of furosemide (C12H11ClN2O5S) = amount (mg) of Furosemide RS AT V 1 45
AS
C : Labeled amount
(C12H11ClN2O5S) in 1 tablet
of
furosemide
Uniformity of Dosage Units Perform the test according to the following method: it meets the requirement.
To 1 tablet of Furosemide Tablets add a suitable amount
of 0.05 mol/L sodium hydroxide TS, shake to disintegrate, then add 0.05 mol/L sodium hydroxide TS to make
exactly V mL, so that each mL contains about 0.4 mg of
furosemide (C12H11ClN2O5S). Filter the solution, discard
the first 10 mL of the filtrate, pipet the subsequent 2 mL
of the filtrate, add 0.05 mol/L sodium hydroxide TS to
solution. Proceed as directed in the Assay.
Amount (mg) of furosemide (C12H11ClN2O5S) = amount

(mg) of Furosemide RS AT V
AS
CH2CH2OH
and enantiomer
C17H26N4O3S2HCl: 435.00
(mg)
H3C
50
Assay Weigh accurately the mass of not less than 20

Furosemide Tablets, and powder. Weigh accurately a por-
Fursultiamine Hydrochloride contains not less than

98.5% and not more than 101.0% of fursultiamine hydrochloride (C17H26N4O3S2HCl), calculated on the anhydroys basis.
Description Fursultiamine Hydrochloride is a white
crystal or crystalline powder, is odorless or has a characteristic odor and has a bitter taste.
Fursultiamine Hydrochloride is freely soluble in water, in
methanol or in ethanol and practically insoluble in ether.
Identification (1) Dissolve 5 mg of Fursultiamine Hydrochloride in 6 mL of 0.1 mol/L hydrochloric acid TS,
add 0.1 g of zinc dust, allow to stand for several minutes
and filter. To 3 mL of the filtrate, add 3 mL of sodium
hydroxide TS and 0.5 mL of potassium ferricyanide TS,
then add 5 mL of isobutanol, shake vigorously for 2 minutes, allow to stand to separate the isobutanol layer and
examine under ultraviolet light (main wavelength: 365
nm): the isobutanol layer shows a blue-purple fluorescence. The fluorescence disappears by acidifying and appears again by alkalifying.
KP 9 451
(2) Determine the infrared absorption spectra of Fursultiamine Hydrochloride and Fursultiamine Hydrochloride RS, previously dried in a desiccator (in vacuum,
P2O5) for 24 hours, as directed in the potassium bromide
same wavenumbers. If any differences appear, dissolve
the Fursultiamine Hydrochloride in water, evaporate the
water and dry the residue in a desiccator (in vacuum,
P2O5) for 24 hours and repeat the test.
(3) A solution of Fursultiamine Hydrochloride (1 in
g of Fursultiamine Hydrochloride in 20 mL of water: the
(2) SulfatePerform the test with 1.5 g of Fursultiamine Hydrochloride. Prepare the control solution with
0.35 mL of 0.005 mol/L sulfuric acid VS: not more than
0.011%.
(3) Heavy metalsProceed with 1.0 g of Fursultiamine Hydrochloride according to Method 2 and perform
(4) Related substancesDissolve 0.10 g of Fursultiamine Hydrochloride in 100 mL of the mobile phase
and use this solution as the test solution. Pipet exactly 1
mL of the test solution, add the mobile phase to make
exactly 100 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography. Determine peak area of each solution by the automatic integration method: the total area
of the peaks other than the peak of fursultiamine from
the test solution is not larger than the peak area of fursultiamine from the standard solution.
the operating conditions under the Assay.
Detector sensitivity: Adjust the detection sensitivity
so that the peak height of fursultiamine from 10 L of
the retention time of fursultiamine.
Assay Weigh accurately about 55 mg each of Fursultiamine Hydrochloride and Fursultiamine Hydrochloride
RS, separately determined for water, dissolve each in 50
mL of water, add exactly 10 mL each of the internal
standard solution and then add water to make exactly 100
mL. Take 8 mL each of the solutions, add water to make

the following conditions and calculate the ratios, QT and
QS, of the peak area of fursultiamine to that of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of fursultiamine hydrochloride
(C17H26N4O3S2HCl) = amount (mg) of
Fursultiamine Hydrochloride RS, calculated
QT
on the anhydrous basis Q
S
Internal standard solutionA solution of isopropyl
p-aminobenzoate in ethanol (3 in 400)
about 50 C.
sulfonate in 1000 mL of diluted glacial acetic acid (1 in
100). Take 675 mL of this solution, add 325 mL of a
mixture of methanol and acetonitrile (3 : 2).
time of fursultiamine is about 9 minutes.
Selection of the column: Proceed with 10 L of the
standard solution under the above operating conditions
and calculate the resolution. Use a column giving elution
of fursultiamine and the internal standard in this order
than 10.
Gabexate Mesilate
NH
H 2N
O
NH(CH 2)5
O
O
OCH 2CH 3
CH 3SO 3H
C16H23N3O4CH4O3S: 417.48
Gabexate Mesilate, when dried, contains not less than
98.5% and not more than 101.0% of gabexate mesilate
(C16H23N3O4CH4O3S).
Description Gabexate Mesilate is a white crystal or
crystalline powder.
Gabexate Mesilate is very soluble in water, freely soluble

Identification (1) Take 4 mL of a solution of Gabexate
Mesilate (1 in 2000), add 2 mL of -naphthol TS and 1
mL of diacetyl TS and allow to stand for 10 minutes: a
(2) Dissolve 1 g of Gabexate Mesilate in 5 mL of water, add 2 mL of sodium hydroxide TS and heat on a water-bath for 5 minutes. After cooling, add 2 mL of dilute
nitric acid and 5 mL of ethanol, shake, add 5 drops of
ferric chloride TS and shake: a purple color is observed.
Gabexate Mesilate and Gabexate Mesilate RS (1 in
(4) Take 0.1 g of Gabexate Mesilate, add 0.2 g of sodium hydroxide, fuse by heating gently and continue the
heating for 20 to 30 seconds. After cooling, add 0.5 mL
of water and 3 mL of dilute hydrochloric acid and warm:
the gas evolved changes a potassium iodate-starch paper
to blue.
pH Dissolve 1.0 g of Gabexate Mesilate in 10 mL of
g of Gabexate Mesilate in 10 mL of water: the solution is
(2) Heavy metalsProceed with 2.0 g of Gabexate
Mesilate according to Method 1 and perform the test.
(3) ArsenicDissolve 2.0 g of Gabexate Mesilate in
20 mL of 1 mol/L hydrochloric acid by heating on a water-bath and continue the heating for 20 minutes. After
cooling, centrifuge and use 10 mL of the supernatant liquid as the test solution. Perform the test (not more than 2
ppm).
(4) Ethyl parahydroxybenzoateWeigh 50 mg of
Gabexate Mesilate, previously dried and dissolve in dilute ethanol to make exactly 100 mL. Pipet 5.0 mL of
solution and use this solution as the test solution. Separately, dissolve 5.0 mg of ethyl parahydroxybenzoate in
dilute ethanol to make exactly 100 mL. Pipet 1.0 mL of
this solution and add dilute ethanol to make exactly 20
mL. Take exactly 5 mL of this solution, add exactly 5 mL
of the internal standard solution and use this solution as
the test solution and the standard solution as directed under the Liquid Chromatography according to the operating conditions in the Assay and calculate the ratios, QT
and QS , of the peak area of ethyl parahydroxybenzoate
to that of the internal standard, respectively: QT is not
larger than QS .
Internal standard solutionA solution of butyl para-
hydroxybenzoate in diluted ethanol (1 in 5000).

(5) Related substancesDissolve 0.20 g of Gabexate Mesilate in 5 mL of ethanol and use this solution as
the test solution. Pipet 1.0 mL of the test solution, add
of ethyl acetate, water and glacial acetic acid (3 : 1 : 1) to
a distance of about 10 cm and air-dry the plate until it has
no acetic odor. Spray evenly a solution of 8-oxyquinoline
in acetone (1 in 1000) on the plate and after air-drying,
spray evenly bromine-sodium hydroxide TS: the spots
Assay Weigh accurately about 50 mg of Gabexate Mesilate and Gabexate Mesilate RS, previously dried and
dissolve each in dilute ethanol to make exactly 100 mL.
Pipet 5.0 mL each of these solutions, add exactly 5 mL
each of the internal standard solution and use these solutions as the test solution and the standard solution, respectively. Perform the test with 3 L each of the test solution and the standard solution as directed under the
Thin-layer chromatography according to the following
peak area of gabexate to that of the internal standard, for
Amount (mg) of gabexate mesilate

(C16H23N3O4.CH4O3S) = amount (mg) of Gabexate Mesilate RS
QT
QS
Internal standard solutionA solution of butyl parahydroxybenzoate in diluted ethanol (1 in 5000).

about 25 o C .
Mobile phase: A mixture of methanol, a solution of
sodium lauryl sulfate (1 in 1000), a solution of sodium 1heptane sulfonate (1 in 200) and glacial acetic acid (540 :
200 : 20 : 1).
KP 9 453
time of Gabexate is about 13 minutes.
System suitability
with 3 L of the standard solution, as directed under
the above operating condition, the internal standard and
Gabexate are eluted in this order with the resolution between their peaks being not less than 5.
deviation of the ratios of the peak area of Gabexate to
that of the internal standard is not more than 1.0%
Gallamine Triethiodide
CH3
CH3
Gallamine Triethiodide (1 in 100) is colorless and clear.

(2) Heavy metalsProceed with 1.0 g of Gallamine
Triethiodide according to Method 1, and perform the test.
hours).
Assay Weigh accurately 25 mg each of Gallamine Triethiodide and Gallamine Triethiodide RS, dissolve in the
mobile phase to make exactly 25 mL each and use these
respectively. Perform the test with 10 L each of the test
Liquid Chromatography according to the following operating conditions and determine the area of the peak of
gallamine triethiodide in the test solution, AT , and in
the standard solution, AS , respectively.
N
O
Amount (mg) of gallamine triethiodide (C30H60I3N3O3)
CH3
= 25 C
CH3
O
N
CH3
C: Concentration (mg/mL) of gallamine triethiodide

in the standard solution.
CH3
O
N
CH3
CH3
AT
AS
CH3
C30H60I3N3O3 : 891.53
Gallamine Triethiodide contains not less than 98% and
not more than 101.0% of gallamine triethiodide
(C30H60I3N3O3), calculated on the dried basis.
Description
Gallamine Triethiodide is a white,
amorphous power and is odorless.
Gallamine Triethiodide is very soluble in water, sparingly soluble in ethanol and very slightly soluble in chloroform.
Gallamine Triethiodide is hygroscopic.
Gallamine Triethiodide and Gallamine Triethiodide RS
(2) A solution of Gallamine Triethiodide (1 in 100)
responds to the Qualitative Tests for iodide.
pH Dissolve 1 g of Gallamine Triethiodide in 50 mL of
Purity (1) Clarity and color of solutionA solution of
(3-10 m in particle diameter).
Mobile phase: A mixture of sodium perchlorate buffer and acetonitrile (69:31).
System suitability
with 10 L of the standard solution under the above operating conditions, the number of theoretical plates is not
less than 5000 with the symmetry factor being not more
than 1.4.
above operating conditions, the relative standard deviation of the areas of the peak of gallamine triethiodide is
not more than 2.0%.
Sodium perchlorate bufferDissolve sodium perchlorate in water to render the concentration of 0.14
mol/L and adjust the pH to 3.0 by addition of 10 mol/L
sodium hydroxide TS or of 0.05 mol phosphoric acid.
tight containers.
67
Gallium Citrate ( Ga) Injection

Gallium (67Ga) Citrate Injection is an aqueous solution
for injection containing Gallium (67Ga) Citrate Injection.
It conforms to the requirements of Gallium (67Ga) Citrate
Injection specified in the Korean Pharmaceutical Codex(Third Edition, 2007).
The Insoluble Particulate Matter Test for Injections is not
applied to this injection.
graphy. Spot 50 L of the test solution and the standard

solution on a plate of silica gel for thin-layer chromatography. Develop the plate with the developing solvent
which is a mixture of chloroform, ammonia solution (28)
and methanol (2:1:1), and air-dry the plate. Then allow
the plate to stand in iodine chamber containing 2 ~ 4 g of
iodine for 3 ~ 5 minutes. The spots obtained from the test
solution are the same with the corresponding spots from
the standard solution in color tone and the Rf value, respectively.
Description Gallium (67Ga) Citrate Injection is a clear,

colorless or light red liquid.

+107 ~ +121
D :
(0.25 g calculated on the dried basis, water, 25 mL, 200
mm)
Gentamicin Sulfate

of Gentamicin Sulfate in 10 mL of water is between 3.5
and 5.5.
R1
HN
Sterility Test It meets the requirement, when Gentamicin Sulfate is used in a sterile preparation.
R3
R2

gentamicin, when Gentamicin Sulfate is used in a sterile
preparation.
O
NH2
NH2
OH
HN
O
CH3
HO
xH2SO4
Loss on Drying Not more than 18.0 % (0.151 g, reduced pressure not exceeding 0.67 kPa, 110 C, 3 hours).
CH3
OH
Gentamicin C1: R1 = CH3

Gentamicin C1a: R1 = H
Gentamicin C2: R1 = H
Gentamicin C2a: R1 = H
Gentamicin C2b: R1 = CH3
NH2
R2 = CH3
R2 = H
R2 = CH3
R2 = H
R2 = H
R3 = H
R3 = H
R3 = H
R3 = CH3
R3 = H
Gentamicin Sulfate is the sulfate of a mixture of aminoglycoside substances having antibacterial activity produced by the growth of Micromonospora purpurea or
Micromonospora echinospora.
Gentamicin Sulfate contains not less than 590 g (potency) per mg of gentamicin C1 (C21H43N5O7: 477.60), calculated on the dried basis
Description Gentamicin Sulfate is a white to light yellowish white powder.
Gentamicin Sulfate is very soluble in water, and practically insoluble in ethanol or in ether.
Identification (1) Dissolve 50 mg of Gentamicin Sulfate in 1 mL of water, and add 2 drops of the solution
of 1-naphthol in ethanol(1 in 500). Gently superimpose
the solution on 1 mL of sulfuric acid: a purple-blue color
develops at the zone of contact.
(2) Dissolve 0.1 g each of Gentamicin Sulfate and
Gentamicin Sulfate RS in 100 mL of 0.1 mol/L phosphate buffer (pH 8.0), and use these solutions as the test
solution and the standard solution. Perform the test with
these solutions as directed under Thin-layer Chromato-
Content Ratio of Gentamicins Weigh accurately an

amount of Gentamicin Sulfate and Gentamicin Sulfate
RS, dissolve in water and make a solution so that each
mL contains 0.65 mg (potency). To 10 mL of each of
these solutions add 5 mL of isopropanol and 4 mL of the
O-Phthalaldehyde solution, mix, and add isopropanol to
obtain 25 mL of solutions. Heat at 60 C in water bath
for 15 minutes, and cool. The resulting solutions are used
as the test solution and the standard solution. Perform the
test with each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and obtain
the peak areas, Af of gentamicins (gentamicin C1: 25
50 %, gentamicin C1a : 10 - 35 %, gentamicin C2 and
C2a : 25 55 %).
Content ratio of gentamicin C1, C1a, C2 and C2a (%)

Af
=
100
AS
Af : the peak area response corresponding to the particular gentamicin
AS : the sum of the area responses of all four peaks
KP 9 455
octadecylsilanized silica gel or fine ceramic particle for
liquid chromatography(5 ~ 10 m in particle diameter)
Mobile phase: Mix 700 mL of methanol, 250 mL of
water and 50 mL of glacial acetic acid. Dissolve 5 g of
sodium 1-heptanesulfonate in this solution.
Flow rate: about 1.5 mL per minute.
System suitability
with 10 L of the standard solution under the above operating conditions, the capacity factor determined from
the gentamicin C1 peak is between 2 and 7, the column
efficiency determined from the gentamicin C2 peak is
mot less than 1200 theoretical plates, and the resolution,
R, between any two peaks is not less than 1.25. The elution order is gentanicin C1, gentanicin C1a, gentamicin
C2a, and gentamicin C2.
times with 10 L of the standard solution under the operating conditions, the relative standard deviation of any
peak area is not more than 2.0 %.
6.0 g Glucose
2.0 g
Yeast extract 3.0 g Sodium chloride
10.0 g
Meat extract 1.5 g Agar
13.0 20.0 g
Water
1000 mL
(2) Agar medium for transferring test organisms- Use
2 under Microbial Assay for
the medium in I 2 1) (2)
Antibiotics.
(3) Test organism- Staphylococcus epidermidis ATCC
12228
(4) Weigh accurately an amount of Gentamicin Sulfate, equivalent to about 25 mg (potency) and dissolve in
solution containing 1 mg gentamicin per mL (potency)
and use the solution as the test stock solution. Take exactly a suitable amount of the test stock solution, add 0.1
mol/L phosphate buffer solution, pH 8.0 to make solutions so that each mL contains 4 g (potency) and 1 g
(potency), and use these solutions as the high concentration test solution and low concentration test solution, respectively. Separately, weigh accurately an amount of
Gentamicin Sulfate RS, equivalent to about 25 mg (potency) and dissolve in 0.1 mol/L phosphate buffer solution, pH 8.0 to make the solution containing 1 mg gentamicin per mL (potency) and use the solution as the
standard stock solution. Take exactly a suitable amount
of the standard stock solution, add 0.1 mol/L phosphate
contains 4 g (potency) and 1 g (potency), and use
these solutions as the high concentration standard solution and low concentration standard solution, respectively. Perform the test with these solutions according to the
Cylinder-plate method as directed under Microbial Assay
for Antibiotics.
Glibenclamide
Cl
O
C
O
NHCH2CH2
O
H
N
H
N
O
OCH3
C23H28ClN3O5S: 494.00
Glibenclamide, when dried, contains not less than 98.5%
and not more than 101.0% of glibenclamide
(C23H28ClN3O5S).
Description Glibenclamide is a white to pale yellowish
Glibenclamide is freely soluble in dimethylformamide,
sparingly soluble in chloroform, slightly soluble in methanol or in ethanol and practically insoluble in water or
in ether.
solutions of Glinbenclamide and Glibenclamide RS in
methanol (1 in 10000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared absorption spectra of Glibenclamide and Glibenclamide RS, previously dried, as
(3) Perform the test with Glibenclamide as directed
under the Flame Coloration Test (2): a green color is observed.
Purity (1) Heavy metalsProceed with 1.0 g of Glibenclamide according to Method 2 and perform the test.
(2) Related substancesDissolve 0.20 g of Glibenclamide in 20 mL of chloroform and use this solution as
add chloroform to make exactly 50 mL. Pipet 2.5 mL of
this solution, add chloroform to make exactly 10 mL and
plate of silica gel with fluorescent indicator for Thin-

layer chromatoghraphy. Develop the plate with a mixture
of n-propanol, chloroform and diluted ammonia TS (4 in
5) (11 : 7 : 2) to a distance of about 12 cm and air-dry the
254 nm): the spots other than the principal spot from the
standard solution.
hours).
Assay Weigh accurately about 0.9 g of Glibenclamide,
previously dried, dissolve in 50 mL of dimethylformamide and titrate with 0.1 mol/L sodium hydroxide VS
(indicator: 3 drops of phenolphthalein TS). Perform a
black determination with a solution prepared by adding
18 mL of water to 50 mL of dimethylformamide and

= 49.40 mg of C23H28ClN3O5S
Gliclazide
N
N
H
N
H
H3C
C15H21N3O3S: 323.41
Gliclazide contains not less than 99.0% and not more
than 101.0% of gliclazide (C15H21N3O3S), calculated on
the dried basis.
Description Gliclazide is a white power.
Gliclazide is freely soluble in dichloromethane, sparingly
soluble in acetone, slightly soluble in alcohol and practically insoluble in water.
Identification Determine the infrared spectra of Gliclazide and Gliclazide RS as directed in the potassium
Purity (1) Heavy metalsProceed with 1.5 g of Gliclazide according to Method 2, and perform the test. Prepare the control solution with 1.5 mL of standard lead solution (not more than 10 ppm).
(2) Related substance IWeigh accurately 0.4 g of
Gliclazide, dissolve in 2.5 mL of dimethylsulfoxide, add
water to make exactly 10 mL, mix by shaking for 10 minutes, allow the solution to stand at 4 C for 30 minutes,
filter and use the filtrate as the test solution. Weigh 20.0
mg of gliclazide related substance I RS [2-nitrosooctahydrocyclopenta[c]pyrrole] and add dimethylsulfoxide to make exactly 100 mL. To 1.0 mL of this solution,
add 12 mL of dimethylsulfoxide and water to make exactly 50 mL, and use this solution as the standard solution (1). To 1.0 mL of the standard solution (1), add 12
mL of dimethylsulfoxide and water to make exactly 50
mL, and use this solution as the standard solution (2).
the standard solution (2) as directed under the Liquid
directed in the Related substance under the Purity: the
area of the related substance I peak obtained from the
test solution is not greater than that from the standard solution (2) (2 ppm).
Gliclazide, dissolve in 23 mL of acetonitrile, add water
to make exactly 50 mL, and use this solution as the test
solution. To 1.0 mL of the test solution and add a mixture
of water and acetonitrile (55 : 45) to make exactly 100
mL. Pipet 10.0 mL of the solution, add a mixture of water and acetonitrile (55 : 45) to make exactly 100 mL,
and use this solution as the standard solution (1). Dissolve 5 mg of Gliclazide and 15 mg of gliclazide related
substance II RS [1-(hexahydrocyclopenta[c] pyrrol2(1H)-yl)-3-[(2-methylphenyl)sulfonyl]urea] in 23 mL of
acetonitrile, add water to make 50 mL, pipet 1.0 mL of
this solution, add a mixture of water and acetonitrile (55 :
standard solution (2). Dissolve 10.0 mg of gliclazide related substance II RS in 45 mL of acetonitrile and add
water to make exactly 100 mL, pipet 1.0 mL of this solution, add a mixture of water and acetonitrile (55 : 45) to
make exactly 100 mL and use this solution as the standard solution (3). Perform the test with 20 L each of the
test solution, the standard solution (1) and (3) as directed
under the Liquid Chromatography according to the following operating conditions and determine the area of
peaks from the these solutions: the peak area corresponding to the related substance II obtained from the test solution is not greater than the area of the principal peak
obtained from the standard solution (3) (0.1%), the area
of any peak other than the principal peak or the related
substance II peak from the test solution is not greater
than the area of the principal peak from the standard solution (1) (0.1%), and total area of these other peaks
from the test solution is not greater than twice the area of
the principal peak from the standard solution (1) (0.2%).
Disregard any peak having the area not more than 0.2
times the area of the principal peak from the standard solution (1).
Column: A stainless steel column about 4 mm in in-
KP 9 457
side diameter and about 25 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 m in
particle diameter).
Mobile phase: A mixture of water, acetonitrile, trifluoroacetic acid and triethylamine (55:45:0.1:0.1).
System suitability
System performance: Proceed with 20 L of the
standard solution (2) under the above operating conditions and adjust the sensitivity of the system so that the
heights of the two principal peaks obtained from the
standard solution (2) are not less than 50 % of the full
scale of the recorder. Under this operating condition, the
resolution between the two principal peaks is not less
than 1.8.
hours).
Residue on Ignition
Assay Weigh accurately about 0.25 g of Gliclazide,

dissolve in 50 mL of glacial acetic acid and titrate with
0.1 mol/L perchlroic acid VS (potentiometric titration,
Each mL of perchloric acid VS

= 32.34 mg of C15H21N3O3S
Gliquidone
O
O
S
NH
MeO
NH
N
Me
Me
C27H33N3O6S: 527.63
Gliquidone contains, when dried, not less than 98.5%
and not more than 101.5% of gliquidone (C27H33N3O6S).
Description Gliquidone is a white powder.
Gliquidone is freely soluble in dimethylformamide, soluble in acetone, slightly soluble in ethanol or in methanol, and practically insoluble in water.
Identification (1) Dissolve 30 mg of Gliquidone in
methanol, evaporate the solvent using a rotary evaporator
and dry the residue at 50 C under vacuum. Determine
the infrared spectra of the dried residue and Gliquidone

(2) When proceed as directed in the Related substances under the Purity, the Rf value of the principal
spot from the test solution corresponds that from the
Melting Point
Purity (1) Heavy metalsProceed with 1.0 g of Gliquidone according to Method 2, and perform the test.
(2) Related substancesDissolve 1.0 g each of Gliquidone and Gliquidone RS in 10 mL each of a mixture
of methanol and dichloromethane (1 : 1) and use these
solutions as the test solution and the standard solution (1),
respectively. Dilute the standard solution (1) with a mixture of methanol and dichloromethane (1 : 1) to render
the concentration of 0.0030w/v% and use this solution as
the standard solution (2). Separately, dissolve 3.0 mg of
gliquidone sulfonamide RS in 100 mL of a mixture of
methanol and dichloromethane (1 : 1) and use this solution as the standard solution (3). Mix equal volumes of
the standard solution (2) and (3), and use the mixture as
the standard solution (4). Perform the test with the test
solution and the standard solutions as directed under the
solution, the standard solutions (1), (2), (3) and (4) on a
cyclohexane, chloroform, ethanol and glacial acetic acid
the plate. Examine the plate under ultraviolet light: the
spot corresponding to gliquidone sulfonamide from the
test solution is not more intense than that from the standard solution (3) (0.3%) and any other secondary spot
from the test solution is not more intense than that from
the standard solution (2) (0.3%). The test is valid when
two principal spots are clearly separated with each other
in the chromatogram obtained from the standard solution
(4).
constant mass).
Assay Weigh accurately 0.3 g of Gliquidone, previously dried, dissolve in 70 mL of dimethylformamide and titrate immediately with 0.1 mol/L of tetrabutyl ammonium hydroxide VS (indicator: 0.05 mL of 0.3w/v%
thymol blue in methanol) until the color of the solution
changes to blue. Perform a blank determination and
make any necessany correction.
Each ml of 0.1 mol/L tetrabutyl ammonium hydroxide

VS = 52.76 mg of C27H33N3O6S.
KP 9 459
ethanol and boil under a reflux condenser: the solution is
clear.
(8) Soluble starch and sulfiteDissolve 1.0 g of
Glucose in 10 mL of water and add 1 drop of iodine TS:
a yellow color is observed.
Glucose
CH2OH
H
O
H
OH
OH

hours).
OH
HO
D-Glucopyranose
C6H12O6: 180.16
Glucose is -D-glucopyranose, -D-glucopyranose or a

mixture of them.
Glucose, when dried, contains not less than 99.5% and
not more than 101.0% of glucose [D-glucopyranose
(C6H12O6)].
Description Glucose is a white crystals or crystalline
powder, is odorless and has a sweet taste.
Glucose is freely soluble in water, soluble in hot ethanol,
ether.
Identification Add 2 to 3 drops of a solution of Glucose (1 in 20) to 5 mL of boiling Fehling's TS: a red precipitate is produced.
Purity (1) Clarity and color of solutionAdd 25.0 g
of Glucose to 30 mL of water in a Nessler tube, warm at
60 C in a water-bath until solution is obtained, cool and
add water to make 50 mL: the solution is clear and has
no more color than the following control solution.
Control solutionTake a mixture of 1.0 mL of cobaltous chloride stock CS, 3.0 mL of ferric chloride stock
CS and 2.0 mL of cupric sulfate stock CS, add water to
make 10.0 mL. Pipet 3.0 mL of this solution and add water to make 50 mL.
(2) AcidDissolve 5.0 g of Glucose in 50 mL of
freshly boiled and cooled water and add 3 drops of phenolphthalein TS and 0.60 mL of 0.01 mol/L sodium hydroxide VS: a red color is observed.
(3) ChloridePerform the test with 2.0 g of Glucose.
hydrochloric acid VS (not more than 0.018%).
(4) SulfatePerform the test with 2.0 g of Glucose.
(5) Heavy metalsProceed with 5.0 g of Glucose
according to Method 2 and perform the test. Prepare
(6) ArsenicDissolve 1.5 g of Glucose in 5 mL of
water, add 5 mL of dilute sulfuric acid and 1 mL of bromine TS, heat in a water-bath for 5 minutes and concentrate to 5 mL. After cooling, perform the test with this solution as the test solution (not more than 1.3 ppm).
(7) DextrinTake 1.0 g of Glucose, add 20 mL of

Assay Weigh accurately about 10 g of Glucose, previously dried, dissolve in 0.2 mL of ammonia TS and
water to make exactly 100 mL, allow to stand for 30 minutes and determine the optical rotation, D, of this solution at 20 1 C in a 100-mm cell as directed under the
Optical Rotation Determination.
Amount (mg) of C6H12O6 = D 1895.4

Glucose Injection
Glucose Injection is an aqueous solution for injection.
Glucose Injection contains not less than 95.0% and not
more than 105.0% of the labeled amount of glucose
(C6H12O6: 180.16).
Method of Preparation Prepare as directed under Injections, with Glucose.
No preservative is added.
Description Glucose Injection is a clear, colorless liquid. Glucose has a sweet taste. It occurs as a colorless to
pale yellow, clear liquid when its labeled concentration
exceeds 40%.
Identification Measure a volume of Glucose Injection,
equivalent to 0.1 g of glucose according to the labeled
amount and, if necessary, add water or evaporate on a
water-bath to make of 2 mL. Add 2 to 3 drops of this solution to 5 mL of boiling Fehling's TS: a red precipitate
is produced.
pH Between 3.5 and 6.5. In the case where the labeled
concentration of the injection exceeds 5%, dilute to 5%
with water before the test.
Purity 5-Hydroxymethylfurfural and related substancesMeasure exactly a volume of Glucose Injection,
equivalent to 2.5 g of glucose according to the labeled
amount and add water to make exactly 100 mL. Determine the absorbance of this solution at 284 nm as directed under the Ultraviolet-visible Spectrophotometry: it

Baterial Endotoxins
Glucose Injection.
pH Dissolve 1 g of Glutamine in 50 mL of water: the

pH of this solution is between 4.0 and 6.0.

It

Assay Measure accurately a volume of Glucose Injection, equivalent to about 4 g of glucose (C6H12O6) and
add 0.2 mL of ammonia TS and water to make exactly
100 mL. Shake the solution well, allow to stand for 30
minutes and determine the optical rotation, D, at 20 1
C in a 100-mm cell as directed under the optical Rotation Determination.
Amount (mg) of glucose (C6H12O6) = D 1895.4

Packaging and Storage Preserve in hermetic containers. Plastic containers for aqueous injections may be used.
Glutamine
O
H2N
OH
H
L-glutamine
NH2
C5H10N2O3: 146.15
Glutamine contains not less than 98.5% and not more

than 101.5% of L-glutamine (C5H10N2O3), calculated on
the dried basis.
Description Glutamine is a white crystal or crystalline
powder, is odorless and has a faint, characteristic taste.
Glutamine is soluble in water and practically insoluble in
Purity (1) ChlorideProceed with 0.35 g of Glutamine and perform the test. Use 0.50 mL of 0.01 mol/L
hydrochloric acid VS as the control solution (not more
than 0.05%).
(2) SulfateProceed with 0.2 g of Glutamine and
perform the test. Use 0.25 mL of 0.005 mol/L sulfuric acid VS as the control solution (not more than 0.03%).
(3) IronDissolve 0.333 g of Glutamine in water to
make 45 mL, add 2 mL of hydrochloric acid as the test
solution. To 1 mL of standard iron solution, add water to
make 45 mL, add 2 mL of hydrochloric acid and use this
solution as the standard solution. Add 50 mg each of
ammonium peroxydisulfate crystal and 3 mL of 30%
ammonium thiocyanate solution to the test solution and
the standard solution: the color obtained from the test solution is not darker than that from the control solution
(30 ppm).
(4) Heavy metalsProceed with 1.0 g of Glutamine
(5) Related substancesDissolve 0.10 g of Glutamine in 10 mL of water and use this solution as the test
solution. Dissolve 50 mg of Glutamine RS in water to
make exactly 100 mL, pipet 5.0 mL of this solution, add
L each of the test solution and standard solution on a
plate of silica gel for thin-layer chromatography. Develop the ploate with a mixture of n-butanol, water and glacial acetic acid (3:1:1) to a distance of about 10 cm, and
dry the plate at 80 C for 30 minutes. Spray the plate
evenly with a solution, prepared by dissolving 0.2 g of
ninhydrin in 100 mL of a mixture of n-butanol and 2
mol/L acetic acid (95:5), and heat the plate at 80 C for
10 minutes: the spots other than the principal spot obtained from the test solution is not more intense than that
hours).
Identification Determine the infrared spectra of Glutamine and Glutamine RS as directed in the potassium
Assay Weigh accurately about 0.15 g of Glutamine, add

3 mL of formic acid and 50 mL of glacial acetic acid to
dissolve and titrate with 0.1 mol/L perchloric acid VS

+ 7.3 (2 g, after drying, water, 50 mL, 100 mm).

= 14.615 mg of C5H10N2O3
KP 9 461
tainers.
tion has no more color than the following control solution.
Glycerin
Glycerol
C3H8O3: 92.09
Glycerin contains not less than 84.0% and not more than
87.0% of glycerin (C3H8O3) (by specific gravity).
Description Glycerin is a clear, colorless, viscous liquid, is odorless and has a sweet taste.
Glycerin is miscible with water or with ethanol.
Glycerin is very slightly soluble in ether.
Glycerin is hygroscopic.
under Concentrated Glycerin.
Refractive index
nD20 : Between 1.449 and 1.454.
Specific Gravity
20
d 20
: Between 1.221 and 1.230.
Purity Proceed as directed in the Purity under Concentrated Glycerin.

Residue on Ignition Proceed as directed in the Residue on ignition under Concentrated Glycerin.
Concentrated Glycerin
Concentrated Glycerol
C3H8O3: 92.09
Concentrated Glycerin contains not less than 98.0% and

not more than 101.0% of glycerin (C3H8O3) (by specific
gravity).
Description Concentrated Glycerin is a clear, colorless
and viscous liquid, is odorless and has a sweet taste.
Concentrated Glycerin is miscible with water or with
ethanol.
Concentrated Glycerin is very slightly soluble in ether.
Concentrated Glycerin is hygroscopic.
Identification Heat 2 to 3 drops of Concentrated Glycerin with 0.5 g of potassium bisulfate: the odor of
acrolein is perceptible.
Refractive index
nD20 : Not less than 1.470
Specific Gravity
20
: Not less than 1.258.
d 20
Control solutionPipet 0.40 mL of ferric chloride

colorimetric stock solution into a Nessler tube and add
(2) Acidity or alkalinityTo 2 mL of Concentrated
Glycerin, add 8 mL of water and mix: the solution is neutral.
(3) ChlorideTake 10.0 g of Concentrated Glycerin
0.30 mL of 10 mmol/L hydrochloric acid VS (not more
than 0.001%).
(4) SulfateTake 10.0 g of Concentrated Glycerin
0.40 mL of 5 mmol/L sulfuric acid VS (not more than
0.002%).
(5) AmmoniumTake 5 mL of Concentrated Glycerin, add 5 mL of a solution of sodium hydroxide (1 in 10)
and boil: the gas evolved does not change moistened red
litmus paper to blue.
(6) Heavy metalsProceed with 5.0 g of Concentrated Glycerin according to Method 1 and perform the
(7) CalciumTake 5 mL of the solution obtained in
(2), add 3 drops of ammonium oxalate TS: the solution
remains unchanged.
Concentrated Glycerin according to Method 1 and perform the test (not more than 2 ppm).
(9) Acrolein, glucose or other reducing substancesTake 1.0 g of Concentrated Glycerin, add 1 mL
of ammonia TS, mix and warm in a water-bath at 60
for 5 minutes: no yellow color is produced. Take the solution out of the water-bath, add 3 drops of silver nitrate
TS immediately and allow to stand in a dark place for 5
minutes: the color of the solution does not change and no
turbidity is observed.
(10) Diethylene glycol and related substances
Weigh accurately about 5 g of Concentrated Glycerin,
add water to make 100 mL and use this solution as the
test solution. Separately, dissolve suitable amount of Diethylene Glycol RS in water to render the concentration of
0.05 mg in 1 mL and use this solution as the standard solution. Perform the test with exactly 0.5 L of the test
and standard solution by the following condition as directed under the Gas Chromatography. Determine the
peak areas diethylene glycol from the test solution, AT ,
and from the standard solution, AS . Amount of diethylene glycol, as calculated by the following equation, is
not more than 0.1%:
Amount (%) of diethylene glycol (C4H10O3)
=
Purity (1) ColorPlace 50 mL of Concentrated Glycerin in a Nessler tube and observe downward: the solu-
C S AT
100
CT AS
CS : Concentration of diethylene glycol in the stan-

dard solution (mg/mL)
CT : Concentration of diethylene glycol in the test solution (mg/mL)
In addition, determine the peak area ( Ai ) of diethylene
glycol or individual related substance, other than those
detected from the residual solvent in the test solution,
and the sum of all peak areas ( ATS ) in the test solution.
Amounts of individual related substances other than diethylene glycol, as calculated by the following equation,
are not more than 0.1% each and the sum of amount of
related substances, including diethylene glycol, is not
more than 1.0%.
Amount (%) of individual related substance
=
Ai
100
ATS
Ai : Peak area of diethylene glycol or individual related substance ( ATS ) other than those detected from the
residual solvent in the test solution
ATS : Total peak area in the test solution
Detector: A hydrogen flame ionization detector
Column: Coat the inside wall of a quartz tube, 0.53
mm in inside diameter and 30 m in length, to 3.0 m
thickness with 6% cyanopropylphenyl- and 94% dimethylpolysiloxan for gas chromatography
Column temperature: Start at 100 , increase to 220
C at 7.5 C per minute and keep at 220 for 4 minutes
about 220 C
about 250 C
Carrier gas: Helium
Flow rate: 38 cm/sec
Split ratio: About 1 : 10
System suitability
System performance: Take suitable amount of
Glycerin RS and diethylene glycol and dissolve in water
to render the concentration of 0.5 mg in 1 mL each. Perform the test with 0.5 L of the solution under the above
operating conditions. The resolution between the peaks
of glycerin and diethylene glycol is not less than 7.0.
times with 0.5 L of the standard solution under the
above operating conditions, the relative standard deviation of the peak of glycerin is not more than 15.0%.
(11) Fatty acids and estersMix 50 g of Concentrated Glycerin with 50 mL of freshly boiled and cooled
water, add 10 mL of 0.1 mol/L sodium hydroxide VS,
accurately measured, boil the mixture for 15 minutes,
cool and titrate the excess sodium hydroxide with 0.1
mol/L hydrochloric acid VS: not more than 3.0 mL of 0.1
mol/L sodium hydroxide VS is consumed (indicator: 3
drops of phenolphthalein TS). Perform a blank determination and make any necessary correction.
(12) Readily carbonizable substancesTake 5 mL
of Concentrated Glycerin, add carefully 5 mL of sulfuric
acid, mix gently at a temperature between 18 and
20 and allow to stand for 1 hour at room temperature: the solution has no more color than Matching Fluid
H.
Residue on Ignition Weigh accurately about 10 g of
Concentrated Glycerin in a tared crucible, heat to boiling
and fire to burn immediately. Cool, moisten the residue
with 1 to 2 drops of sulfuric acid and ignite cautiously to
constant weight: the weight of the residue is not more
than 0.01% .
Gramicidin
Gramicidin is the mixture of peptide substances having
antibacterial activity produced by the growth of Bacillus
brevis Dubos.
Gramicidin contains not less than 900 g (potency) per
mg of gramicidin, calculated on the dried basis.
Description Gramicidin occurs as a white to light yellowish white crystal or crystalline powder.
Gramicidin is freely soluble in ethanol or in methanol,
soluble in acetone or in dioxane, and practically insoluble in water.
Identification (1) To 10 mg of Gramicidin add 2mL
of 6 mol/L hydrochloric acid TS, and heat in a water bath
for 30 minutes with occasional stirring. After cooling,
neutralize with 6 mol/L sodium hydroxide TS, add 1 mL
of ninhydrinacetic acid TS and 0.5 mL of pyridine, and
heat for 2 minutes: a blue-purple to red-purple color develops.
of Gramicidin and Gramicidin RS in methanol (1 in
25000), as directed under Ultraviolet-visible Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wavelengths.
Melting Point Not less than 229 C (after drying)
of Gentamicin Sulfate in 10 mL of water is between 3.5
and 5.5.
KP 9 463
Assay The Turbidimetric method (1) Agar medium
for transferring testorganismPeptone
5.0 g
Potassium dihydrogen phosphate
2.0 g
Yeast extract
20.0 g
Polysorbate 80
0.1 g
Glucose
10.0 g
Agar
15.0 20.0 g
Water
1000 mL
(2) Liquid medium for suspending test organismsUse the culture medium in III 1 2) under Microbial Assay for Antibiotics.
(3) Test organism and preparation of the test organism suspension- Use Streptococcus faecium ATCC 10541
as test organism. Puncture the test organism in the agar
medium for transferring test organism, incubate, and
keep below 5 C. Transfering the organism is carried out
every week. Transfer the organism so obtained in 10 mL
of the liquid medium for suspending test organism, incubate at 37 C for 20 to 24 hours, and use this medium as
the test organism suspension. Before use, mix one mL of
this suspension and 100 mL of the liquid medium for
suspending test organism, and use this as the test organism suspension.
(4) Weigh accurately an amount of Gramicidin, dissolve, and dilute in ethanol(95 %) to make the test solution containing 0.0400 g (potency) per mL, and use this
an amount of Gramicidin RS, dissolve in ethanol (95 %)
to make the standard stock solution containing 1 mg (potency) per mL. Keep the standard solution at not exceeding 5 C and use within 30 days. Take exactly a suitable
amount of the standard stock solution, dilute in ethanol
(95 %) to make the standard solutions so that each mL
contains 0.0320, 0.0350, 0.0400, 0.0448 and 0.0500 g
(potency) respectively. To each of the test tube add 0.1
mL of the test solution and each of the standard solutions,
and perform the test according to the Turbidimetric method (III 6) as directed under Microbial Assay for Antibiotics.
Griseofulvin contains not less than 900 g (potency) per

mg of griseofulvin (C17H17ClO6), calculated on the dried
basis.
Description Griseofulvin is a white crystal or crystalline powder.
Griseofulvin is soluble in N,N-dimethylformamide,
slightly soluble in methanol and in ethanol, very slightly
soluble in ether, and practically insoluble in water.
Identification Determine the absorption spectra of the
solutions of Griseofulvin and Griseofulvin RS in ethanol
(1 in 100000), as directed under Ultraviolet-visible Spectrophotometry, both spectra exhibit similar intensities of
25
Specific Optical Rotation [ ]D : +348 ~ +364(0.25

g calculated on the dried basis, N,N-dimethylformamide,
25 mL, 200 mm)
Melting Point Between 217 and 224 C.
Purity Heavy metalsProceed with 1.0 g of Griseofulvin according to Method 1 and perform the test. Prepare the control solution with 2.5 mL of standard lead solution (not more than 25 ppm).
Assay Weigh accurately an amount of Griseofulvin and
Griseofulvin RS, equivalent to about 25 mg (potency),
dissolve each in 25 mL of methanol, add methanol to 5
mL of each solution to make exactly 50 mL and use these
Perform the test with each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following operating conditions
and obtain the peak areas of griseofulvin, AT and AS.
Amount [g (potency)] of griseofulvin (C17H17ClO6)

= Amount [g (potency)] of Griseofulvin RS
Griseofulvin
Cl
H3CO
H3CO
O
O
O
OCH3
CH3
C17H17ClO6HCl: 352.77
Griseofulvin is a substance having antifungal activity
produced by the growth of Penicillium griseofulvum.
AT
AS
with octadecylsilanized silica gel for liquid chromatography(5 ~ 10 m in particle diameter)
Mobile phase: 60 % methanol
time of griseofulvin is about 6 minutes.
Guaifenesin
H
OH
OCH 2CCH 2OH

OCH 3
and enantiomer
Guaiacol Glyceryl Ether
C10H14O4: 198.22
Guaifenesin, when dried, contains not less than 98.0%

and not more than 102.0% of guaifenesin (C10H14O4).
Description Guaifenesin is a white crystal or crystalline powder.
Guaifenesin is freely soluble in hot water or in ethanol,
soluble in chloroform, sparingly soluble in water and
slightly soluble in ether.
A solution of ethanol (1 in 20) shows no optical rotation.
Identification (1) Take 5 mL of Guaifenesin, add 1 mL
of formalin-sulfuric acid TS: a red-purple color is observed.
Guifenesin and Guaifenesin RS (1 in 50000) as directed
same wavelengths.
Guaifenesin and Guaifenesin RS, previously dried, as directed in the potassium bromide disk method under the
intensities of absorption at the same wavenumbers .
(5) Free guaiacolTake 1.0 g of Guaifenesin, add

exactly 25 mL of water, dissolve by warming, cool and
0.10 g of guaiacol in water to make exactly 1000 mL. Pipet 3.0 mL of this solution, add exactly 22 mL of water
and use this solution as the standard solution. To each of
the test solution and the standard solution, add 1.0 mL of
potassium ferricyanide TS and 5.0 mL of a solution of 4aminoantipyrine (1 in 200) and immediately after shaking for exactly 5 seconds, add a solution of sodium bicarbonate (1 in 1200) to make exactly 100 mL. Determine the absorbances of the test solution and the standard solution at 500 nm exactly 15 minutes after the addition of the 4-aminoantipyrin solution as directed under
the Ultraviolet-visible Spectrophotometry, using a solution, prepared in the same manner with 25 mL of water,
as the blank: the absorbance of the solution obtained
from the test solution is not greater than that from the
standard solution.
(6) Related substancesDissolve 1.0 g of Guaifenesin in 100 mL of ethanol and use this solution as the test
solution. Pipet 1.0 mL of the test solution, add water to
make exactly 200 mL and use this solution as the standard solution. Perform the test with the test solution and
of ether, ethanol and strong ammonia water (40 : 10 : 1)
evenly p-dimethylaminobenzaldehyde TS for spraying
on the plate and heat at 110 o C for 10 minutes: the spots
Melting Point Between 80 and 83 .

60 o C , 3 hours).
pH Dissolve 1.0 g of Guaifenesin in 100 mL of water:

the pH of the solution is between 5.0 and 7.0.

0.20 g of Guaifenesin in 10 mL of water: the solution is
(2) ChlorideDissolve 0.7 g of Guaifenesin in 25
mL of water by warming. Cool, add 6 mL of dilute nitric
this solution as the test solution. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS
Guaifenesin according to Method 3 and perform the test
(4) Heavy metalsDissolve 2.0 g of Guaifenesin in
25 mL of water by warming. Cool, add 2 mL of dilute
acetic acid and water to make 50 mL and perform the test
using this solution as the test solution. Prepare the control solution with 2.0 mL of standard lead solution (not
more than 10 ppm).
Assay Weigh accurately about 60 mg of Guaifenesin,

previously dried, dissolve in water to make exactly 100
mL. Pipet 5.0 mL of the solution and add water to make
exactly 100 mL. Determine the absorbance, A, of the solution at 273 nm as directed under the Ultraviolet-visible
Spectrophotometry.
Amount (mg) of guaifenesin (C10H14O4)

A
=
20000
117
KP 9 465
Guanethidine Sulfate
NH
N
CH2CH2NHC
H2SO4
NH2
Assay Weigh accurately about 0.5 g of Guanethidine

Sulfate, previously dried, dissolve in 100 mL of formic
acid and add 70 mL of a mixture of acetic anhydride and
glacial acetic acid (6 : 1) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
C10H22N4H2SO4: 296.39
Guanethidine Sulfate, when dried, contains not less than
98.5% and not more than 101.0% of guanethidine sulfate
(C10H22N4H2SO4).
Description Guanethidine Sulfate is a white crystal or
crystalline powder, is odorless or has a slight, characteristic odor and a bitter taste.
Guanethidine Sulfate is very soluble in formic acid, freely soluble in water and practically insoluble in ethanol or
in ether.
Melting pointBetween 251 C and 256 C (an evacuated sealed capillary tube, with decomposition).
Identification (1) Take 4 mL of a solution of Guanethidine Sulfate (1 in 4000), add 2 mL of -naphthol TS,
1 mL of diacetyl TS and 15 mL of water and allow to
stand for 30 minutes: a red color is observed.
(2) Determine the infrared absorption spectra of Guanethidine Sulfate and Guanethidine Sulfate RS, previously dried, as directed in the potassium bromide disk
same wavenumbers .
(3) A solution of Guanethidine Sulfate (1 in 10) responds to the Qualitative Tests for sulfate.
pH Dissolve 1.0 g of Guanethidine Sulfate in 50 mL of
water: the pH of the solution is between 4.7 and 5.7.
g of Guanethidine Sulfate in 50 mL of water: the solution
is clear and colorless.
(2) Methylisothiourea sulfateDissolve 2.0 g of
Guanethidine Sulfate in 80 mL of sodium hydroxide TS
and allow to stand for 10 minutes. Add 60 mL of hydrochloric acid, 2 g of sodium bromide and water to
make 200 mL. Then, to this solution, add 0.70 mL of
1/60 mol/L potassium bromate VS and 2 mL of zinc
iodide-starch paste TS: a blue color is observed.
(3) Heavy metalsProceed with 2.0 g of Guanethidine Sulfate according to Method 4 and perform the test.
hours).
Residue on Ignition

= 29.639 mg of C10H22N4H2SO4
tight containers.
Haloperidol
OH
F
COCH 2 CH 2 CH 2
Cl
C21H23ClFNO2: 375.86
Haloperidol, when dried, contains not less than 99.0%
and not more than 101.0% of haloperidol
(C21H23ClFNO2).
Description Haloperidol is a white to pale yellow crystal or powder.
Haloperidol is freely soluble in glacial acetic acid, soluble in chloroform, sparingly soluble in methanol,
slightly soluble in isopropanol or in dehydrated ethanol
Identification (1) Dissolve 30 mg each of Haloperidol
and Haloperidol RS in 100 mL of isopropanol. Add 10
mL of 0.1 mol/L hydrochloric acid TS and isopropanol in
5 mL of these solutions to make 100 mL. Determine the
Ultraviolet-visible absorption Spectrophotometry according to the operating conditions: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Haloperidol and
Haloperidol RS as directed in the potassium bromide
disk method under the Infrared Spectrophotometry according to the operating conditions: both spectra exhibit
Purity (1) SulfateTake 1.0 g of Haloperidol, add 50
mL of water, shake and filter. Take 25 mL of the filtrate,
solution. Prepare the control solution with 0.50 mL of 5
mmol/L sulfuric acid VS (not more than 0.048%).
(2) Heavy metalsProceed with 1.0 g of Haloperi-

dol according to Method 2 and perform the test. Prepare
(3) Related substanceDissolve 25 mg of Haloperidol in 50 mL of mobile phase, use this solution as the test
solution. Pipet exactly 1 mL of this solution, add the mobile phase to make exactly 200 mL, use this solution as
the standard solution. Pipet exactly 10 L each of test
solution and standard solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area of both solutions by the
automatic integration method: the area of peak other than
the area of Haloperidol from the test solution is not larger than 2 times the peak area of the Haloperidol from the
standard solution. Peak areas of about 0.15, 1.2 and 2.6
in the relative retention time to Haloperidol are the values multiplied the area determined according to the automatic integration method by sensitivity factor, 0.75,
1.47 and 0.76, respectively.
Assay Weigh accurately about 0.6 g of Haloperidol,

acid and titrate with 0.1 mol/L perchloric acid VS (indicator: 1 drop of methylrosaniline chloride TS). Perform a
Detector: Ultraviolet-visible absorption Photometry
diameter and 15 cm in length, packed with octadecylsylanized silica gel for Liquid Chromatography (5 m in
particle diameter).
Column temperature: A constant temperature at about
40 C.
Mobile phase: Dissolve 2.95 g of sodium citrate in
900 mL of water, add dilute hydrochloric acid to adjust
pH 3.3, add water to make 1000 mL. Add 700 mL of methanol in 300 mL of this solution, add 1 g of sodium
lauryl sulfate, and dissolve.
Flow rate: Adjust to about 9 minutes of the retention
time of Haloperidol.
System suitability
Test for required detection: Weigh exactly 5 mL of
standard solution, add the mobile phase to make 25 mL.
The peak area of Haloperidol obtained from 10 L of
this solution is between 15 and 25% of the peak area of
Haloperidol obtained from the standard solution.
System performance: Perform the test with 10 uL
of the standard solution according to the above operating
conditions: the theoretical plate numbers is not less than
4000 and the symmetric factor is not more than 2.0.
System repeatability: Perform the test 6 times with 10 uL
of the standard solution according to the above operating
conditions: the relative standard deviation of Haloperidol
peak area is not more than 2.0%.
as the retention time of Haloperidol after the solvent
peak.
Method of Preparation Prepare as directed under Solutions, with Haloperidol. Haloperidol Oral Solution contains lactic acid as a solubilizing agents.

60 C, P2O5, 3 hours).

= 37.587 mg of C21H23ClFNO2
tight containers.
Haloperidol Oral Solution

Haloperidol Oral Solution contains not less than 90.0%
and not more than 110.0% of the labeled amount of haloperidol (C21H23ClFNO2: 375.86).
Identification Determine the ultraviolet absorption

spectrum of the test solution, prepared in the Assay: it
exhibit maxima at 245 2 nm.
pH
Assay Transfer an accurately measured volume of Haloperidol Oral Solution, equivalent to about 10 mg of haloperidol (C21H23ClFNO2), to a separator, add 20 mL of
dilute hydrochloric acid (1 in 20), extract with four 20
mL volumes of ether, combine the all extracts and wash
the ether layer with four 50 mL volumes of dilute hydrochloric acid (1 in 20). Discard the ether layer, add the
acid washing to the aqueous phase, filter the aqueous
phase through a pledget of cotton, add the dilute hydrocholoric acid (1 in 20) to the filtrate to make exactly 50
mL and mix. Pipet 10.0 mL of this solution, dilute with
10 mg of Haloperidol RS, add dilute hydrochloric acid (1
in 20) to make exactly 50 mL. Pipet 10.0 mL of this solution, dilute with methanol to make exactly 100 mL, use
this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the
standard solution, respectively, at absorption maximum
wavelength of about 245 nm as directed under the Ultraviolet-visible Spectrophotometry using a solution added
1 mL of dilute hydrochloric acid (1 in 20) in 10 mL of
methanol as the blank.
Amount (mg) of haloperidol (C21H23ClFNO2)

= Amount (mg) of Haloperidol RS
AT
AS
KP 9 467

tight containers.
Halothane
F
Cl
Br
and enantiomer
C2HBrClF3: 197.38
Halothane contains not less than 0.008% and not more

than 0.012% of Thymol as a stabilizer.
Description Halothane is a clear, colorless and mobile
liquid.
Halothane is miscible with ethanol, with ether or with
isooctane.
Halothane is slightly soluble in water.
Halothane is a volatile, nonflammable liquid and setting
fire to its heated vapor does not support combustion.
Halothane is affected by light.
Refractive index nD20 : Between 1.369 and 1.371.
Identification Transfer about 3 L each of Halothane
and Halothane RS to gas cells having light path, 10 cm in
length and determine the infrared absorption spectra as
directed in the gas sampling method under the Infrared
Specific Gravity
20
: Between 1.872 and 1.877.
d 20
Purity (1) Acid or alkaliShake 60 mL of Halothane

with 60 mL of freshly boiled and cooled water vigorously for 3 minutes. Separate the water layer and use this solution as the test solution. To 20 mL of the test solution,
add 1 drop of bromocresol purple TS and 0.10 mL of
0.01 mol/L sodium hydroxide VS: a red-purple color is
observed. To 20 mL of the test solution, add 1 drop of
bromocresol purple TS and 0.6 mL of 0.01 mol/L hydrochloric acid VS: a yellow color is observed.
(2) Halide and halogenTo 5 mL of the test solution obtained in (1), add 1 drop of nitric acid and 0.20
mL of silver nitrate TS: no turbidity is produced. To 10
mL of the test solution obtained in (1), add 1 mL of potassium iodide TS and 2 drops of starch TS and allow to
stand for 5 minutes: a blue color is not observed.
(3) PhosgeneTransfer 50 mL of Halothane to a
dried conical flask, suspend a strip of phosgene test paper vertically inside the flask with the lower end about
10 mm above the surface of the liquid, insert the stopper
and allow to stand in a dark place for 20 to 24 hours: the
test paper shows no yellow color.
(4) Residue on evaporationPipet exactly 50 mL of
Halothane, evaporate on a water-bath and dry the residue
at 105C for 2 hours: the amount of the residue is not

more than 1.0 mg.
(5) Volatile related substancesTake 100 mL of Halothane, add exactly 5.0 L of the internal standard and
use this solution as the test solution. Perform the test
with 5 L of the test solution as directed under the Gas
Chromatography and determine each peak area by the
automatic integration method: the total area of the peaks
other than those of Halothane and the internal standard is
not larger than the peak area of the internal standard.
Internal standard substance1,1,2-trichloro-1,2,2trifluoro-ethane.
and 3 m in length, at the first 2 m from the injection port,
having macrogol 400 coated in the ratio of 30% on siliceous earth for gas chromatography (180 m to 250 m
in particle diameter) and at the remaining 1 m, having
dinonyl phthalate coated in the ratio of 30% on siliceous
earth for gas chromatography (180 m to 250 m in particle diameter).
about 50 o C .
time of the internal standard is 2 minutes to 3 minutes.
System suitability
System performance: Mix 3 mL of Halothane and
1 mL of the internal standard. When the procedure is run
with 1 L of this solution, as directed under the above
operating conditions, the internal standard and Halothane
are eluted in this order with a resolution between their
Detection sensitivity: Adjust the detection sensitivity so that the peak height of the internal standard obtained from 5 L of the test solution composes 30% to
70% of the full scale.
the retention time of Halothane.
Distilling Range Not less than 95 vol% distils within a
1 C range between 49 C and 51 C.
Thymol To 0.50 mL of Halothane, add 5.0 mL of
isooctane and 5.0 mL of titanium dioxide TS, shake vigorously for 30 seconds and allow to stand: the separated
upper layer has more color than the following control solution A and has no more color than the following control
solution B.
Control solutionDissolve 0.225 g of Thymol RS in

isooctane to make exactly 100 mL. Take 10 mL each of
this solution, accurately measured, add isooctane to make
exactly 150 mL and 100 mL, respectively. Proceed with
0.50 mL each of these solutions in the same manner as
Halothane and use the separated upper layers obtained

from the control solutions A and B, respectively.
tight containers. Store at a temperature not exceeding 30
C.
Haloxazolam
O
H
N
Br
F
O
and enantiomer
C17H14BrFN2O2: 377.21
Haloxazolam, when dried, contains not less than 99.0%
and not more than 101.0% of haloxazolam
(C17H14BrFN2O2).
Description Haloxazolam is a white crystal or crystalline powder and is odorless and tasteless.
Haloxazolam is freely soluble in glacial acetic acid, sparingly soluble in acetonitrile, in methanol or in dehydrated ethanol, slightly soluble in ether and practically
insoluble in water.
Identification (1) Dissolve 10 mg of Haloxazolam in
10 mL of methanol, add 1 drop of hydrochloric acid under ultraviolet light (main wavelength: 365 nm): the solution shows a yellow-green fluorescence. To this solution, add 1 mL of sodium hydroxide TS: the fluorescence
disappears immediately.
(2) Prepare the test solution with 50 mg of Haloxazolam as directed under the Oxygen Flask Combustion Method, using a mixture of 20 mL of dilute sodium hydroxide TS and 1 mL of strong hydrogen peroxide water as an
absorbing liquid: the test solution responds to the Qualitative Tests for bromide and for fluoride.
Haloxazolam and Haloxazolam RS in methanol (1 in
(4) Determine the infrared spectra of Haloxazolam
and Haloxazolam RS, previously dried, as directed in the
%
Absorbance E11cm
(247 nm)
(10 mg, methanol, 1000 mL).
Between 390 and 410

0.10 g of Haloxazolam in 20 mL of dehydrated ethanol:
(2) Soluble halidesTake 1.0 g of Haloxazolam, add
50 mL of water, allow to stand for 1 hour with occasional
shaking and filter. To 25 mL of the filtrate, add 6 mL of
dilute nitric acid and water to make 50 mL and use this
solution as the test solution. Perform the test with this solution as directed under the Chloride Limit Test. Prepare
the control solution with 0.10 mL of 0.01 mol/L hydrochloric acid (Cl: not more than 0.0071%).
(3) Heavy metalsProceed with 1.0 g of Haloxazolam according to Method 2 and perform the test. Prepare
(4) ArsenicTake 1.0 g of Haloxazolam in a decomposition flask, add 5 mL of nitric acid and 2 mL of
sulfuric acid, place a small funnel on the mouth of the
flask and heat carefully until white fumes are evolved.
After cooling, add 2 mL of nitric acid, heat, repeat this
procedure twice, add several 2 mL of strong hydrogen
peroxide water and heat until the solution is colorless to
pale yellow. After cooling, add 2 mL of a saturated solution of ammonium oxalate and heat until white fumes are
evolved. After cooling, add water to make 5 mL and perform the test with this solution: the solution has no more
color than the following control solution (not more than
2 ppm).
Control solution-Proceed in the same manner as

above without using Haloxazolam, add 2.0 mL of standard arsenic solution and water to make 5 mL and proceed in the same manner as the test solution.
(5) Related substancesDissolve 0.10 g of Haloxazolam in 100 mL of acetonitrile and use this solution as
add acetonitrile to make exactly 100 mL and use this solution as the standard solution. Perform the test with 10
both solutions by the automatic integration method: the
total area of all peaks other than the area of the Haloxazolam from the test solution is not larger than the peak
area of the Haloxazolam from the standard solution.
Column temperature: A room temperature.`
Mobile phase: Dissolve 6.2 g of boric acid and 7.5 g
of potassium chloride in 900 mL of water, adjust the pH
with triethylamine to 8.5 and add water to make 1000
mL. To 3 volumes of this solution, add 2 volumes of ace-
KP 9 469
tonitrile.
time of Haloxazolam is about 10 minutes.
System suitability
Test for required detection: Weigh exactly 5 mL of
the standard solution, add acetonitrile to make exactly 50
mL. The peak area of Haloxazolam obtained from 10 L
of this solution is between 8 and 12% of the peak area of
Haloxazolam obtained from the standard solution.
System performance: Dissolve 10 mg each of Haloxazolam and Cloxazolam in 200 mL of acetonitrile.
When the precedure is run with 10 L of this solutions,
as directed under the above operating conditions, haloxazolam and cloxazolam are eluted in this order with a
resolution between their peaks being not less than 1.5.
times with 10 mL of standard solution according to the
above conditions: the relative deviation of the peak area
of haloxazolam is not more than 1.0%.
as the retention time of Haloxazolam after the solvent
peak.
hours).
powder or grains and is odorless.

Heparin Sodium is soluble in water and practically insoluble in ethanol or in ether.
Heparin Sodium is hygroscopic.
pH The pH of a solution of 1.0 g of Heparin Sodium in
100 mL of water is between 6.0 and 8.0.
g of Heparin Sodium in 20 mL of water: the solution is
clear and colorless to pale yellow.
(2) BariumDissolve 30 mg of Heparin Sodium in
3.0 mL of water and use this solution as the test solution.
To 1.0 mL of the test solution, add 3 drops of dilute sulfuric acid and allow to stand for 10 minutes: no turbidity
is produced.
(3) Total nitrogenWeigh accurately about 100 mg
of Heparin Sodium, previously dried at 60 C for 3 hours
under reduced pressure and perform the test as directed
under the Nitrogen Determination: the amount of nitrogen (N: 14.01) is not more than 3.0%.
(4) ProteinTake 1.0 mL of the test solution obtained in (2), add 5 drops of a solution of trichloroacetic
acid (1 in 5): neither a precipitate nor turbidity is produced.
Not more than 0.1% (1 g, plati-
Loss on Drying Not more than 10% (20 mg, in vacuum, 60 C, 3 hours).
Assay Weigh accurately about 0.5 g of Haloxazolam,

Residue on Ignition Not more than 40% (after drying,

20 mg).
Residue on Ignition
num crucible).

= 37.721 mg of C17H14BrFN2O2
tight containers.
Heparin Sodium
Heparin Sodium is obtained from the livers, the lungs
and the intestinal mucosa of healthy edible animals and
prolongs the clotting time of blood. Heparin Sodium obtained from the livers and the lungs contains not less than
110 heparin units per mg and that obtained from the intestinal mucosa contains not less than 130 heparin units
per mg.
Heparin Sodium, calculated on the dried basis, contains
not less than 90.0% and not more than 110.0% of the labeled units.
Label the name of the organ used as the starting material.
Description Heparin Sodium is white to grayish brown
Pyrogen Test Dissolve Heparin Sodium in isotonic sodium chloride solution so as to contain 1000 units per ml
according to the labeled units. Inject 2.0 mL of this solution per kg of the body weight of rabbits and perform the
test: it meets the requirement of the Pyrogen Test.
Assay (1) Substrate solutionDissolve 15 mg of Nbenzoyl-1-isoleucyl-Lglutamyl
(r-OR)-glycyl-Larginyl-p-nitroanilide hydrochloride acid in 20 mL of
water.
(2) Antithrombin III solutionDissolve human antithrombin III in water to make a solution containing 1
unit per mL.
(3) Activated blood coagulation factor X solution
Dissolve bovine activated blood coagulation factor X in
water to make a solution containing 0.426 units per mL.
(4) Buffer solutionDissolve 6.06 g of 2-amino-2hydroxymethyl-1,3-propanediol in 750 mL of water, adjust the pH to 8.4 with 1 mol/L hydrochloric acid TS, and
add water to make 1000 mL.
(5) Reaction stop solutionTo 20 mL of glacial acetic acid add water to make 40 mL.
(6) Heparin standard solutionsDissolve Heparin
Sodium RS in isotonic sodium chloride solution to make
a solution containing 10 units per mL, and use this solution as the standard stock solution. To 100 L of the
standard stock solution add the buffer solution to make

exactly 5 mL, and use this solution as the standard solution. Prepare the heparin standard solutions (1), (2), (3),
(4) and (5) by addition of antithrombin III solution, human normal plasma and the buffer solution to the standard solution as directed in the following table.
Heparin Standard Solutions
Buffer So- AntithHeparin
lutions rombins
concentra(L)
(L)
No.
tion
(Unit/mL)
(1)
(2)
(3)
(4)
(5)
0
0.02
0.04
0.06
0.08
800
700
600
500
400
100
100
100
100
100
Human
normal
blood
(L)
Standard
Solutions
(L)
100
100
100
100
100
0
100
200
300
400
(7) Test solutionWeigh accurately an adequate

amount of Heparin Sodium, dissolve in isotonic sodium
chloride solution, so that each mL contains about 0.5
units according to the labeled amount. To 100 L of this
solution add 100 L of antithrombin III solution, 100 L
of human normal plasma and 700 L of the buffer solution, and use this solution as the test solution.
(8) ProcedureTransfer 400 L of the test solution
to a test tube, and warm at 37 C for 4 minutes. Add 200
L of the activated blood coagulation factor X solution,
mix well, warm at 37 C for exactly 30 seconds, add 400
L of the substrate solution, previously warmed at 37,
and mix well. Allow the tube to stand at 37 C for exactly
3 minutes, add 600 L of the reaction stop solution, mix
immediately, and determine the absorbance at 405 nm,
using the blank solution prepared by addition of 600 L
of the reaction stop solution and 600 L of water to 400
L of the test solution. Proceed the same way with the
heparin standard solution (1), the heparin standard solution (2), the heparin standard solution (3), the heparin
standard solution (4) and the heparin standard solution
(5), and determine their absorbances at 405 nm.
(9) CalculationPlot the absorbances of the standard
solutions on the vertical axis and their heparin concentrations on the horizontal axis to prepare a calibration curve.
Determine the heparin concentration, C, to the test solution from its absorbance by using the calibration curve,
and calculate heparin units per mg of Heparin Sodium
from the following formula.
Units per mg of Heparin Sodium = C10 (b/a)
a : Amount (mg) of Heparin Sodium taken.
b: Total volume (mL) of isotonic sodium chloride solution used to dissolve the sample to make the solution
containing about 0.5 units per mL.
Heparin Sodium Injection

Heparin Sodium Injection is an aqueous solution for injection. Heparin Sodium Injection contains not less than
90.0% and not more than 110.0% of the labeled heparin
units.
Label the name of organ used as the starting material of
Heparin Sodium supplied for preparing Heparin Sodium
Injection.
Method of Preparation Dissolve Heparin Sodium in
isotonic sodium chloride solution and prepare as directed
under Injections.
Description Heparin Sodium Injection is a clear, colorless to pale yellow liquid.
Purity (1) BariumMeasure exactly a volume of Heparin Sodium Injection, equivalent to 3000 units of Heparin Sodium according to the labeled unit. Add water to
make 3.0 mL and use this solution as the test solution. To
1.0 mL of the test solution, add 3 drops of dilute sulfuric
acid and allow to stand for 10 minutes: no turbidity is
produced.
(2) ProteinProceed as directed in the Purity (4) under Heparin Sodium.
Bacterial Endotoxins Less than 0.0030 EU/unit of heparin.
Insoluble Particulate Matter for Injections
the requirement.
It meets

Assay Proceed as directed in the Assay under Heparin
Sodium, replacing the test solution indicated in (7) and
the calculation in (9) with the following.
(7) Test solutionMeasure exactly an adeqsuate portion of Heparin Sodium Injection according to the labeled units, dilute it with isotonic sodium chloride solution so that each mL contains about 0.5 units. To 100
L of this solution add 100 L of antithrombin III solution, 100 L of human normal plasma and 700 L of the
buffer solution, and use this solution as the test solution.
(9) CalculationPlot the absorbances of the standard
solutions on thevertical axis and their heparin concentrations on the horizontal axis to prepare a calibration curve.
Determine the heparin concentration, C, of the test solution from its absorbance by using the curve, and calcu-
KP 9 471
late heparin units per mL of Heparin Sodium Injection
from the following formula.
Units per mL of Heparin Sodium Injection
= C x 10 x (b/a)
a: Amount of sample (mL)
b: Total volume (mL) of isotonic sodium chloride solution used to dilute the sample to make the solution containing about 0.5 units per mL.
no red-purple color is produced.

(3) Other alkaloidsDissolve 0.15 g of Homatropine Hydrobromide in 3 mL of water and use this solution as the test solution.
(i) Take 1 mL of the test solution, add 2 to 3 drops of
tannic acid TS: no precipitate is produced.
(ii) Take 1 mL of the test solution, add 2 to 3 drops each
of dilute hydrochloric acid and platinic chloride TS: no
hours).
Homatropine Hydrobromide
H
O
O
NCH3
CH
HBr
OH
Assay Dissolve by warming about 0.4 g of Homatropine Hydrobromide in 60 mL of a mixture of acetic anhydride and glacial acetic acid (7 : 3). Cool and titrate
with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detdction Method in Titrimetry). Perform

= 35.626 mg of C16H21NO3.HBr
C16H21NO3HBr: 356.26
Homatropine Hydrobromide contains not less than
99.0% and not more than 101.0% of homatropine hydrobromide (Cl6H21NO3.HBr) calculated on the dried basis.
Description Homatropine Hydrobromide is a white
Homatropine is freely soluble in water, sparingly soluble
in ethanol, slightly soluble in glacial acetic acid, very
slightly soluble in acetic anhydride and practically insoluble in ether.
Homatropine Hydrobromide is affected by light.

tight containers.
Homochlorocyclizine
Hydrochloride
H
C
Cl
2 HCl
Identification (1) Take 5 mL of a solution of Homatropine Hydrobromide (1 in 20), add 2 to 3 drops of

iodine TS: a brown precipitate is produced.
(2) Dissolve 50 mg of Homatropine Hydrobromide in
5 mL of water and add 3 mL of picric acid TS: a yellow
precipitate is produced. Filter the precipitate, wash with
five 10 mL volumes of water and dry at 105 C for 2
(3) A solution of Homatropine Hydrobromide (1 in
20) responds to the Qualitative Tests for bromide.
Purity (1) AcidDissolve 1.0 g of Homatropine Hydrobromide in 20 mL of water and add 0.40 mL of 0.01
mol/L sodium hydroxide VS and 1 drop of methyl redmethylene blue TS: a green color develops.
(2) Atropine, hyoscyamine and scopolamineTake
10 mg of Homatropine Hydrobromide, add 5 drops of nitric acid, evaporate on a water-bath to dryness and cool.
Dissolve the residue in 1 mL of dimethylformamide and
add 5 to 6 drops of tetraethylammonium hydroxide TS:
CH3
and enantiomer
C19H23ClN22HCl: 387.77
Homochlorocyclizine Hydrochloride, when dried, contains not less than 98.0 and not more than 101.0% of
homochlorocyclizine hydrochloride (C19H23ClN22HCl).
Description Homochlorcyclizine Hydrochloride is a
white to pale brown crystal or powder, and is odorless.
Homochlorcyclizine Hydrochloride is very soluble in
water, freely soluble in glacial acetic acid, soluble in methanol or in ethanol, very slightly soluble in acetic anhydride and practically insoluble in ether.
Homochlorcyclizine Hydrochloride dissolves in 0.1
mol/L hydrochloric acid TS.
Homochlorcyclizine Hydrochloride is hygroscopic.
Homochlorcyclizine Hydrochloride is colored slightly by
light.

The water solution (I in 10) of Homochlorcyclizine Hydrochloride shows not optical rotation.
solutions of Homochlorocyclizine Hydrochloride and
Homochlorocyclizine Hydrochloride RS in 0.1 mol/L
hydrochloric acid TS (1 in 100000) as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit
similr intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Homochlorocyclizine Hydrochloride and Homochlorocyclizine Hydrochloride RS, previously dried, as directed in the potassium chloride disk method under Infrared Spectrophotometry: both spectra exhibit similr intensities of
(3) A solution of Homochlorocyclizine Hydrochloride (1 in 100) responds to the Qualitative Tests for chloride.
Purity (1) Heavy metalsProceed with 1.0 g of Homochlorocyclizine Hydrochloride according to Method 2
(2) Related substancesDissolve 0.10 g of Homochlorcyclizine Hydrochloride in 100 mL of mobile
phase and use this solution as the test solution. Measure
exactly 1 mL of the test solution and add mobile phase to
make exactly 100 mL and use this solution as the standard solution. Perform the test with exactly 10 L each
under Liquid Chromatography according to the following conditions, and determine the peak area by the automatic integration method: the area of the peaks other
than homochlorcyclizine obtained from the test solution
are not more than1/2 times the peak area of homochlorcyclizine from the standard solution, and the total area of
the peaks other than homochlorcyclizine from the test solution is not more than the peak area of homochlorcyclizine from the standard solution.
(5 um in particle diameter).
about 40.
perchloric acid (134 : 66 : 1).
time of homochlorcyclizine is about 10 minutes.
System suitability
standard solution add the mobile phase to make exactly
50 mL. Confirm that the peak area of homochlorcyclizine obtained from 10 L of this solution is equivalent to
7 to 13% of that of homochlorcyclizine obtained from 10

System performance: Dissolve 5 mg of Homochlorcyclizine Hydrochloride and 5 mg of methyl parahydroxybenzoate acid in 100 mL of the mobile phase.
under the above operating conditions, methyl parahydroxybenzoate acid and homochlorcyclizine are eluted in
this order with the resolution between these peaks being
not less than 5.
above operating conditions, the relative standard deviation of the peak area of homochlorcyclizine is not more
than 1.0%.
as the retention time of homochlorcyclizine.
hours).
Assay Weigh accurately about 0.3 g of Homochlorcyclizine Hydrochloride, previously dried, dissolve in 50 mL
of a mixture of anhydride and glacial acetic acid (7 : 3)
and titrate with 0.1 mol/L perchloric acid (potentiometric
titration, Endpoint Detdection Method in Titrimetry).
correction.

= 19.389 mg of C19H23ClN22HCl
tight containers.
Hydralazine Hydrochloride
NHNH 2
N
HCl
N
C8H8N4HCl: 196.64
Hydralazine Hydrochloride, when dried, contains not
less than 98.0% and not more than 101.0% of hydralazine hydrochloride (C8H8N4HCl).
Description Hydrazine Hydrochloride is a white, crystalline powder and is odorless and has a bitter taste.
Hydrazine Hydrochloride is soluble in water, slightly soluble in ethanol and practically insoluble in ether.
KP 9 473
solutions of Hydralazine Hydrochloride and Hydralazine
Hydrochloride RS (1 in 100000) as directed under the
(2) Determine the infrared spectra of Hydralazine
Hydrochloride and Hydralazine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Hydralazine Hydrochloride (1 in 50)
Method of Preparation Prepare as directed under Injections, with Hydralazine Hydrochloride.

Description Hydralazine Hydrochloride for Injection
is a white to pale yellow powder of mass and is odorless
and has a bitter taste.
solution of Hydralazine Hydrochloride for Injection (1 in
100000) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 238 nm and
242 nm, between 258 nm and 262 nm, between 301 nm
and 305 nm and between 313 nm and 317 nm.
pH Dissolve 1.0 g of Hydralazine Hydrochloride in 50

mL of water: the pH of the solution is between 3.5 and
4.5.
pH Dissolve 1.0 g of Hydralazine Hydrochloride for

Injection in 50 mL of water: the pH of this solution is between 3.5 and 4.5.

g of Hydralazine Hydrochloride in 50 mL of water: the
solution is clear, and colorless or pale yellow.
(2) Heavy metalsProceed with 1.0 g of Hydralazine Hydrochloride according to Method 2 and perform

P2O5, 8 hours).
Uniformity of Dosage Unit It meets the requirement

when the Mass Variation test is performed.
Assay Weigh accurately a volume (not less than 10

samples) of Hydralazine Hydrochloride for Injection,
equivalent to about 0.15 g of Hydralazine Hydrochloride,
transfer to a stoppered flask, dissolve in 25 mL of water,
add 25 mL of hydrochloric acid, cool to room temperature, add 5 mL of chloroform and titrate with 0.05 mol/L
potassium iodate VS while shaking until the purple color
of the chloroform layer disappears. The end point is
reached when the red-purple color no more reappears in
the chloroform layer within 5 minutes after the layer has
been decolorized.
Assay Weigh accurately about 0.15 g of Hydralazine

Hydrochloride, previously dried, transfer to a glassstoppered flask, dissolve in 25 mL of water, add 25 mL
of hydrochloric acid, cool to room temperature, add 5
mL of chloroform and titrate with 0.05 mol/L potassium
iodide VS while shaking until the purple color of the
chloroform layer disappears. The end point is reached
when the red-purple color no more reappears in the chloroform layer within 5 minutes after the layer has been
decolorized.
Each mL of 0.05 mol/L potassium iodate VS

= 9.832 mg of C8H8N4HCl

It

for Injection
Powder
Hydralazine Hydrochloride for Injection is a preparation

for injection which is reconstituted before use. Hydralazine Hydrochloride contains not less than 99.0% and not
more than 113.0% of the labeled amount of hydralazine
hydrochloride (C8H8N4HCl: 196.64).
Hydralazine Hydrochloride Powder contains not less

amount of hydralazine hydrochloride (C8H8N4HCl:
196.64).

Powders, with Hydralazine Hydrochloride.
Identification Weigh a portion of Hydralazine Hydrochloride Powder, equivalent to 25 mg of Hydralazine
mL of water, shake well and filter, if necessary. Add water to 2 mL of the filtrate to make 50 mL and determine
and 262 nm, between 301 nm and 305 nm and between
313 nm and 317 nm.
quirement.
It
It meets the re-
Assay Weigh accurately a portion of Hydralazine Hydrochloride Powder, equivalent to about 0.15 g of Hydralazine Hydrochloride, transfer to a glass-stoppered flask,
add 25 mL of water, shake well, add 25 L of hydrochloric acid, cool to room temperature and proceed as directed in the Assay under Hydralazine Hydrochloride.

Tablets
Hydralazine Hydrochloride Tablets contain not less than
of hydralazine hydrochloride (C8H8N4HCl: 196.64).
Method of Preparation Prepare as directed under Tablets, with Hydralazine Hydrochloride.
Identification Weigh a portion of powdered Hydralazine Hydrochloride Tablets, equivalent to 25 mg of Hydralazine Hydrochloride according to the labeled amount,
add 100 mL of water, mix well and filter, if necessary.
Take 2 mL of this solution, add water to make 50 mL and
determine the absorption spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry: it
exhibits maxima between 238 nm and 242 nm, between
258 nm and 262 nm, between 301 nm and 305 nm and
Dissolution Test Perform the test with 1 tablet of Hydralazine Hydrochloride Tablets at 50 revolutions per
using 900 mL of water. Take 30 mL or more of the dis-
solved solution after 30 minutes from the start of the

Dissolution test and filter through a membrane filter with
pore size of not more than 0.8 m. Discard the first 10
mL of the filtrate, pipet the subsequent V mL, add water
to make exactly V mL, so that each mL of the filtrate
contains about 11 g of hydralazine hydrochloride
(C8H8N4HCl) according to the labeled amount and use
this solution as the test solution. Separately, weigh accurately about 50 mg of Hydralazine Hydrochloride RS,
previously dried at 105C for 3 hours and dissolve in water to make exactly 50 mL. Pipet exactly 1 mL of this solution, add water to make exactly 100 mL and use this
solution as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard
solution, respectively at 260 nm as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Hydralazine Hydrochloride Tablets in 45 minutes should be not less than 80%.
of hydralazine hydrochloride (C8H8N4HCl)
AT
V'
1
= WS A V C 18
S
WS: Amount (mg) of Hydralazine Hydrochloride RS,
C: Labeled amount (mg) of hydralazine hydrochloride
(C8H8N4HCl) in 1 tablet.
Uniformit of Dosage Units It meets the requirement.
Assay Weigh accurately not less than 20 Hydralazine
Hydrochloride Tablets and powder. Weigh accurately a
portion of the powder, equivalent to about 0.15 g of hydralazine hydrochloride (C8H8N4HCl), transfer to a
stoppered flask and proceed as directed in the Assay under Hydralazine Hydrochloride.

= 9.832 of C8H8N4HCl
Hydrochloric Acid
HCl: 36.46
Hydrochloric Acid contains not less than 35.0% and not
more than 38.0% of hydrogen chloride (HCl).
Description Hydrochloric Acid is colorless liquid having a pungent odor.
Hydrochloric Acid is fuming but ceases to fume when it
is diluted with 2 volumes of water.
20
About 1.18.
Identification (1) Allow a glass stick wet with ammo-
KP 9 475
nia water to come near the surface of Hydrochloric Acid:
a remarkable white smoke evolves.
(2) A solution of Hydrochloric Acid (1 in 100)
changes blue litmus paper to red and responds to the Qualitative Tests for chloride.
Purity (1) SulfateTake 15 mL of Hydrochloric Acid,
add water to make 50 mL and use this solution as the test
solution. To 3 mL of the test solution, add 5 mL of water
and 5 drops of barium chloride TS and allow to stand for
1 hour: no turbidity is produced.
(2) SulfiteTake 3 mL of the test solution obtained
in (1), add 5 mL of water and 1 drop of iodine TS: the
color of iodine TS does not disappear.
(3) Bromide or iodidePlace 10 mL of the test solution obtained in (1) in a glass-stoppered test tube, add 1
mL of chloroform and 1 drop of 0.002 mol/L potassium
permanganate VS and shake well: the chloroform layer
remains colorless.
(4) Bromide or chlorinePlace 10 mL of the test solution obtained in (1) in a glass-stoppered test tube, add 5
drops of potassium iodide TS and 1 mL of chloroform
and shake for 1 minute: the chloroform layer remains
free from a purple color.
(5) Heavy metalsEvaporate 5 mL of Hydrochloric
Acid on a water-bath to dryness and add 2 mL of dilute
acetic acid and water to the residue to make 50 mL. Perform the test using this solution the test solution. Prepare
the control solution as follows: to 3.0 mL of standard
lead solution, add 2 mL of dilute acetic acid and water to
(6) MercuryDilute 20 mL of hydrochloric Acid
with water to make exactly 100 mL and use the solution
as the test solution. Perform the test with this test solution as directed under the Atomic Absorption Spectrophotometry (cold vapor type). Place the test solution in a
sample bottle of the atomic absorption spectrophotometer,
add 10 mL of stannous chloride-sulfuric acid TS, connect
the bottle immediately to the spectrophotometer, circulate air and determine the absorbance, AT, of the test solution after the recorder reading has risen rapidly and becomes constant at a wavelength of 253.7 nm. On the other hand, to 8 mL of standard mercury solution, add water
to make exactly 100 mL and determine the absorbance,
AS, of the solution obtained by the same procedure as
used for the test solution: AT is smaller than AS (not more
than 0.04 ppm).
(7) ArsenicPipet 1.7 mL of Hydrochloric Acid,
make the test solution according to Method 1 and perform the test (not more than 1 ppm).
Residue on Ignition Pipet exactly 10 mL of Hydrochloric Acid, add 2 drops of sulfuric acid, evaporate to dryness and ignite: not more than 1.0 mg of residue remains.
Assay Weigh accurately a glass-stoppered flask containing 20 mL of water, add about 3 mL of Hydrochloric
Acid and weigh accurately again. Dilute with 25 mL of
water and titrate with 1 mol/L sodium hydroxide VS (in-
dicator: 2 to 3 drops of methyl red TS).

= 36.461 mg of HCl
Dilute Hydrochloric Acid

Dilute Hydrochloric Acid contains not less than 9.5
w/v% and not more than 10.5 w/v% of hydrogen chloride (HCl: 36.46).
Description Dilute Hydrochloric Acid is a colorless
liquid. Dilute Hydrochloric Acid is odorless and has a
strong acid taste.
20
About 1.05.
Identification A solution of Dilute Hydrochloric Acid
(1 in 30) changes blue litmus paper to red and responds
to the Qualitative Tests for chloride.
Purity (1) SulfateTake 3.0 mL of Dilute Hydrochloric Acid, add 5 mL of water and 5 drops of barium
chloride TS and allow to stand for 1 hour: no turbidity is
produced.
(2) SulfiteTake 3.0 mL of Dilute Hydrochloric Acid, add 5 mL of water and 1 drop of iodine TS: the color
of iodine TS does not disappear.
(3) Bromide or iodidePlace 10 mL of Dilute Hydrochloric Acid in a glass-stoppered test tube, add 1 mL
of chloroform and 1 drop of 0.002 mol/L potassium permanganate VS and shake well: the chloroform layer remains colorless.
(4) Bromine or chlorinePlace 10 mL of Dilute
Hydrochloric Acid in a glass-stoppered test tube, add 5
drops of potassium iodide TS and 1 mL of chloroform
and shake for 1 minute: the chloroform layer remains
free from a purple color.
(5) Heavy metalsEvaporate 9.5 mL of Dilute Hydrochloric Acid in a water-bath to dryness, add 2 mL of
dilute acetic acid and water to make 50 mL and perform
the test using this solution as the test solution. Prepare
the control solution as follows: to 3.0 mL of standard
lead solution, add 2 mL of dilute acetic acid and water to
(6) MercuryDilute 80 mL of Dilute Hydrochloric
Acid with water to make exactly 100 mL and use this solution as the test solution. Perform the test with this solution according to the Atomic Absorption Spectrophotometry (cold vapor type). Place the test solution in a sample bottle of the atomic absorption spectrophotometer,
add 10 mL of stannous chloride-sulfuric acid TS, connect
the bottle immediately to the spectrophotometer, circulate air and read the absorbance, AT , of the test solution
after the recorder reading has risen rapidly and become

constant at a wavelength of 253.7 nm. Separately, to 8
mL of standard mercury solution, add water to make exactly 100 mL and read the absorbance, AS , of the solution obtained by the same procedure as used for the test
solution: AT is smaller than AS (not more than 0.01
ppm).
(7) ArsenicProceed with 4.0 mL of Dilute Hydrochloric Acid according to Method 1 and perform the
Residue on Ignition Pipet exactly 10 mL of Dilute
Hydrochloric Acid, add 2 drops of sulfuric acid, evaporate to dryness and ignite: the weight of the residue is not
more than 1.0 mg.
Assay Measure exactly 10 mL of Dilute Hydrochloric
Acid and dilute with 20 mL of water. Titrate with 1
mol/L sodium hydroxide VS (indicator: 2 to 3 drops of
methyl red TS).

= 36.461 mg of HCl
Hydrochlorothiazide
O
O
S
H2N
S
O
Cl
NH
N
H
C7H8CIN3O4S2: 297.74
Hydrochlorothiazide, when dried, contains not less than
99.0% and not more than 101.0% of hydrochlorothiazide
(C7H8CIN3O4S2).
Description Hydrochlorothiazide is a white crystal or
taste.
Hydrochlorothiazide is freely soluble in acetone, sparingly soluble in methanol, very slightly soluble in water or
Hydrochlorothiazide dissolves in sodium hydroxide TS.
Identification (1) Take 5 mg of Hydrochlorothiazide,
add 5 mL of chromotropic acid TS and allow to stand for
5 minutes: a purple color is observed.
(2) Fuse a mixture of 0.1 g of Hydrochlorothiazide
and 0.5 g of sodium carbonate cautiously: the gas
evolved changes moistened red litmus paper to blue. After cooling, crush with a glass rod, add 10 mL of water,
stir and filter. Take 4 mL of the filtrate, add 2 drops of
hydrogen peroxide (28) solution, 5 mL of diluted hydrochloric acid (1 in 5) and 2 to 3 drops of barium chlo-
ride TS: a white precipitate is produced,

(3) Take 4 mL of the filtrate obtained in (2), add 5
mL of dilute nitric acid and 3 drops of silver nitrate TS: a
white precipitate is produced.
(4) Dissolve 12 mg each of Hydrochlorothiazide and
Hydrochlorothiazide RS in 100 mL of sodium hydroxide
TS. To 10 mL each of these solutions, add water to make
100 mL and determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
Purity (1) ChlorideDissolve 1.0 g of Hydrochlorothiazide in 30 mL of acetone, add 6 mL of dilute nitric
this solution as the test solution. Prepare the control solution as follows: to 1.0 mL of 0.01 mol/L hydrochloric acid VS, add 30 mL of acetone, 6 mL of dilute nitric acid
and water to make 50 mL (not more than 0.036%).
(2) SulfateDissolve 1.0 g of Hydrochlorothiazide
in 30 mL of acetone, add 1 mL of dilute hydrochloric acid and water to make 50 mL and perform the test using
VS, add 30 mL of acetone, 1 mL of dilute hydrochloric
(3) Heavy metalsProceed with 1.0 g of Hydrochlorothiazide according to Method 2 and perform the test.
Prepare the test solution with 2.0 mL of standard lead solution (not more than 20 ppm).
(4) Primary aromatic aminesDissolve 80 mg of
Hydrochlorothiazide in acetone to make exactly 100 mL.
Measure exactly 1 mL of the solution, add 3.0 mL of dilute hydrochloric acid, 3.0 mL of water and 0.15 mL of
sodium nitrite TS, shake and allow to stand for 1 minute.
Shake this solution with 1.0 mL of ammonium sulfamate
TS, allow to stand for 3 minutes, then add 1.0 mL of N(l-naphthyl)-N-diethylethylenediamine oxalate TS, shake
and allow to stand for 5 minutes. Perform the test with
this solution as directed under the Ultraviolet-visible
Spectrophotometry, using a solution prepared with 1.0
mL of acetone in the same manner as the blank: the absorbance at 525 nm is not more than 0.10.
hours).
Assay Weigh accurately about 30 mg each of Hydrochlorothiazide and hydrochlorothiazide RS, previously
dried and dissolve in 150 mL of the mobile phase, add
add the mobile phase to make 200 mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L each of the test
Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS, of the peak
KP 9 477
area of Hydrochlorothiazide to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of hydrochlorothiazide (C7H8CIN3O4S2)
QT
= amount (mg) of Hydrochlorothiazide RS Q
S
Internal standard solutionA solution of 8aminoacetophenone in acetonitrile (9 in 2000).
about 25 C.
Mobile phase: pH 3.0, a mixture of 0.1 mol/L monobasic sodium phosphate TS and acetonitrile (9 : 1).
time of Hydrochlorothiazide is about 10 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, hydrochlorothiazide and the internal
standard are eluted in this order with a resolution between their peaks being not less than 4.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of hydrochlorothiazide
to that of the internal standard is not more than 1.0%.
Hydrocortisone
O
H3C
H
HO
CH2OH
OH
H3C
Hydrocortisone is sparingly soluble in methanol, in ethanol and in dioxane, slightly soluble in chloroform and
very slightly soluble in ether and in water.
Melting pointBetween 212 C and 220 C (with decomposition).
Identification (1) Take 2 mg of Hydrocortisone, add 2
mL of sulfuric acid: the solution shows a yellow-green
fluorescence immediately and the color of the solution
changes gradually from orange to dark red. Dilute carefully the solution with 10 mL of water: the color changes
through yellow to orange-yellow with green fluorescence
and a small amount of a flocculent precipitate is produced.
(2) Dissolve 10 mg of Hydrocortisone in 1 mL of methanol, add 1 mL of Fehling's TS and heat: a red precipitate is produced.
(3) Determine the infrared absorption spectra of Hydrocortisone and Hydrocortisone RS, previously dried, as
difference appears, dissolve the test and RS in ethanol,
respectively, evaporate to dryness and repeat the test on
the residues.
Purity Related substancesDissolve 20 mg of Hydrocortisone in 10 mL of a mixture of chloroform and
methanol (9 : 1) and use this solution as the test solution.
Pipet exactly 1 mL of this solution, add a mixture of
chloroform and methanol (9 : 1) to make exactly 50 mL
directed under the Thin-layer chromatography. Spot 10
a plate of silica gel with fluorescent indicator for Thinlayer chromatography. Develop the plate with a mixture
of chloroform and ethanol (17 : 3) to a distance of about
hours).
C21H30O5: 362.47
Hydrocortisone, when dried, contains not less than
97.0% and not more than 102.0% of hydrocortisone
(C21H30O5).
Description Hydrocortisone is a white, crystalline
Assay Dissolve about 20 mg each of Hydrocortisone

and Hydrocortisone RS, previously dried and accurately
weighed, in 20 mL each of a mixture of chloroform and
methanol (9 : 1), add 10 mL each of the internal standard
solution, then add a mixture of chloroform and methanol
(9 : 1) to make 50 mL and use these solutions as the test
solution and the standard solution, respectively. Perform
the test with 5 L each of the test solution and the stan-

dard solution as directed under the Liquid Chromatography according to the following conditions and calculate
the ratios, QT and QS, of the peak area of Hydrocortisone
Amount (mg) of hydrocortisone (C21H30O5)
QT
= amount (mg) of Hydrocortisone RS Q
S
Internal standard solutionA solution of prednisone
in a mixture of chloroform and methanol (9 : 1) (9 in
10000).
about 20 C.
Mobile phase: A mixture of chloroform, methanol
and anhydrous acetic acid (1000 : 20 : 1).
time of Hydrocortisone is about 15 minutes.
System suitability
above operating conditions, the internal standard and hydrocortisone are eluted in this order with a resolution between their peaks being not less than 7.
deviation of the ratios of the peak area of hydrocortisone
to that of the internal standard is not more than 1.0.
Hydrocortisone Tablets
Hydrocortisone Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of hydrocortisone (C21H30O5: 362.46).
Method of Preparation Prepare as directed under Tablets, with Hydrocortisone.
Identification Weigh a portion of powdered Hydrocortisone Tablets, equivalent to about 50 mg of Hydrocortisone according to the labeled amount, add 15 mL of hexane, shake for 15 minutes and remove the hexane. Take
the residue, add 10 mL of hexane again, shake for 15 minutes, remove the hexane, add 10 mL of peroxide-free
ether, shake for 15 minutes, remove the ether, add 25 mL
of anhydrous ethanol, shake for 15 minutes, filter and

evaporate the filtrate in a water-bath to dryness. Proceed
with the residue as directed in the Identification (3) under
Hydrocortisone.
Dissolution Test Perform the test with 1 tablet of Hydrocortisone Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of water. Take the dissolved solution after 30 minutes
from starting of the test, filter, dilute with the dissolution
medium, if necessary and use this solution as the test solution. Separately, weigh accurately a portion of Hydrocortisone RS, dried at 105 C for 3 hours, add the dissolution medium to make the same concentration as the test
standard solution at 248 nm as directed under the Ultraviolet-visible Spectrophotometry using the test solution
as the blank.
The dissolution rate of Hydrocortisone Tablets in 30 minutes is not less than 70%.
to the following procedure. Transfer 1 tablet of Hydrocortisone Tablets to a suitable container and add about
0.3 mL of water directly on the tablet. Allow the tablet to
stand for about 5 minutes. Shake the container to break
up the tablet and sonicate to ensure complete disintegration. Add 4 to 5 small glass beads and 50.0 mL of the internal standard solution to the container. Shake the container for about 30 minutes. Dilute a V mL of the clear
supernatant liquid, accurately measured, with a known,
accurately measured volume of the internal standard solution to obtain a solution having a known concentration
of 0.1 mg per mL and use this solution as the test solution. Separately, weigh accurately a portion of Hydrocortisone RS, previously dried at 105 C for 3 hours, dissolve in the internal standard solution to obtain a solution
having a known concentration of 0.1 mg per mL and use
with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS, of the peak area of Hydrocortisone to
that of the internal standard for the test solution and the

V'
QT
= 50 V C Q
S
V: Final volume (mL) of the test solution,
C: Concentration (mg/mL) of standard solution.
Internal standard solutionA solution of prednisone
in a saturated chloroform in water (6 in 100000).
KP 9 479
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, having porous
silica gel for liquid chromatography (3 m to 10 m in
particle diameter).
Mobile phase: A mixture of butyl chloride, a saturated butyl chloride in water, tetrahydrofuran, methanol
and anhydrous acetic acid (95 : 95 : 4 : 7 : 6).
System suitability
above operating conditions, the resolution between their
times, as directed under the above conditions, the relative
standard deviation of the ratios of the peak area is not
more than 2.0%.
Hydrocortisone Tablets, weigh accurately a portion of the
powder, equivalent to about 5 mg of hydrocortisone
(C21H30O5), transfer to a centrifuge and add 50 mL of the
internal standard solution. Shake vigorously for 30 minutes, centrifuge and use the clear supernatant liquid as
the test solution. Proceed as directed in the Uniformity of
Dosage Units under Hydrocortisone

QT
= 50 C Q
S
Hydrocortisone Acetate
O
O
H
H3C
HO
CH2O
OH
CH3
H3C
C23H32O6: 404.50
Hydrocortisone Acetate, when dried, contains not less
than 97.0% and not more than 102.0% of hydrocortisone
acetate (C23H32O6).
Description Hydrocortisone Acetate is a white crystals
Hydrocortisone Acetate is sparingly soluble in dioxane,
slightly soluble in methanol, in ethanol or in chloroform,
very slightly soluble in ether and practically insoluble in
water.
Hydrocortisone Acetate: the solution shows a yellowish
green fluorescence immediately and the color of the solution gradually changes through orange-yellow to dark
red. This solution shows a strong light green fluorescence under ultraviolet light. Add carefully 10 mL of water to this solution: the color changes from yellow to
orange-yellow with a light green fluorescence and a yellow-brown, flocculent precipitate is formed.
(2) Dissolve 10 mg of Hydrocortisone Acetate in 1
mL of methanol by warming, add 1 mL of Fehling's TS
and heat: an orange to red precipitate is formed.
(3) Take 50 mg of Hydrocortisone Acetate, add 2 mL
of potassium hydroxide-ethanol TS and heat in a waterbath for 5 minutes. Cool, add 2 mL of diluted sulfuric acid (2 in 7) and boil gently for 1 minute: the odor of ethyl
acetate is perceptible.
(4) Determine the infrared spectra of Hydrocortisone
Acetate and Hydrocortisone Acetate RS, previously dried,
similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve the test sample
and RS in ethanol, respectively, evaporate to dryness and
repeat the test on the residues.
+ 165 (after drying, 50 mg, dioxane, 10 mL, 100 mm).
Purity Related substancesDissolve 0.040 g of Hydrocortisone Acetate in 25 mL of a mixture of chloroform and methanol (9 : 1) and use this solution as the test
solution. Pipet exactly 2 mL of the test solution, add a
mixture of chloroform and methanol (9 : 1) to make exactly 100 mL and use this solution as the standard solution. Perform the test with the test solution and the standard solutions as directed under the Thin-layer chromatography. Spot 5 L each of the test solution and the
standard solution on a plate of silica gel for Thin-layer
dichloromethane, ether, methanol and water (160 : 30 :
Spray evenly alkaline blue tetrazolium TS on the plate:
solution.
hours).
Assay Dissolve about 20 mg each of Hydrocortisone
Acetate and Hydrocortisone acetate RS, previously dried
and accurately weighed, in methanol, add exactly 10 mL

each of the internal standard solution, then add methanol
according to the following operating conditions and calculate the ratios, QT and QS, of the peak area of Hydrocortisone Acetate to that of the internal standard, for the
Amount (mg) of hydrocortisone acetate (C23H32O6)
QT
= amount (mg) of Hydrocortisone Acetate RS Q
S
(Aqueous Suspension) shows a white turbidity on shaking.

Identification Shake well and transfer a volume of
Hydrocortisone Acetate Injection (Aqueous Suspension),
equivalent to 50 mg of Hydrocortisone Acetate according
to the labeled amount, to a separator. Extract with two 10
mL volumes of ether, remove the ether extracts, filter by
suction, wash the filter with small amount of water, dry
at 105 C for 1 hour and proceed with the residue as directed in the Identification (4) under Hydrocortisone
Acetate.
pH
Internal standard solutionA solution of benzyl phydroxybenzoate in methanol (1 in 1000).

(13 : 7).
time of Hydrocortisone Acetate is about 8 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions, hydrocortisone acetate and the internal standard are eluted in this order with a resolution between their peaks being not less than 4.
above operating conditions, the relative standard deviation of the ratios of the peak area of hydrocortisone acetate to that of the internal standard is not more than l.0%.
Packing and storage Preserve in tight containers.
Hydrocortisone Acetate Injection

Hydrocortisone Acetate Injection (Aqueous Suspension)
is an aqueous suspension for injection. Hydrocortisone
Acetate Injection contains not less than 90% and not
more than 110% of the labeled amount of hydrocortisone
acetate (C23H32O6: 404.50).
Method of Preparation Prepare as directed under Injections, with Hydrocortisone Acetate.
Description
Hydrocortisone
Acetate
Injection
Between 5.0 and 7.0

Assay Shake well, measure exactly a volume of Hydrocortisone Acetate Injection (Aqueous Suspension),
equivalent to about 50 mg of hydrocortisone acetate
(C23H32O6) in separatory funnel, add 15 mL of water,
four 25 mL volumes of chloroform. Filter each extracts
with absorbent cotton, previously moistened with chloroform, add chloroform to make exactly 100 mL. Pipet exactly 10 mL to 50-mL glass stopper flask, dry in water
bath, and cool. Dissolve the residue in 20.0 mL of ethanol and use this solution as the test solution. Separately,
weigh accurately about 50 mg of Hydrocortisone Acetate
RS, dissolve in ethanol to make exactly 250 mL. Pipet
exactly 5 mL of this solution, add ethanol to make exactly 100 mL and use this solution as the standard solution.
Take 2 flasks each with the test solution and the standard
solution and a flask with 20.0 mL of ethanol for blank
test, add a 2.0 mL solution of 50 mg of bluetetrazol in 20
mL of methanol and mix. Add 2.0 mL of ethanoltetramethylammoniumhydroxide (9 : 1) to each flask and
mix. Place them in dark place for 90 minutes. Perform
directed under the Ultraviolet-visible Spectrophotometry
at the 525 nm and measure the absorbance, AT and AS,
for the test solution and the standard solution, respectively, using the blank solution as a blank.
Amount (mg) of hydrocortisone acetate (C23H32O6)

AT
= amount (mg) of Hydrocortisone Acetate RS A
S
KP 9 481
Hydrocortisone Butyrate
O
H
H3C
CH2OH
C
HO
O
H3C
CH2CH2CH3
C25H36O6: 432.55
Hydrocortisone Butyrate, when dried, contains not less
butyrate (C25H36O6).
Description Hydrocortisone Butyrate is a white powder and is odorless.
Hydrocortisone Butyrate is freely soluble in tetrahydrofuran, in chloroform or in 1,2-dichlroethane, soluble in
methanol, sparingly soluble in dehydrated ethanol,
Hydrocortisone Butyrate: the solution shows a yellowish
green fluorescence immediately and the color of the solution gradually changes through orange-yellow to dark
red. This solution shows a strong light green fluorescence under ultraviolet light (main wavelength: 254 nm).
Add carefully 10 mL of water to this solution: the color
changes from yellow to orange-yellow with a light green
fluorescence and a yellow-brown, flocculent precipitate
is produced.
(2) Dissolve 10 mg of Hydrocortisone Butyrate in 1
mL of methanol by warming, add 1 mL of Fehlings TS
and heat: an orange to red precipitate is formed.
(3) Take 50 mg of Hydrocortisone Butyrate, add 2
mL of potassium hydroxide-ethanol TS and heat on a water-bath for 5 minutes. Cool, add 2 mL of diluted sulfuric
acid (2 in 7) and boil gently for 1 minute: the odor of
ethyl butyrate is perceptible.
(4) Determine the infrared absorption spectra of Hydrocortisone Butyrate and Hydrocortisone Butyrate RS,
same wavenumbers
D : Between +48 and
+52 (after drying, 0.1 g, chloroform, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Hydrocortisone Butyrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
(2) Related substancesDissolve 25 mg of Hydrocortisone Butyrate in 5 mL of tetrahydrofuran and use

this solution and add tetrahydrofuran to make exactly 50
mL. Pipet exactly 5 mL of this solution, add tetrahydrofuran to make exactly 20 mL and use this solution as the
the standard solution on a plate of silica gel for thin-layer
1,2-dichloroethane, methanol and water (470 : 30 : 1) to
evenly alkaline blue tetrazolium TS on the plate: the
are not more than two in number and not more intense
than those from the standard solution in color.
hours).
Assay Weigh accurately about 50 mg of Hydrocortisone Butyrate, previously dried and dissolve in dehydrated ethanol to make exactly 100 mL. Pipet exactly 2
mL of this solution and add dehydrated ethanol to make
exactly 50 mL. Determine the absorbance, A, of this solution at the wavelength of a maximum absorption at
Spectrophotometry.
Amount (mg) of hydrocortisone butyrate (C25H36O6)

A
= 375 25000
Hydrocortisone Sodium
Phosphate
O
H3C
CH2OPO 3Na2
OH
HO
H
H3C
C21H29Na2O8P: 486.40
Hydrocortisone Sodium Phosphate contains not less than
96.0% and not more than 102.0% of Hydrocortisone sodium phosphate (C21H29Na2O8P), calculated on the dried
basis.
Description Hydrocortisone Sodium Phosphate is a
white to pale yellow powder and is odorless.

Hydrocortisone Sodium phosphate is freely soluble in
water, sparingly soluble in methanol, very slightly soluble in ethanol and practically insoluble in ether.
Hydrocortisone Sodium Phosphate is hygroscopic.
Identification (1) Take 2 mg of Hydrocortisone Sodium Phosphate, add 2 mL of sulfuric acid: a yellowish
green fluorescence is exhibited initially, then gradually
changes through orange-yellow to dark red. Examine the
solution under ultraviolet light (main wavelength: 254
nm): an intense, light green fluorescence is exhibited.
Take this solution, add carefully 10 mL of water: the color changes from yellow to orange-yellow with a light
green fluorescence and a yellow-brown, flocculent floating substance is formed.
(2) Determine the infrared absorption spectra of Hydrocortisone Sodium Phosphate and Hydrocortisone Sodium Phosphate RS as directed in the paste method under
similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve each of Hydrocortisone Sodium Phosphate and Hydrocortisone Sodium
Phosphate RS in methanol, evaporate to dryness and repeat the test on the residues.
(3) Moisten 1.0 g of Hydrocortisone Sodium Phosphate with a small volume of sulfuric acid and incinerate
by gradual heating. After cooling, dissolve the residue in
10 mL of dilute nitric acid and heat in a water-bath for 30
minutes. After cooling, filter, if necessary: this solution
responds to the Qualitative Tests for sodium salt and for
phosphate.
+ 129 (1 g, calculated on the dried basis, phosphate buffer solution, pH 7.0, 100 mL, 100 mm).
pH Dissolve 1.0 g of Hydrocortisone Sodium Phosphate in 100 mL of water: the pH of this solution is between 7.5 and 9.5.
g of Hydrocortisone Sodium Phosphate in 10 mL of water: the solution is clear and colorless to pale yellow.
(2) ChlorideDissolve 0.30 g of Hydrocortisone
Sodium Phosphate in 20 mL of water and add 6 mL of
dilute nitric acid and water to make 100 mL. To 5 mL of
this solution, add water to make 50 mL. Perform the test
using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric
acid VS (not more than 0.600%).
(3) Heavy metalsProceed with 0.5 g of Hydrocortisone Sodium Phosphate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of
Hydrocortisone Sodium Phosphate according to Method
3 and perform the test (not more than 2 ppm).
0.25 g of Hydrocortisone Sodium Phosphate, dissolve in
water to make exactly 100 mL and use this solution as

the test solution. Pipet exactly 5 mL each of the test solution and phosphoric acid solution VS into separate volumetric flasks, add 2.5 mL of ammonium molybdatesulfuric acid TS and 1 mL of 1-amino-2-naphthol-4sulfonic acid TS, shake, add water to make exactly 25
mL and allow to stand at 20 1C for 30 minutes. Perform the test with the test solution and the standard solutions as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared with 5 mL of water in the same manner as a blank. Determine the absorbances, AT and AS, of the test solution and the standard
solution, respectively, at 740 nm: the amount of free
phosphoric acid is not more than 1.0%.
Content (%) of free phosphoric acid (H3PO4)
1
AT
= A W 257.8
S
W: Amount (mg) of Hydrocortisone Sodium Phosphate, calculated on the dried basis.
(6) Free hydrocortisoneDissolve 25 mg of Hydrocortisone Sodium Phosphate in the mobile phase to make
Separately, weigh 25 mg of Hydrocortisone RS, previously dried at 105 C for 3 hours and dissolve in the
mobile phase to make exactly 100 mL. Pipet exactly 10
mL of this solution, add the mobile phase to make exactly 200 mL and use this solution as the standard solution.
the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the peak areas, AT and As, of hydrocortisone
from each solution: AT is not larger than AS.
Proceed as directed under the operating conditions in
the Assay.
System suitability
System performance: Proceed as directed under
the system performance in the Assay.
above operating conditions, the relative standard deviation of the peak area of hydrocortisone is not more than
1.0%.
80 C, 5 hours).
Assay Weigh accurately about 20 mg each of Hydrocortisone Sodium Phosphate and Hydrocortisone Sodium
Phosphate RS (determine its loss on drying before use),
dissolve each in 50 mL of the mobile phase, add exactly
10 mL of the internal standard solution, then add the mobile phase to make 200 mL and use these solutions as the
KP 9 483
standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS, of the peak area of hydrocortisone phosphate to that of the internal standard, for
Amount (mg) of hydrocortisone sodium
phosphate (C21H29Na2O8P) = amount (mg) of
Hydrocortisone Sodium Phosphate RS,
QT
calculated on the dried basis Q
S
Internal standard solutionA solution of isopropyl
parahydroxybenzoate in the mobile phase (3 in 5000).
about 25 C.
Mobile phase: A mixture of 0.05 mol/L sodium dihydrogen phosphate TS, pH 2.6 and methanol (1 : 1).
time of hydrocortisone phosphate is about 10 minutes.
System suitability
with 20 L of the standard solution under the above operating conditions and calculate the resolution, hydrocortisone phosphate and isopropyl parahydroxybenzoate are
rimes with 20 L of the standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak area of hydrocortisone
phosphate to thai of the internal standard is not more
than 1.0%.
Hydrocortisone Sodium
Succinate
O
H3C
H
HO
O
CH2O
CH2CH2CO2Na
OH
H3C
Description Hydrocortisone Sodium Succinate is a

white powder or mass and is odorless.
Hydrocortisone Sodium Succinate is freely soluble in
water, in methanol or in ethanol and practically insoluble
in ether.
Hydrocortisone Sodium Succinate is hygroscopic.
Hydrocortisone Sodium Succinate is gradually colored
by light.
Identification (1) Dissolve 0.2 g of Hydrocortisone
Sodium Succinate in 20 mL of water. and add 0.5 mL of
dilute hydrochloric acid with stirring: a white precipitate
is formed. Collect the precipitate. wash it with two 10mL portions of water, and dry at 105 C for 3 hours. To 3
mg of this dried matter add 2 mL of sulfuric acid: the solution shows a yellowish green fluorescence immediately,
and the color of the solution gradually changes through
orange-yellow to dark red. This solution shows a strong
light green fluorescence under ultraviolet light. Add carefully 10 ml of water to this solution: the color changes
from yellow to orange-yellow with a light green fluorescence, and a yellow-brown flocculent precipitate is
formed.
(2) Dissolve 10 mg of the dried matter obtained in (1)
in 1 mL of methanol, add 1 mL of Fehling's TS, and heat:
an orange to red precipitate is formed.
(3) To 0.1 g of the dried matter obtained in (1) add 2
mL of sodium hydroxide TS, and allow to stand for 10
minutes. Filter the solution to remove the precipitate
formed, mix the filtrate with 1 mL of dilute hydrochloric
acid, filter if necessary, then adjust the solution to a pH
of about 6 with diluted ammonia TS (1 in 10), and add 2
to 3 drops of iron (III) chloride TS: a brown precipitate is
formed.
(4) Determine the infrared absorption spectra of the
dried matter obtained in (1) and Hydrocortisone Sodium
Succinate RS as directed in the potassium bromide disk
method under Infrared Spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavenumbers. If any difference appears between the specera, dissolve Hydrocortisone Sodium Succinate and Hydrocortisone Sodium Succinate RS in methanol, respectively, then evaporate the methanol to dryness, and repeal
the test on the residues.
(5) Hydrocortisone Sodium Succinate responds to the
Qualitative Tests (1) for sodium salt.
+145 (0.1 g, calculated on the dried basis, ethanol, 10
mL, 100 mm).
Hydrocortisone Sodium Succinate contains not less than

97.0% and not more than 103.0% of hydrocortisone sodium succinate (C25H33NaO8), calculated on the dried basis.
C25H33NaO8: 484.51

g of Hydrocortisone Sodium Succinate in 10 mL of water: the solution is clear and colorless.

(2) Related substancesDissolve 25 mg of Hydrocortisone Sodium Succinate in methanol to make exactly
10 mL and use this solution as the test solution. Separately, dissolve 25 mg of hydrocortisone RS in methanol to
make exactly 10 mL. Pipet exactly 1 mL of this solution,
add methanol to make exactly 20 mL and use this solution as the standard solution (1). Pipet exactly 6 mL of
the standard solution (1), add methanol to make exactly
solutions (1) and (2) as directed under the Thin-layer
the standard solutions (1) and (2) on a plate of silica gel
Develop the plate with a mixture of chloroform, dehydrated ethanol and formic acid (150 : 10 : 1) to a distance
of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot from
the test solution corresponding to the spot from the standard solution (1) is not more intense than the spot from
the standard solution (1). Any spot other than the principal spot and the above spot obtained from the test solution is not more than one and is not more intense than the
spot from the standard solution (2).
hours).
Assay Weigh accurately about 10 mg of Hydrocortisone Sodium Succinate and dissolve in methanol to make
methanol to make exactly 50 mL and use this solution as
mg of Hydrocortisone Succinate RS, previously dried at
105 C for 3 hours, proceed in the same manner as directed for the test solution and use this solution as the
standard solution. Determine the absorbances, AT and AS,
Amount (mg) of hydrocortisone sodium succinate

(C25H33NaO8) = amount (mg) of Hydrocortisone
AT
Sodium Succinate RS A 1.0475
S
tight containers.
Hydrocortisone Succinate
O
H3C
H
HO
O
CH2O
CH2CH2CO 2H
OH
H
H3C
C25H34O8: 462.53
Hydrocortisone Succinate, when dried, contains not less
succinate (C25H34O8.)
Description Hydrocortisone Succinate is a white, crystalline powder and is odorless.
Hydrocortisone Succinate is very soluble in methanol,
freely soluble in dehydrated ethanol, sparingly soluble in
ethanol, very slightly soluble in ether and practically insoluble in water.
Identification (1) Take 3 mg of Hydrocortisone Succinate, add 2 mL of sulfuric acid: the solution shows a yellowish green fluorescence immediately and the color of
the solution gradually changes through orange-yellow to
dark red. This solution shows a strong light green fluorescence under ultraviolet light. Add carefully 10 mL of
water to this solution: the color changes from yellow to
orange-yellow with a light green fluorescence and a yellow-brown flocculent precipitate is produced.
(2) Determine the infrared absorption spectra of Hydrocortisone Succinate and Hydrocortisone Succinate RS,
previously dried, according to the potassium bromide
same wavenumbers. If any difference appears, dissolve
Hydrocortisone Succinate and Hydrocortisone Succinate
RS in methanol, respectively, evaporate to dryness and
perform the test on the residues.
+153 (after drying, 0.1 g, dehydrated ethanol, 10 mL,
100 mm).
g of Hydrocortisone Succinate in 10 mL of methanol: the
(2) Related substancesDissolve 25 mg of Hydrocortisone Succinate in methanol to make exactly 10 mL
and use this solution as the test solution. Separately, dissolve 25 mg of Hydrocortisone RS in methanol to make
methanol to make exactly 50 mL and use this solution as
and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Devel-
KP 9 485
op the plate with a mixture of chloroform, dehydrated
ethanol and formic acid (150 : 10 : 1) to a distance of
hours).

tight containers.
Hydrogen Peroxide Solution

Assay Weigh accurately about 50 mg each of Hydrocortisone Succinate and Hydrocortisone Succinate RS,
previously dried and dissolve in methanol to make exactly 50 mL. Pipet exactly 5 mL each of these solutions, add
add methanol to make 50 mL and use these solutions as
the standard solution as directed under the Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS, of the peak area
of hydrocortisone succinate to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of hydrocortisone succinate (C25H34O8)

QT
= amount (mg) of Hydrocortisone Succinate RS Q
S
Internal standard solutionA solution of butyl parahydroxy benzoate in methanol (1 in 2500).
Column: A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with octadecylsilanized silica gel (5 m to 10 m in particle diameter).
about 25 C.
Mobile phase: A mixture of acetic acid-sodium acetate buffer solution, pH 4.0 and acetonitrile (3 : 2).
time of hydrocortisone succinate is about 5 minutes.
System suitability
above operating conditions, hydrocortisone succinate and
the internal standard in this order with the resolution between their peaks being not less than 9.
under the above operating conditions, the relative deviation of the peak area of hydrocortisone succinate is not
more than 1.0%.
Hydrogen Peroxide Solution contains not less than 2.5%

and not more than 3.5% of hydrogen peroxide (H2O2:
34.02).
Hydrogen Peroxide Solution contains not more than 0.5
w/v% of suitable preservatives.
Description Hydrogen Peroxide Solution is a colorless,
clear liquid and is odorless or has ozone-like odor.
Hydrogen Peroxide Solution is acidic and produce bubbles in the opening of the container.
Hydrogen Peroxide Solutions decomposition is accelerated by contacting oxidants or reductants.
Hydrogen Peroxide Solution can be degraded by heat.
Hydrogen Peroxide Solution needs to be protected from
light.
20
About 1.01.
Identification Shake 1 mL of Hydrogen Peroxide Solution with 10 mL of water containing 1 drop of dilute
sulfuric acid, and add 2 mL of ether. Subsequently, 1
drop of potassium chromate TS is added to produce an
evanescent blue color in water layer which, upon agitation and standing, passes into the ether layer.
Purity (1) AcidityTake 25 mL of Hydrogen Peroxide
Solution, add 2 drops of phenolphthalein and 2.5 mL of
0.1 mol/L sodium hydroxide: a red color develops.
(2) Heavy metalsTake 5 mL of Hydrogen Peroxide
Solution, add 20 mL of water and 2 mL of Ammonia TS
and evaporate on a water-bath to dryness. Dissolve the
residue in 2 mL of dilute acetic acid by heating and add
as a test solution. Pipet 2.5 mL of standard lead solution
and add 2 mL of dilute acetic acid and water to make 50
mL and use this solution as a reference solution (not
more than 5 ppm).
(3) BariumTo 1.0 mL add two drops of 2 N sulfuric acid: no turbidity or precipitate is produced within 10
minutes.
(4) Organic preservativesPipet 100.0 mL of Hydrogen Peroxide Solution and extract sequentially with
50 mL, 25 mL and 25 mL volumes of a mixture of chloroform and ether (3 : 2), place the combined extracts in
the container, previously weighed, evaporate at room
temperature and dry the residue in a desiccator with silica gel for 2 hours: not more than 50 mg.
(5) Non volatile residuePipet 2.0 mL of Hydrogen

Peroxide Solution, evaporate on a water-bath to dryness
and dry residue at 105 o C for 1 hour: not more than 30
mg.
Assay Place accurately about 2 mL of Hydrogen Peroxide Solution to a flask containing 20 mL of water, add
20 mL of dilute sulfuric acid and titrate with 0.02 mol/L
potassium permanganate VS.
Each mL of 0.02 mol/L potassium permanganate VS

= 1.701 mg of H2O2
tight containers. Store at 30 C or less.
Hydroxocobalamin Acetate
O
H2N
H2N
C
C
CH2CH2
H2N
H3C
CH2
N
H3C
H2C
NH2
CH3
H CH2CH2
H3C
O
C
NH2
CH3CO2H
CH2CH2
O
O
CH2CH2
CH3
H2C
NH2
Co
H3C
C
OH
N
NH
CH2
H
O CH3
O
CH3
CH3
CH3
OH
C
H
CH3 O
H
H
H
O
CH2OH
C62H89CoNl3O15PC2H4O2: 1406.41
Hydroxocobalamin Acetate contains not less than 95.0%
and not more than 101.0% of hydroxocobalamin acetate
(C62H89CoNl3O15P C2H4O2), calculated on the dried basis.
Description Hydroxocobalamin Acetate is a dark red
crystal or powder and is odorless.
Hydroxocobalamin Acetate is freely soluble in water,
ether.
Hydroxocobalamin Acetate is hygroscopic.
solutions of Hydroxocobalamin Acetate and Hydroxocobalamin Acetate RS in acetic acid-sodium acetate buffer
solution, pH 4.5, (1 in 50000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Mix 1 mg of Hydroxocobalamin Acetate with 50
mg of potassium hydrogen sulfate, and fuse by igniting.

Cool, break up the mass with a glass rod, add 3 mL of
water, and dissolve by boiling. Add 1 drop of phenolphthalein TS, and add dropwise sodium hydroxide TS until
the solution devellops a light red. Then add 0.5 g of sodium acetate trihydrate, 0.5 mL of dilute acetic acid and
0.5 mL of a solution of disodium l-nitroso-2-naphthol3,6-disulfonate (1 in 500): a red to orange-red color develops immediately. Then add 0.5 mL of hydrochloric
acid, and boil for 1 minute: the red color does not disappear.
(3) Add 0.5 mL of dehydrated ethanol and 1 mL of
sulfuric acid to 20 mg of Hydroxocobalamin Acetate and
heat the mixture: the odor of ethyl acetate is perceptible.
Purity Cyanocobalamin and colored related substancesDissolve 50 mg of Hydroxocobalamin Acetate
in exactly 5 mL each of acetic acid-sodium acetate buffer
solution, pH 5.0, in two tubes. Take one tube, add 0.15
mL of potassium thiocyanate TS, allow to stand for 30
minutes and use this solution as the test solution (1). To
the other tube, add 0.10 mL of potassium cyanide TS, allow to stand for 30 minutes and use this solution as the
test solution (2). Separately, dissolve 3.0 mg of Cyanocobalamin RS in exactly 10 mL of acetic acid-sodium
acetate buffer solution, pH 5.0 and use this solution as
the standard solution. Perform the test with the test solutions (1) and (2) and the standard solution as directed
under the Thin-layer chromatography. Apply 20 L each
of the test solutions (1) and (2) and the standard solution,
25 mm in length along the starting line, 10 mm apart
from each other, on a plate of silica gel for thin-layer
chromatography. Develop the plate for 18 hours with 2butanol saturated with water, while supporting the plate
at an angle of about 15 to a horizontal plane and air-dry
the plate: the spot from the test solution (1) corresponding to that from the standard solution is not more intense
than the spot from the standard solution and the spots
other than the principal spot from the test solution (2) are
Loss on Drying Not more than 12% (0.05 g, in vacuum, at a pressure not exceeding 0.67 kPa, P2O5, l00 C,
6 hours).
Assay Weigh accurately about 20 mg of Hydroxocobalamin Acetate and dissolve in acetic acid-sodium acetate
buffer solution, pH 5.0, to make exactly 50 mL. Pipet
exactly 2 mL of this solution into a 50-mL volumetric
flask, add 1 mL of a solution of potassium cyanide (1 in
1000) and allow to stand for 30 minutes at ordinary temperature. Add acetic acid-sodium acetate buffer solution,
pH 5.0, to make exactly 50 mL and use this solution as
mg of cyanocobalamin RS after determining the loss on
drying in the same manner as for Cyanocobalamin and
dissolve in water to make exactly 50 mL. To 2 mL of this
solution, exactly measured, add acetic acid-sodium acetate buffer solution, pH 5.0, to make exactly 50 mL and
KP 9 487
absorbances, AT and AS, of the test solution and the standard solution, respectively, at 361 nm as directed under
Amount (mg) of hydroxocobalamin acetate
(C62H89CoNl3O15PC2H4O2)
= amount (mg) of cyanocobalamin RS, calculated on
AT
the dried basis A 1.0377
S
Hydroxychloroquine Sulfate
Cl
H
N
N
N
CH3
CH3
H2SO4
OH
C18H26ClN3OH2SO4 : 433.95
Hydroxychloroquine Sulfate contains not less than
98.0% and not more than 102.0% of hydroxychloroquine
sulfate (C18H26ClN3OH2SO4), calculated on the anhydrous basis.
Description Hydroxychloroquine Sulfate is a white,
crystalline powder, is odorless, and has bitter taste.
Hydroxychloroquine Sulfate is freely soluble in water,
and practically insoluble in ethanol, in chloroform, and
in ether.
Hydroxychloroquine Sulfate shows polymorphism.
The ordinary form of Hydroxychloroquine Sulfate melts
at about 240 C, while other forms melt at about 198 C.
solutions of Hydroxychloroquine Sulfate and Hydroxychloroquine Sulfate RS in diluted hydrochloric acid (1
in 100) (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared absorption spectra of Hydroxychloroquine Sulfate and Hydroxychloroquine Sulfate RS, previously dried, as directed in the potassium
bromide disk method under lnfrared Spectrophotornetry:
(3) A solution of Hydroxychloroquine Sulfate (1 100)
Purity Related substancesDissolve 0.10 g of Hydroxychloroquine Sulfate in a mixture of methanol and
water (90 : 10) to make exactly 10 mL, and use this solution as the test solution. Separately, weigh exactly a por-
tion of Hydroxychloroquine Sulfate RS, dissolve in a

mixture of methanol and water (90 : 10) to make solutions containing 0.01, 0.05, 0.1, and 0.2 mg per mL, respectively, and use these solutions as the standard solutions. Perform the test with these solutions as directed
of the test solution and standard solutions on a plate of
silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethanol,
water and ammonia solution (28) (80 : 16 : 4) to a distance of about 15 cm, and air-dry the plate. Examine under ultraviolet light (main wavelengths: 254 nm and 366
solution are not more intense than the spots from the
standard solution.
Loss on Drying Not more than 2.0% (105 C, 2 hours).
Assay Weigh accurately about 0.1 g each of Hydroxychloroquine Sulfate and Hydroxychloroquine Sulfate
RS, dissolve in 5 mL of water, and add diluted hydrochloric acid (1 in 100) to make exactly 100 mL. Pipet exactly 1.0 mL each of these solutions, add diluted hydrochloric acid (1 in 100) to make exactly 100 mL, and
solution, respectively. Perform the test with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry. Determine the absorbances, AT and AS, of the test solution and the standard solution, respectively, at the wavelength of maximum absorbance near 343 nm.
Amount (mg) of hydroxychloroquine sulfate

AT
(C18H26ClN3OH2SO4) = 10 C A
S
C: Concentration of Hydroxychloroquine Sulfate RS
in the standard solution (g/mL).
Hydroxyprogesterone Caproate
H3C
H3C
H3C
O
CH3
O
O
C27H40O4: 428.60
Hydroxyprogesterone Caproate, contains not less than
97.0% and not more than 103.0% of hydroxyprogesterone caproate (C27H40O4), calculated on the anhydrous

basis.
Description Hydroxyprogesterone Caproate is a white
to milky white crystalline powder and is odorless or has
slight odor.
Hydroxyprogesterone Caproate is soluble in ether,
slightly soluble in benzene and practically insoluble in
water.
Identification Determine the infrared absorption spectra of Hydroxyprogesterone Caproate and hydroxyprogesterone caproate RS, previously dried in vacuum for 4
hours, according to the potassium bromide disk method
Melting Points Between 120 C and 124 C.
64 (0.1 g, calculated on the anhydrous basis, chloroform,
10 mL, 100 mm).
Purity (1) Free n-caproic acidWeigh about 0.20 g
of Hydroxyprogesterone Caproate and dissolve in 25 mL
of neutralized ethanol. Titrate with 0.02 mol/L sodium
hydroxide VS: not more than 0.50 mL of 0.02 mol/L sodium hydroxide is required (0.58%).
(2) Related compoundsWeigh accurately about 0.1
g of Hydroxyprogesterone Caproate, dissolve in 10 mL
of chloroform and use this solution is the test solution.
Separately, weigh accurately about 10 mg of Hydroxyprogesterone Caproate RS, previously dried for 4 hours
in vacuum (silica gel) and dissolve in chloroform to
make 10 mL. Pipet exactly 0.1 mL, 0.5 mL, 1.0 mL and
2.0 mL of this solution, add 10 mL of acetone exactly
and use these solutions as standard solutions (1), (2), (3)
and (4), respectively. Perform the test with the test solution and the standard solutions (1), (2), (3) and (4), as directed under Thin Layer Chromatography. Spot 20 L
each of the test solution and the standard solutions (1),
(2), (3) and (4) on silica gel plate for the thin layer chromatography. Develop the plates with a mixture chloroform and ethyl acetate (3:1) to a distance about 15 cm
and air-dry the plate. Spray a mixture of sulfuric acid and
ethanol (1 : 9), prepared by adding sulfuric acid slowly
and carefully to ethonal on an ice-bath, on the plates thoroughly and heat the plates until it charr. Using ultraviolet light (main wavelength 366 nm), the relative intensities of the spots from the test solution, except the principal spot, compared to that of each standard solution is
not more than 2.0%.
direct titration).
Assay Weigh accurately about 50 mg each of Hydroxyprogesterone Caproate and Hydroxyprogesterone Caproate RS, previously dried in vacuum in a dessicator (si-
lica gel) for 4 hours, dissolve in ethanol to make exactly

100 mL and mix by shaking. Pipet exactly 2 mL each of
these solutions, add ethanol to make exactly 100 mL and
solution, respectively. Perform the test with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry. Determine the absorbances, AT and AS, of the test solution and the standard solution, respectively, at the wavelength of maximum absorbance near 240 nm.
Amount (mg) of Hydroxyprogesterone Caproate
AT
(C27H40O4) = 5 C A
S
C: Concentration of the standard solution (g/mL).
Hydroxyprogesterone Caproate
Injection
Hydroxyprogesterone Caproate Injection is an oily injection. Hydroxyprogesterone Caproate Injection contains
not less than 90.0% and not more than 110.0% of the labeled amount of hydroxyprogesterone caproate
(C27H40O4: 428.60).
Method of Preparation Prepare as directed under Injections, with Hydroxyprogesterone Caproate.
Identification (1) Transfer a volume of Hydroxyprogesterone Caproate Injection, equivalent to 0.125 g of Hydroxyprogesterone Caproate according to the labeled
amount, to a separatory funnel containing 10 mL of hexane, 8 mL of methanol and 2 mL of water and shake for 2
minutes and stand to separate. Titrate 3 mL of lower
layer with sulfuric acid until the color of solution appears.
Add 3 mL of methanol: violet color appears. Light with
long wavelength ultraviolet line shows a pale yellowish
fluorescence.
(2) Evaporate 4 mL of the test solution of the Assay
to dryness by heating in a water-bath. Dissolve the residue in 0.5 mL of chloroform and use this solution as the
test solution. Dissolve a suitable amount of Hydroxyprogesterone Caproate RS in a suitable amount of chloroform so as to contain 400 g of hydroxyprogesterone
caproate per mL. Use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin Layer Chromatography. Spot 10 L each of the test solution and the
standard solution on a plate of silica gel. Develop the
plates with a mixture of chloroform and ethyl acetate (3 :
1) at a distance about 10 cm and air-dry. Spray a mixture
of sulfuric acid and ethanol (1 : 3) on these plates tho-
KP 9 489
roughly and heat the plates at 105 C for 5 minutes: the
Rf value of the principal yellowish green spot obtained
from the test solution corresponds to that from the standard solution.
direct titration).
It

Assay Take accurately a volume of Hydroxyprogesterone Caproate Injection, equivalent to 0.25 g of hydroxyprogesterone caproate (C27H40O4) according to the labeled amount, add methanol to make 250 mL and mix.
Pipet exactly 5 mL of this solution, add methanol to
make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately about 50 mg of Hydroxyprogesterone Caproate RS, previously dried in vacuum in a desicator for 4 hours, add methanol to make
as the standard solution. Pipet exactly 5 mL each of the
test solution and the standard solution to a stopered flask
and add 10.0 mL of the isonicotinic acid hydrazide solution. Mix and allow to stand at 30 C on a water-bath for
about 45 minutes. Determine the absorbances of these
solutions as directed under the Ultraviolet-visible Spectrophotometry, AT and AS, at the wavelength of maximum
absorbance near 380 nm, using a mixture of methanol
and the isonicotinic acid hydrazide solution (1 : 2) as a
blank.
Amount (mg) of hydroxyprogesterone caproate

(C27H40O4) = amount (mg) of Hydroxyprogesterone
AT
Caproate RS A 5
S
Isonicotinic acid hydrazide solutionDissolve 0.375
g of Isonicotinic Acid Hydrazide in 0.47 mL of hydrochloric acid and 500 mL of methanol.
Hydroxyzine Hydrochloride
CH2CH2OCH2CH2OH
2 HCl
C
H
and enantiomer

Cl
C21H27ClN2O22HCl: 447.83
Hydroxyzine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of hydroxyzine hydrochloride (C21H27ClN2O22HCl).
Description Hydroxyzine Hydrochloride is a white,
Hydroxyzine Hydrochloride is very soluble in water,
freely soluble in methanol, in ethanol or in anhydrous
acetic acid, very slightly soluble in acetic anhydride and
Identification (1) Take 5 mL of a solution of Hydroxyzine Hydrochloride (1 in 100), add 2 to 3 drops of ammonium thiocyanate-cobaltous nitrate TS: a blue precipitate is produced.
Hydroxyzine Hydrochloride and Hydroxyzine Hydrochloride RS in methanol (1 in 100000) as directed under
(3) A solution of Hydroxyzine Hydrochloride (1 in
pH Dissolve 1.0 g of Hydroxyzine Hydrochloride in 20
2.5.
g of Hydroxyzine Hydrochloride in 10 mL of water: the
(2) Heavy metalsProceed with 1.0 g of Hydroxyzine Hydrochloride according to Method 2 and perform
(3) Related substancesDissolve 0.20 g of Hydroxyzine Hydrochloride in 10 mL of methanol and use this
test solution, add methanol to make exactly 200 mL and
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, ethanol and

ammonia water (28) (150 : 95 : 1) to a distance of about
10 cm and air-dry the plate. Allow the plate to stand in
iodine vapor: the spots other than the principal spot from
hours).
Assay Weigh accurately about 0.1 g of Hydroxyzine
mixture of acetic anhydride and anhydrous acetic acid
(7 : 3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection method in Titrimetry). Perform a blank determination and make any

= 22.392 mg of C21H27ClN2O22HCl
Package and Storage Preserve in tight containers.
Hydroxyzine Pamoate
CO2H
Cl
N
OH
CH2CH2OCH2CH2OH
CH2
C
H
OH
CO2H
and enantiomer
C2lH27ClN2O2C23H16O6: 763.27
Hydroxyzine Pamoate contains not less than 98.0% and
not more than 101.0% of Hydroxyzine Pamoate
(C2lH27ClN2O2C23H16O6), calculated on the anhydrous
basis.
Description Hydroxyzine Pamoate is a pale yellow,
taste.
Hydroxyzine Pamoate is freely soluble in dimethylformamide, slightly soluble in acetone and practically insoluble in water, in methanol, in ethanol or in ether.
Identification (1) Take 0.1 g of Hydroxyzine Pamoate,
add 25 mL of sodium hydroxide TS and shake vigorously.
Extract with 20 mL of chloroform and use the chloroform layer as the test solution. Reserve the water layer
for (2). Take 5 mL of the test solution, add 2 mL of ammonium thiocyanate-cobaltous nitrate TS, shake and allow to stand: a blue color is observed in the chloroform
layer.
(2) Take 1 mL of the water layer obtained in (1), add

2 mL of 1 mol/L hydrochloric acid TS: a yellow precipitate is produced. Collect the precipitate, dissolve the precipitate in 5 mL of methanol and add 1 drop of ferric
chloride TS: a green color is observed.
(3) Take 2 mL of the test solution obtained in test (1),
evaporate the test solution on a water-bath to dryness,
dissolve the residue in 0.1 mol/L hydrochloric acid TS to
make 500 mL. Determine the absorption spectrum of the
solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 231 nm
and 233 nm.
(4) Perform the test with Hydroxyzine Pamoate as directed under the Flame Coloration Test (2): a green color
is observed.
g of Hydroxyzine Pamoate in 10 mL of dimethylformamide: the solution is clear and shows a slightly greenish,
pale yellow-brown color.
(2) ChlorideTake 0.3 g of Hydroxyzine Pamoate,
add 6 mL of dilute nitric acid and 10 mL of water, shake
for 5 minutes and filter. Wash the residue with two 10
mL volumes of water, combine the washings with the filtrate and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control
solution with 0.80 mL of 0.01 mol/L hydrochloric acid
(3) Heavy metalsProceed with 1.0 g of Hydroxyzine Pamoate according to Method 2 and perform the
Hydroxyzine Pamoate according to Method 3 and perform the test (not more than 1 ppm).
(5) Related substancesDissolve 0.40 g of Hydroxyzine Pamoate in 10 mL of a mixture of sodium hydroxide TS and acetone (1 : 1) and use this solution as the test
solution. Pipet exactly 1 mL of this solution, add a mixture of sodium hydroxide TS and acetone (1 : 1) to make
exactly 20 mL. Pipet exactly 5 mL of this solution, add a
mixture of sodium hydroxide TS and acetone (1 : 1) to
standard solution as directed under the Thin-layer chromatography. Spot 5 L each of the test solution and the
ethyl acetate, ethanol and ammonia water (150 : 95 : 1)
evenly chloroplatinic acid-potassium iodide TS on the
plate: the spots other than the spots from hydroxyzine
and pamoic acid obtained from the test solution are not
more intense than the spots from the standard solution.
direct titration).
KP 9 491
Assay Weigh accurately about 0.6 g of Hydroxyzine

Pamoate, add 25 mL of sodium hydrolride TS, shake
and extract with six 25 mL volumes of chloroform. Filter
each extract through 5 g of anhydrous sodium sulfate on
a pledget of absorbent cotton. Combine the chloroform
extracts and evaporate the combined chloroform extracts
on a water-bath to about 30 mL. Add 30 mL of anhydrous acetic acid and titrate with 0.1 mol/L perchloric acid
VS until the color of the solution changes from purple
through blue to blue-green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination
and make any necessary connection.

= 38.164 mg of C2lH27ClN2O2C23H16O6
Hymecromone
HO
CH3
C10H8O3: 176.17
Hymecromone, when dried, contains not less than 98.0%
and not more than 101.0% of hymecromone (C10H8O3).
Description Hymecromone is a white crystal or crystalline powder, is odorless and tasteless.
Hymecromone is freely soluble in dimethylformamide,
sparingly soluble in ethanol, in dehydrated ethanol or in
acetone, slightly soluble in ether and practically insoluble in water.
Identification (1) Dissolve 2 mg of Hymecromone in 5
mL of ammonia-ammonium chloride buffer solution, pH
11.0: the solution shows an intense blue-purple fluorescence.
(2) Dissolve 25 mg of Hymecromone in 5 mL of diluted ethanol (1 in 2) and add 1 drop of ferric chloride
TS: initially a blackish brown color is observed and
when allowed to stand the color changes to yellowbrown.
Hymecromone and hymecromone RS in dehydrated
(4) Determine the infrared spectra of Hymecromone
and hymecromone RS, previously dried, as directed in
the potassium bromide disc method under the Infrared

Purity (1) ChlorideDissolve 0.8 g of Hymecromone
in 40 mL of a mixture of acetone and water (2 : 1) and
add 6 mL of dilute nitric acid and a mixture of acetone
and water (2 : 1) to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control solution as follows: to 0.25 mL of 0.01 mol/L hydrochloric
acid VS, add 6 mL of dilute nitric acid and a mixture of
acetone and water (2 : 1) to make 50 mL (not more than
0.011%).
(2) SulfateDissolve 0.8 g of Hymecromone in 40
mL of a mixture of acetone and water (2 : 1) and add 1
mL of dilute hydrochloric acid and a mixture of acetone
and water (2 : 1) to make 50 mL. Perform the test using
VS, add 1 mL of dilute hydrochloric acid and a mixture
of acetone and water (2:1) to make 50 mL (not more than
0.024%).
(3) Heavy metalsProceed with 2.0 g of Hymecromone according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Hymecromone according to Method 3 and perform the
(5) Related substancesDissolve 80 mg of Hymecromone in 10 mL of ethanol and use this solution as the
test solution. Pipet exactly 1 mL of the test solution and
add ethanol to make exactly 50 mL. Pipet exactly 1 mL
of this solution, add ethanol to make exactly 20 mL and
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform and ethanol
Allow the plate to stand in iodine vapor for 5 minutes:
solution.
hours).
Assay Weigh accurately about 0.25 g of Hymecromone,
hydroxide VS (potentiometric titration, Endpoint Detection method in Titrimetry). Separately, perform a blank
determination with a solution prepared by adding 14 mL
of water to 90 mL of dimethylformamide and make any

hydroxide VS = 17.617 mg of C10H8O3

P2O5, not more than 0.67 kPa, 4 hours).
Ibuprofen
CH3
CH3
CHCH2
CH3
CCO 2H
H
and enantiomer
C13H18O2: 206.28
Ibuprofen, when dried, contains not less than 98.5% and

not more than 101.0% of ibuprofen (C13H18O2).
Description Ibuprofen is a white crystalline powder.
and has slightly characteristic smell and taste.
Ibuprofen is very soluble in ethanol, in absolute ethanol,
in acetone and sparingly soluble in water.
Ibuprofen is soluble in sodium hydroxide.
Identification (1) Determine the absorption specta of
solutions of Ibuprofen and Ibuprofen RS in diluted sodium hydroxide TS (1.5 in 10000) as directed under the
Ultraviolet-visible Spectrophotometry: both spectra exhibits similar intensities of absorption at the same wavelengths.
(2) Determine the Infrared absorption specta of Ibuprofen and Ibuprofen RS, previously dried, as detected in
Purity (1) Heavy metalsProceed with 3.0 g of Ibuprofen according to Method 2 and perform the test. Prepare the control solution with 3.0 mL of standard lead solution (not more than 10 ppm).
Ibuprofen according to Method 3 and perform the test
(3) Related substancesDissolve 0.50 g of Ibuprofen in 5 mL of chloroform and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add chloroform to make exactly 100 mL and use this solution as
and the standard solution on a plate of silica gel with fluorescent indicator for Thin-layer chromatography. Develop the plate with a mixture of hexane, ethyl acetate
and glacial acetic acid (15 : 5 : 1) to a distance of about
Assay Weigh accurately about 0.5 g of Ibuprofen, previously dried, dissolve in 50 mL of ethanol and titrate
with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops
of phenolphthalein TS). Perform a blank determination

= 20.628 mg of C13H18O2
Ichthammol
Ichthammol, calculated on the dried basis, contains not
less than 2.5% of ammonia NH3: 17.030), not more not
more than 8.0% of ammonium sulfate [(NH4)2SO4:
132.14] and not less than 10.0% of total sulfur (as S:
32.07).
Description Ichthammol is a red-brown to blackish
brown, viscous fluid and has a characteristic odor.
Ichthammol is miscible with water and is partially soluble in ethanol or in ether.
Identification (1) Take 4 mL of a solution of Ichthammol (3 in 10), add 8 mL of hydrochloric acid: a yellow-brown to blackish brown, oily or resinous mass is
produced. Cool the mass with ice to solidify and discard
the water layer. Wash the residue with ether: a part of the
mass dissolves but it does not dissolve completely even
when it is washed until almost no color develops in the
washing. Perform the following tests with this residue.
(i) Take 0.1 g of the residue, add 1 mL of a mixture of
ether and ethanol (1 : 1): it dissolves.
(ii) Take 0.1 g of the residue, add 2 mL of water: it dissolves. To 1 mL of this solution, add 0.4 mL of hydrochloric acid: a yellow-brown to blackish brown oily or resinous substance is produced.
(iii) Take 1 mL of the solution obtained in (ii), add 0.3 g
of sodium chloride: a yellow-brown or blackish brown
oily or resinous substance is produced.
(2) Boil 2 mL of a solution of Ichthammol (1 in 10)
with 2 mL of sodium hydroxide TS: the gas evolved
changes moistened red litmus paper to blue.
Loss on Drying Not more than 50% (0.5 g, 105 C, 6
hours).
KP 9 493
Assay (1) AmmoniaWeigh accurately about 5 g of

Ichthammol, transfer to a Kjeldahl flask and add 60 mL
of water, 1 mL of octyl alcohol and 4.5 mL of a solution
of sodium hydroxide (2 in 5). Connect the flask to a distilling tube with a spray trap and a condenser and immerse the lower outlet of the condenser in the receiver
containing exactly 30 mL of 0.25 mol/L sulfuric acid VS.
Distil slowly, collect about 50 mL of the distillate and titrate the excess sulfuric acid with 0.5 mol/L sodium hydroxide VS (indicator: 3 drops of methyl red TS). Perform a blank determination and make any necessary correction.

= 8.515 mg of NH3
(2) Ammonium sulfateWeigh accurately about 1 g
of Ichthammol, add 25 mL of ethanol, stir thoroughly
and filter. Wash with a mixture of ether and ethanol (1:1)
until the washings are clear and colorless. Dry the filter
paper and the residue in air, dissolve the residue in 200
mL of hot water acidified slightly with hydrochloric aicd
and filter. Boil the filtrate, add 30 mL of barium chloride
TS slowly, heat for 30 minutes on a water bath and filter.
Wash the precipitate with water, dry and ignite to constant weight. Weigh the residue as barium sulfate (BaSO4: 233.39).
Amount (mg) of ammonium sulfate [(NH4)2SO4]
= amount (mg) of barium sulfate (BaSO4) 0.5662
(3) Total sulfurWeigh accurately about 0.6 g of
Ichthammol, transfer to a 200-mL Kjeldahl flask and add
30 mL of water and 5 g of potassium chlorate, then add
slowly 30 mL of nitric acid and evaporate the mixture to
about 5 mL. Transfer the residue to a 300-mL beaker
with the aid of 25 mL of hydrochloric acid and evaporate
again to 5 mL. Add 100 mL of water, boil, filter and
wash with water. Heat the combined filtrate and washings to boil, add gradually 30 mL of barium chloride TS,
heat the mixture on a water-bath for 30 minutes and filter.
Wash the precipitate with water, dry and ignite to constant weight. Weigh the residue as barium sulfate (BaSO4).
Amount (mg) of total sulfur (S) = amount (mg) of
barium sulfate (BaSO4) 0.13739
Idoxuridine
I
NH
N
HOH 2C
O
H
H
H
OH
C9H11IN2O5: 354.10
Idoxuridine, when dried, contains 98.0% and not more
than 101.0% of idoxuridine (C9H11IN2O5).
Description Idoxuridine is a colorless, crystal or a
white, crystalline powder. Idoxuridine is odorless.
Idoxuridine is freely soluble in dimethylformamide,
slightly soluble in water, very slightly soluble in ethanol
and practically insoluble in ether. Idoxuridine dissolves
in sodium hydroxide TS.
Identification (1) Dissolve 10 mg of Idoxuridine in 5
mL of water by warming, add 5 mL of diphenylamineglacial acetic acid TS and heat for 5 minutes: a blue color
is observed.
(2) Heat 0.1 g of Idoxuridine: a purple gas evolves.
(3) Dissolve 2 mg of Idoxuridine and Idoxuridine TS
in 50 mL of 0.01 mol/L sodium hydroxide VS and determine the absorption specta of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
the same wavelength .
D : Between +28 and
+31 (after drying, 0.20 g, sodium hydroxide TS, 20 mL,
100 mm).
0.20 g of Idoxuridine in 5 mL of a solution of sodium
hydroxide (1 in 200): the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Idoxuridine
(3) Related substancesDissolve about 0.10 g of
Idoxuridine in exactly 10 mL of a mixture of dilute ethanol and strong ammonia water (99 : 1) and use this solution as the test solution. Perform the test with the test solution as directed under the Thin-layer chromatography.
Spot 50 L of the test solution on a plate of silica gel
Develop the plate with a mixture of ethyl acetate and diluted isopropanol (2 in 3) (4 : 1) to a distance of about 10
(main wavelength: 254 nm): no spot other than principal
spot appears.

(4) Iodine and iodideDissolve 0.10 g of Idoxuridine in 20 mL of water and 5 mL of sodium hydroxide
TS and add immediately 5 mL of dilute sulfuric acid under ice-cooling. Allow to stand for 10 minutes with occasional shaking and filter. Transfer the filtrate into a Nessler tube, add 10 mL of chloroform and 3 drops of a solution of potassium iodate (1 in 100), shake for 30 seconds
and allow to stand: the chloroform layer has no more
color than the following control solution.
Control solutionWeigh accurately 0.111 g of potassium iodide and dissolve in water to make 1000 mL. To
exactly 1 mL of this solution, add 19 mL of water, 5 mL
of sodium hydroxide TS and 5 mL of dilute sulfuric acid,
mix and filter. Transfer the filtrate to a Nessler tube and
proceed in the same manner.
60 C, 3 hours).
Assay Weigh accurately about 0.7 g of Idoxuridine,
previously dried, dissolve in 80 mL of dimethylformamide and titrate with 0.1 mol/L tetramethylammonium hydroxide VS until the color of the solution
changes from yellow through yellow-green to blue (indicator: 5 drops of thymol blue-dimethylformamide TS).
correction.

hydroxide VS = 35.410 mg of C9H11IN2O5
tight containers.
Idoxuridine Ophthalmic Solution

Idoxuridine Opthalmic Solution contains not less than
of idoxuridine (C9H11IN2O5: 354.10).
Ophthalmic Solutions, with Idoxuridine.
Description Idoxuridine Opthalmic Solution is a clear,
colorless liquid.
Identification (1) Take a volume of Idoxuridine Ophthalmic Solution, equivalent to 5 mg of Idoxuridine according to the labeled amount, add 5 mL of diphenylamine-glacial acetic acid TS and heat for 20 minutes: a
pale blue color is observed.
(2) Place a volume of Idoxuridine Ophthalmic Solution, equivalent to 5 mg of Idoxuridine according to the
labeled amount, in a porcelain crucible, add 0.1 g of an-
hydrous sodium carbonate, heat slowly, evaporate to

dryness and ignite until the residue is incinerated. Dissolve the residue in 5 mL of water, acidify with hydrochloric acid and add 2 to 3 drops of sodium nitrate TS: a
yellow-brown color is observed. Then add 2 to 3 drops of
starch TS: a deep blue color is observed.
(3) Take a volume of Idoxuridine Ophthalmic Solution, equivalent to 2 mg of Idoxuridine according to the
labeled amount, add 0.01 mol/L sodium hydroxide TS to
make 50 mL. Determine the absorption spectrum of this
solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 277 nm
and 281 nm.
Purity 5-Iodouracil and 2-deoxyuridineTake a volume of Idoxuridine Ophthalmic Solution, equivalent to
4.0 mg of Idoxuridine according to the labeled amount,
add water to make exactly 5 mL and use this solution as
the test solution. Separately, dissolve 12.0 mg of 5iodouracil and 4.0 mg of 2-deoxyuridine RS in water to
make exactly 200 mL. Measure exactly 5 mL of this solution, add water to make exactly 25 mL and use this solution as the standard solution. Perform the test with 10
the following conditions and determine the peak areas of
5-iodouracil and 2-deoxyuridine: the peak areas of 5iodouracil and 2-deoxyuridine of the test solution are not
more than the peak areas of 5-iodouracil and 2deoxyuridine of the standard solution.
Column temperature: Constant temperature of apploximately 25 C
1).
time of 2-deoxyuridine is about 6 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, 2-deoxyuridine and 5-iodouracil are
above operating conditions, the relative standard deviation of the peak area of 2-deoxyuridine is not more than
1.0%.
KP 9 495

tight containers in a cold place and avoid freezing.
Foreign Insoluble Matter Test It meets the requirement

Insoluble Particulate Matter for Ophthalmic Solutions It meets the requirement
Assay Measure exactly a volume of Idoxuridine Ophthalmic Solution, equivalent to 3 mg of Idoxuridine
(C9H11IN2O5) according to the labeled amount, add exactly 2 mL of the internal standard solution, then add water to make 10 mL and use this solution as the test solution. Separately, weigh accurately about 10 mg of Idoxuridine RS, previously dried at 60 C for 3 hours and dissolve in water to make exactly 10 mL. Measure exactly 3
mL of this solution, add exactly 2 mL of the internal
standard solution, then add water to make 10 mL and use
with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of the peak area of Idoxuridine to
that of the internal standard, for the test solution and the
Amount (mg) of idoxuridine (C9H11IN2O5)

= amount (mg) of Idoxuridine RS
QT
3
QS 10
Internal standard solutionA solution of sulfathiazole in mobile phase (1 in 4000).

Column temperature: Constant temperature of apploximately 25 C
13).
time of Idoxuridine is about 9 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, idoxuridine and the internal standard
above operating conditions, the relative standard deviation of the ratios of the peak area of idoxuridine to that of
Ifenprodil Tartrate
CH 2
OH
CH 3
OH
CO 2H
OH
HOOC
2
OH
(C21H27NO2)2C4H6O6: 800.99
Ifenprodil Tartrate contains not less than 98.5% and not
more
than
101.0%
of
ifenprodil
tartrate
[(C21H27NO2)2C4H6O6], calculated on the anhydrous basis.
Description Ifenprodil Tartrate occurs as a white crystalline powder and is odorless.
Ifenprodil Tartrate is freely soluble in glacial acetic acid,
soluble in ethanol, slightly soluble in water or in methanol and practically insoluble in ether.

D Between +11 and
+15 (1.0 g, calculated on the anhydrous basis, ethanol,
20 mL, 100 mm).
solutions of Ifenprodil Tartrate and Ifenprodil Tartrate RS
in methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelenght.
(2) Determine the infrared spectra of Ifenprodil Tartrate and Ifenprodil Tartrate RS as directed in the potassium bromide disc method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Dissolve 0.4 g of Ifenprodil Tartrate in 40 mL of
water by warming. After cooling, add 0.5 mL of ammonia TS to this solution, extract with two 40-mL volumes
of chloroform and collect the water layer. Evaporate 30
mL of the water layer on a water-bath to dryness and after cooling, dissolve the residue in 6 mL of water: the solution responds to the Qualitative Tests for tartrate.
Purity (1) Heavy metalsProceed with 2.0 g of Ifenprodil Tartrate according to Method 2 and perform the
(2) Related substancesDissolve 0.30 g of Ifenprodil Tartrate in 10 mL of diluted ethanol (3 in 4) and use
solution, add diluted ethanol (3 in 4) to make exactly 200
mL and use this solution as the standard solution. Perform the test solution with the test and standard solutions
as directed under the Thin-layer chromatography. Spot

on a plate of silica gel for Thin-layer chromatography.
Develop the plate with a mixture of ethyl acetate, hexane,
n-butanol and strong ammonia water (140 : 40 : 20 : 1) to
chloroplantinic acid-potassium iodide TS evenly on the
plate: the spots other than the principal spot from the test
Residue on Ignition
Assay Weigh accurately about 0.5 g of Ifenprodil Tartrate, dissolve in 50 mL of glacial acetic acid and titrate
with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Determination Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 40.05 mg of (C21H27NO2) 2C4H6O6

Imipenem Hydrate
O
Water Perform the test according to Method 2 under

Heat Analysis Method. Weigh about 5 to 10 mg of Imipenem Hydrate in vacuum, and heat to about 200 C
with increasing temperature by 20 C per minute. Weigh
accurately the mass of the sample about at 150 C, calculate the mass difference between before and after, and
determine the water content (not less than 5.0 % and not
more than 8.0 %).
Imipenem Hydrate and Imipenem RS, add 10 mL of
0.9 % sodium chloride solution and 1 mL of 0.1 % of sodium bicarbonate solution, add 0.001 mol/L phosphate
buffer solution to make exactly 50 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L of each of the
operating conditions, and determine the peak areas, AT,
and AS of imipenem,.
AT
AS
HN
NH
HO
H

imipenem, when Imipenem Hydrate is used in a sterile
preparation.
= Amount [g (potency)] of Imipenem RS
H2O
H3C
Sterility Test It meets the requirement, when Imipenem Hydrate is used in a sterile preparation.
Amount [g (potency)] of imipenem (C12H17N3O4S)
HO
tion, pH 7.0, 10 mL, 100 mm).
C12H17N3O4SH2O: 317.36
Imipenem Hydrate contains not less than 849 g (potency) and not more than 990 g (potency) of per mg of imipenem (C12H17N3O4S: 299.35), calculated on the anhydrous basis.
Description Imipenem Hydrate is a whtie powder.
Imipenem Hydrate is freely soluble in water, and sparingly soluble in methanol.
Identification Determine the absorption spectra of Imipenem Hydrate and Imipenem RS as directed in the
paste method under Infrared Spectrophotometry, both
same wave numbers.
D : +85 ~ +95(50 mg
calculated on the anhydrous basis, phosphate buffer solu-
Mobile phase: Weigh 2.0 g of sodium 1hexanesulfonate, dissolve in 800 mL of 0.001 mol/L
phosphate buffer solution, adjust the pH of the solution
to 6.8 with phosphoric acid or 5 mol/L sodium hydroxide,
and add 0.001 mol/L phosphate buffer solution to make
1000 mL.
Packaging and Storage Preserve in tight containers (2
~ 5 C).
Imipramine Hydrochloride
KP 9 497
HCl
N
CH3
CH2CH2CH2N
CH3
C19H24N2HCl: 316.87
Imipramine Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of imipramine
hydrochloride (C19H24N2HCl).
Description Imipramine Hydrochloride is a white to
pale yellowish white, crystalline powder and is odorless.
Imipramine Hydrochloride is freely soluble in water or in
Imipramine Hydrochloride is gradually affected by light.
Identification (1) Dissolve 5 mg of Imipramine Hydrochloride in 2 mL of nitric acid: a deep blue color is
observed.
(2) Dissolve 5 mg of Imipramine Hydrochloride and
Imipramine Hydrochloride TS in 250 mL of 0.01 mol/L
hydrochloric acid TS and determine the absorption spectrum of this as directed under the Ultraviolet-visible
(3) Dissolve about 50 mg of Imipramine Hydrochloride in 5 mL of water, add 1 mL of ammonia TS, allow to
stand for 5 minutes, filter and acidify the filtrate with dilute nitric acid: it responds to the Qualitative Tests (2) for
chloride.
g of Imipramine Hydrochloride in 10 mL of water: the
solution is clear and has no more color than the following control solution.
Control solutionTake exactly 1.0 mL of cobaltous

chloride colorimetric stock solution, 2.4 mL of ferric
chloride CS, 0.4 mL of cupric sulfate colorimetric stock
solution and 6.2 mL of diluted hydrochloric acid (1 in
40) and mix. Pipet 0.5 mL of this solution and add exactly 9.5 mL of water.
(2) IminodibenzylDissolve 50 mg of Imipramine
Hydrochloride in 10 mL of a mixture of hydrochloric acid and ethanol (1 : 1) in a brown volumetric flask. Cool
the flask in ice-water, add 5 mL of an ethanol solution of
furfural (1 in 250) and 5 mL of hydrochloric acid and allow to stand at 25 C for 3 hours. Add a mixture of hydrochloric acid and ethanol (1 : 1) to make 25 mL and
determine the absorbance of this solution at 565 nm as
not more than 0.16.
(3) Related substancesDissolve 0.20 g of Imipra-
mine Hydrochloride in 10 mL of ethanol and use this solution as the test solution. Pipet 1.0 mL of this solution
and add ethanol to make exactly 50 mL. Pipet 5.0 mL of
this solution, add ethanol to make exactly 50 mL and use
plate of silica gel for Thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, glacial acetic
acid, hydrochloric acid and water (11 : 7 : 1 : 1) to a distance of about 12 cm and air-dry the plate. Spray evenly
potassium dichromate-sulfuric acid TS on the plate: the
Loss on Drying Not more than 0.5% (1 g, 105C, 2
hours).
Assay Weigh accurately about 0.3 g of Imipramine
of water. Add 5 mL of sodium hydroxide TS and extract
with three 20 mL volumes of chloroform. Filter each extract through a pledget of absorbent cotton on which a
small quantity of anhydrous sodium sulfate is placed.
Combine the chloroform extracts and titrate with 0.1
mol/L perchloric acid VS until the yellow solution
changes to red-purple (indicator: 10 drops of metanil yellow TS). Perform a blank determination and make any

= 31.687 mg of C19H24N2HCl
tight containers.
Imipramine Hydrochloride
Tablets
Imipramine Hydrochloride Tablets contain not less than
of the imipramine hydrochloride (C19H24N2HCl: 316.87).
Method of Preparation Prepare as directed under Tablets, with Imipramine Hydrochloride.
Identification (1) Weigh a quantity of powered Imipramine Hydrochloride Tablets, equivalent to 0.25 g of
Imipramine Hydrochloride according to the labeled
amount, add 25 mL of chloroform and filter after shaking
well. Evaporate the filtrate on a water-bath. Proceed with
the residue as directed in the Identification (1) under Im-

ipramine Hydrochloride.
(2) Dissolve an amount of the residue obtained in (1),
equivalent to 5 mg of Imipramine Hydrochloride, in 250
mL of 0.01 mol/L hydrochloric acid TS and determine
the absorption spectrum as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 249 nm and 253 nm and a shoulder between 270
nm and 280 nm.
(3) Dry the residue obtained in (1) at 105 for 2
hours: the residue melts between 170 and 174
(with decomposition)
Dissolution Test Perform the test with 1 tablet of Imipramine Hydrochloride Tablets at 75 revolutions per
using pH 6.8 phosphate buffer solution (1 in 2) as the
dissolution solution. Take more than 20 mL of the dissolved solution after 60 minutes from the start of the dissolution test and filter through a membrane filter with
pore size of not more than 0.8 m. Discard the first 10
mL of the filtrate, pipet the subsequent V mL, add the diluted pH 6.8 phosphate buffer solution (1 in 2) to make
exactly V mL so that each mL of the filtrate contains
about
10
g
of
imipramine
hydrochloride
(C19H24N2HCl) according to the labeled amount and use
this solution as the test solution. Separately, weigh accurately 0.025 g of Imipramine Hydrochloride RS, previously dried at 105 C for 2 hours, dissolve in the diluted pH 6.8 phosphate buffer solution (1 in 2) to make
exactly 100 mL. Pipet 4.0 mL of this solution, add the 1st
fluid to make exactly 100 mL and use this solution as the
standard solution. Determine the absorbances, AT and
AS , of the test solution and the standard solution at the
wavelength of 250 nm as directed under the Ultravioletvisible Spectrophotometry, respectively.
The dissolution rate of Imipramine Hydrochloride Tablets in 60 minutes should be not less than 75%.

of imipramine hydrochloride (C19H24N2HCl)
= WS
AT V ' 1
36
AS V
C
WS : Amount (mg) of Imipramine Hydrochloride RS,

C: Labeled amount (mg) of imipramine hydrochloride
(C19H24N2HCl) in 1 tablet.

Assay Take 20 Imipramine Hydrochloride Tablets, add
exactly 200 mL of 0.01 mol/L hydrochloric acid TS and
shake well until the tablets are completely disintegrated.
After centrifuging the solution, pipet a volume of the superantant liquid, equivalent to about 0.025 g of imipramine hydrochloride (C19H24N2HCl) according to the labeled amount, add 0.01 mol/L hydrochloric acid TS to
make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately about 0.025 g of Im-
ipramine Hydrochloride for Assay, previously dried at

105 C for 2 hours, dissolve in 0.01 mol/L hydrochloric
acid TS to make exactly 100 mL and use this solution as
the standard solution. Pipet 3.0 mL each of the test solution and the standard solutions into separators which
contain 15 mL of potassium biphthalate buffer solution,
pH 5.6, 8 mL of bromocresol green-sodium hydroxide
TS and 30 mL of chloroform and shake. Filter the chloroform layer through a pledget of absorbent cotton into a
100 mL volumetric flask. Repeat the extraction with two
30-mL portions of chloroform, combine the chloroform
layers in the 100-mL volumetric flask and add chloroform to make exactly 100 mL. Perform the test with
these solutions as directed under the Ultraviolet-visible
Spectrophotometry, using a solution obtained by proceeding with 3 mL of 0.01 mol/L hydrochloric acid TS in
the same manner as blank. Determine the absorbances,
AT and AS , for the test solution and the standard solution, respectively, at 416 nm .
Amount (mg) of imipramine hydrochloride
(C19H24N2HCl) = amount (mg) of Imipramine
Hydrochloride for Assay
AT
AS
Indapamide
O
N
O
S
NH2
N
H
CH3
Cl
C16H16ClN3O3S : 365.84
Indapamide contains not less than 98.0% and not more
than 101.0% of indapamide (C16H16ClN3O3S), calculated
on the dried basis.
Description Indamaide is a white, crystalline powder.
Indamaide is soluble in methanol, in ethanol, in acetonitril, in glacial acetic acid or in ethyl acetate, slightly soluble in ether or in chloroform, and practically insoluble
in water.
Melting point between 167 and 170 (decomposition).
solution of Indapamide and Indapamide RS in methnol
Spectrophotometry: both spectra exhit similar intensities
of absorption at the same wavelength.
(2) Determine the infrared spectra of Indapamide and
KP 9 499
Indapamide RS as directed in the potassium bromide
disk method under the spectrophotometry: both spectra
Purity Related substancesPerform the test without
exposure to daylight. Dissolve about 0.3 g of Indapamide
in methanol to make exactly 10 mL and use this solution
as the test solution. Separately, dissolve 30 mg of Indapamide RS in methanol to make exactly 100 mL, and use
this solution as the standard solution (1). Add methanol
to 10 mL of the standard solution (1) to make exactly 20
mL, and use this solution as the standard solution (2).
And, add methanol to 10 mL of the standard solution (2)
to make exactly 20 mL, and use this solution as the standard solution (3). Perform the test with these solutions as
directed under the Thin-layer Chromatography. Spots
separately, 10 L of the test solution, 10 L each of the
standard solution (2) and the standard solution (3) on a
plate of silica gel with fluorescent indicator for the Thinlayer Chromatography. Develop the plate with a mixture
of toluene, ethyl acetate and glacial acetic acid (70:30:1)
to a distance of about 15 cm. Remove the plate from the
developing chamber, and air-dry the plate. Examine under ultraviolet light(main wavelength: 254 m), and
compare the intensities of any secondary spots observed
in the chromatogram of the test solution with those of the
principal spots in the chromatograms of the standard solution: secondary spot from the chromatograms of the
test solution is not larger or more intense than the principal spot obtained from standard solution (2) (0.5%),
and the sum of the intensities of the secondary spots obtained from the test solution is not more than 2.0%.
Loss on Drying
4hours).
Not more than 3.0% (1g, 105 C,

Internal standard solutionWeigh exactly 50 mg of
p-chloroacetanilide, dissolve in methanol to make exactly 10 mL.
Detector : An ultraviolet absorption photometer
(wave length: 254 nm).
Column : A stainless steel column, about 4 mm in inside diameter and about 30 cm in length, packed with between 3 and 10 m in particle diameter octadecylsilanized silica gel for liquid chromatography.
Mobile phase : A mixture of water, acetonitrile, methanol and glacial acetic acid (650:175:175:1).
System suitability
with 5 L of the standard solution, the resolution of pchloroacetanilide peak and Indapamide peak is not less
than 2.0, and symmetry factor of Indapamide peak is not
more than 2.0.
operating conditions: the relative standard deviation of
the peak area of Indapamide is not more than 2.0%.
Indenolol Hydrochloride
OH
CH3
OCH2CCH2NHCH
H
Residue on Ignition
Not more than 0.1%.
Assay Weigh about 0.1 g of Indapamide, accurately

weighed, dissolve in 5.0 mL of the internal standard solution, add the mobile phase to make exactly 100 mL,
weigh accurately about 20 mg of Indapamide RS, dissolve in 1.0 mL of internal standard solution, add the
mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with 5 L
each of the test solution and the standard solution as directed under the Liquid chromatography according to the
following operating conditions. Determine the ratios of
peak areas of Indapamide, QT and QS to the peak
area of the internal standard substance of each solution.
Amount (mg) of indapamide (C16H16ClN3O3S)

= 100 C QT
QS
C : Concentration, in mg per mL, Indapamide RS in
HCl
CH3
HCl
CH3
OCH2CCH2NHCH
OH
CH3
and enantiomer
C15H21NO2HCl: 283.80
Indenolol Hydrochloride is a mixture of 1-(7-indenyl
oxy)-3-iospropylamino-2-propanolmonohydrochloride
and 1-(4-indenyloxy)-3-iospropylamino-2-propanol monohydrochloride. Indenolol Hydrochloride, when dried,
of indenolol hydrochloride (C15H21NO2HCl).
Description Indenolol Hydrochloride is a white to pale
yellow crystal or crystalline powder.
Hydrochloride is freely soluble in water or in glacial
acetic acid, soluble in ethanol, or in chloroform, very
slightly soluble in acetic anhydride, slightly soluble in
ethyl acetate and practically insoluble in ether.
Dissolve 1.0 g of Indenolol Hydrochloride in 10 mL of

Indenolol Hydrochloride is affected in color by light
Identification (1) Dissolve 0.1 g of Indenolol Hydrochloride in 1 to 2 drops of dilute hydrochloric acid
and 5 mL of water and add 1 mL of Reinecke salt TS: a
red-purple precipitate is produced.
Indenolol Hydrochloride and Indenolol Hydrochloride
RS (1 in 50000) as directed under the Ultraviolet-visible
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelength.
(3) Determine the infrared absorption spectra of Indenolol Hydrochloride and Indenolol Hydrochloride RS,
disc method under the Infrared Spectrophotometry: both
wavenumbers.
(4) A solution of Indenolol Hydrochloride (1 in 10)
%
Absorbance E11cm
(after drying, 10 mg, water, 1000 mL).

g of Indenolol Hydrochloride in 10 mL of water: the solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 1.0 g of Indenolol
Indenolol Hydrochloride according to Method 1 and perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Indenolol Hydrochloride in 10 mL of chloroform and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add chloroform to make exactly 100 mL and use
plate of silica gel with a fluorescent indicator for Thinlayer chromatography. Develop the plate with a mixture
of 1,2-dichloroethane, dehydrated ethanol and strong
ammonia water (70 : 15 : 2) to a distance of about 12 cm
P2O5, 4 hours).
Isomer Ratio Dissolve 5 mg of Indenolol Hydrochloride in 1.0 mL of a mixture of ethyl acetate and dehy-
drated trifluoroacetic acid (9 : 1) and use this solution as

the test solution. Perform the test with 2 L of the test
solution as directed under the Gas Chromatography according to the following conditions. Determine the areas
of two adjacent peaks, Aa and Ab , having the retention times of about 16 minutes, where Aa is the peak
area of shorter retention time and Ab is the peak area of
longer retention time: the ratio, Aa /( Aa + Ab ) , is between 0.6 and 0.7.
earth for gas chromatography (150 to 180 m in particle
diameter) coated with 65% phenyl-methyl silicon polymer for gas chromatography at the ratio of 2%.
Column temperature: A constant temperature between 150 C and 170 C.
time of the peak showing earlier elution of the two peaks
of Indenolol Hydrochloride is about 16 minutes.
solution under the above operating conditions and calculate the resolution. Use a column with the resolution between the two peaks being not less than 1.1.
Assay Weigh accurately about 0.5 g of Indenolol Hydrochloride, previously dried, dissolve in 50 mL of a
green (indicator: 3 drops of methylrosaniline chloride

Indigocarmine
O
H
N
NaO3S
N
H
SO3Na
O
Cl6H8N2Na2O8S2: 466.35
Indigocarmine, when dried, contains not less than 95.0%
and not more than 101.0% of indigocarmine
(Cl6H8N2Na2O8S2).
KP 9 501
Description Indigocarmine is blue to dark blue powder

or granules and is odorless.
Indigocarmine is sparingly soluble in water and practically insoluble in ethanol or in ether.
Indigocarmine is hygroscopic.
When compressed, Indigocarmine has a coppery luster.
Identification (1) A solution of Indigocarmine (1 in
100) is dark blue in color. Perform the following tests
with this solution as the test solution: the dark blue color
of each solution disappears.
(i) Add 1 mL of nitric acid to 2 mL of the test solution,
(ii) Add 1 mL of bromine TS to 2 mL of the test solution,
(iii) Add 1 mL of chlorine TS to 2 mL of the test solution.
and
(iv) Add 2 mL of sodium hydroxide TS and 0.2 g of zinc
dust to 2 mL of the test solution and warm.
(2) Dissolve 0.1 g of Indigocarmine and Indigocarmine RS in 100 mL of an ammonium acetate solution (1
in 650). To 1 mL of this solution, add an ammonium acetate solution (1 in 650) to make 100 mL and determine
the Ultraviolet-visible Spectrophotometry: it exhibits a
maximum between 610 nm and 614 nm.
(3) Ignite 1 g of Indigocarmine to carbonize. After
cooling, add 20 mL of water to the residue, shake and filter the mixture: the filtrate responds to the Qualitative
Tests for sodium salt and for sulfate.
pH Dissolve 0.10 g of Indigocarmine in 20 mL of water: the pH of the solution is between 5.0 and 6.0.
Purity (1) Water-insoluble substancesTake 1.00 g
of Indigocarmine, add 200 mL of water, shake and filter
through a tared glass filter (G4). Wash the residue with
water until the blue color of the filtrate becomes practically colorless and dry the residue at 105 o C for 4 hours:
the weight of the residue does not exceed 5.0 mg.
(2) ArsenicPlace 0.8 g of Indigocarmine in a Kjeldahl flask, add 5 mL of sulfuric acid and 5 mL of nitric
acid and ignite gently. Repeat the addition of 2 to 3 mL
of nitric acid occasionally and continue to heat until a colorless to pale yellow solution is obtained. After cooling,
add 15 mL of a saturated ammonium oxalate solution,
heat the solution until dense white fumes are evolved and
concentrate to 2 to 3 mL. After cooling, dilute with water
to make 10 mL and perform the test with 5 mL of this solution as the test solution (not more than 5 ppm).
Loss on Drying
hours).
Not more than 10.0% (1 g, 105 C , 2
Residue on Ignition
Not less than 28.0% and not
more than 38.0% (after drying, 1 g).
Assay Weigh accurately about 0.5 g of Indigocarmine,
previously dried, add 15 g of sodium bitartrate and dissolve in 200 mL of water, boil with bubbling of a stream
of carbon dioxide and titrate, while being hot, with 0.1

mol/L titanium trichloride VS until the color of the solution changes from blue through yellow to orange.
Each mL of 0.1 mol/L titanium trichloride VS
= 23.318 mg of C16H8N2Na2O8S2
tight containers.
Indigocarmine Injection
Indigocarmine Injection is an aqueous solution for injection. Indigocarmine Injection contains not less than
of indigocarmine (Cl6H8N2Na2O8S2: 466.35).
Method of Preparation Prepare as directed under Injections, with Indigocarmine.
Description Indigocarmine Injection is a dark blue liquid.
Identification (1) Take a volume of Indigocarmine Injection, equivalent to 0.02 g of Indigocarmine according
to the labeled amount, add 1 mL of nitric acid: the dark
blue color of the liquid disappears and a yellow-brown
color develops.
(2) Take a volume of Indigocarmine Injection, equivalent to 0.02 g of Indigocarmine according to the labeled
amount, add 1 mL of bromine TS: the dark blue color
disappears and a yellow-brown color develops.
amount, add 1 mL of chlorine TS: the dark blue color
disappears and a yellow-brown color develops.
amount, add ammonium acetate solution (1 in 650) to
make 1000 mL and determine the absorbance of the solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 610 nm and 614
nm.
Insoluble Particulate Matter Test
quirement.
It meets the re-

Assay Measure exactly a volume of Indigocarmine In-

jection, equivalent to about 0.2 g of indigocarmine
(Cl6H8N2Na2O8S2), add 6 g of sodium bitartrate and dissolve in water to make 200 mL. Then boil under a carbon
dioxide stream and proceed as directed in the Assay under Indigocarmine.
Each mL of 0.1 mol/L titanium trichloride VS
= 23.318 mg of Cl6H8N2Na2O8S2
hermetic, colored containers may be used.
KP 9 503
Indomethacin
O
C
CH3O
Cl
CH3
CH2COOH
C19H16ClNO4: 357.79
Indometacin, when dried, contains not less than 98.0%
and not more than 101.0% of indometacin
(C19H16ClNO4).
Description Indometacin is a white to pale yellowish
white, very fine crystalline powder.
Indometacin is sparingly soluble in methanol, in ethanol
or in ether and practically insoluble in water.
Indometacin dissolves in sodium hydroxide TS.
Indometacin is colored by light
Identification (1) Dissolve 2 mg of Indomethacin in
100 mL of methanol and determine the absorption spectrum of this solution as directed under the Ultravioletvisible Spectrophotometry: it exhibits a maximum between 317 nm and 321 nm.
(2) Determine the infrared spectra of Indometacin
and Indometacin RS, as directed in the potassium bromide disc method under the Infrared Spectrophotometry:
the same wavenumbers. If any difference appears between the spectra, recrystallize the test and the RS with
ether, filter and dry the crystals and perform the test with
the crystals.
(3) Perform the test with Indomethacin as directed
Purity (1) AcidTake 1.0 g of Indomethacin, add 50
mL of water, shake for 5 minutes and filter. To the filtrate, add 0.20 mL of 0.1 mol/L sodium hydroxide VS
and 1 drop of phenolphthalein TS: a red color develops.
(2) Heavy metalsProceed with 1.0 g of Indometacin according to Method 2 and perform the test. Prepare
Indomethacin according to Method 3 and perform the
(4) Related substancesDissolve 0.10 g of Indomethacin in 10 mL of methanol and use this solution as the
methanol to make exactly 50 mL. Pipet 5.0 mL of this
this solution as the standard solution, Perform the test
with the test solution and the standard solutions as directed under the Thin-layer chromatography. Spot 25 L
of dehydrated ether and glacial acetic acid (100 : 3) to a
hours).
Assay Weigh accurately about 0.7 g of Indomethacin,
previously dried, dissolve in 60 mL of methanol, add 30
mL of water and titrate with 0.1 mol/L sodium hydroxide
VS (indicator: 3 drops of phenolphthalein TS). Perform a

= 35.779 mg of C19H16ClNO4
tight containers.
Indomethacin Capsules
Indomethacin Capsules contain not less than 90.0% and
not more than 110.0%of the labeled amount of indomethacin (C19H16CINO4: 357.79).
Capsules, with Indometacin.
Identification Powder the contents of Indomethacin
Capsules. Take a portion of the powder, equivalent to 0.1
g of Indomethacin according to the labeled amount, add
20 mL of chloroform, shake well and centrifuge. Filter
the supernatant liquid and evaporate the filtrate to dryness. After cooling, dissolve the residue in 20 mL of methanol. To 10 mL of this solution, add methanol to make
50 mL, then to 2 mL of this solution, add methanol to
Determine the absorption spectrum of the test solution as
Purity Related substancesPowder the content of Indomethacin Capsules. Take a portion of the powder,
equivalent to 0.10 g of Indometacin according to the labeled amount, add exactly 10 mL of methanol, shake
well, filter and use the filtrate as the test solution. Dissolve 0.025 g of Indometacin RS in methanol to make

exactly 50 mL. Pipet 1.0 mL of the solution, add methanol to make exactly 10 mL and use this solution as the
standard solution. Proceed as directed in the Purity (4)
under Indomethacin.
Dissolution Test Take 1 capsule of Indomethacin Capsules and perform the test using 900 mL of a mixture of
water and phosphate buffer solution, pH 7.2, (4 : 1) at
100 revolutions per minute as directed in Method 1 under
the Dissolution Test. Take 20 mL or more of the dissolved solution at 20 minutes after starting the test and
filter through a membrane filter (less than 0.8 nm in pore
size). Discard the first 10 mL of the filtrate and use the
subsequent filtrate as the test solution. Separately, weigh
accurately about 0.03 g of Indomethacin RS, previously
dried at 105 C for 4 hours, dissolve in a mixture of water and phosphate buffer solution, pH 7.2, (4 : 1) to make
exactly 1000 mL and use this as the standard solution,
Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 320 nm
as directed under the Ultraviolet-visible Spectrophotometry. The dissolution rate of Indometacin Capsules in 20
minutes should be not less than 75%.

of indometacin (C19H16ClNO4)
= WS
AT 90
AS C
WS : Amount (mg) of Indomethacin RS,

C: Labeled amount (mg) of indomethacin
(C19H16ClNO4) in 1 capsule.

20 Indomethacin Capsules. Powder the combined contents and weigh accurately a portion of the powder,
equivalent to about 0.05 g of indomethacin
(C19H16ClNO4). Dissolve in 40 mL of methanol and add
methanol to make exactly 50 mL. Filter this solution,
discarding the first 10 mL of the filtrate. Pipet the subsequent 5.0 mL of the filtrate, add exactly 3 mL of the internal standard solution, add the mobile phase to make
100 mL and use this solution as the test solution. Separately, weigh accurately about 0.05 g of Indomethacin
RS, previously dried at 105 C for 4 hours and dissolve
in methanol to make exactly 50 mL. Pipet 5.0 mL of the
solution, add exactly 3 mL of the internal standard solution, add the mobile phase to make 100 mL and use this
to the following conditions and calculate the ratios, QT
and QS , of the peak area of Indometacin to that of the
Amount (mg) of indomethacin (C19H16ClNO4)

= amount (mg) of Indomethacin RS
QT
QS

about 25 C.
time of Indometacin is about 8 minutes.
System suitability
System performance: Dissolve 50 mg of 4chhlorobenzoic acid, 30 mg of butyl p-hydroxybenzoate
and 50 mg of Indometacin in 50 mL of methanol. Take 5
mL of this solution add the mobile phase to make 100
mL. When the procedure is run with 20 L of this solution, as directed under the above operating conditions, 4chlorobenzoic acid, butyl p-hydroxybenzoate and Indomethacin are eluted in this order, with the resolution between the peaks of 4-chlorobenzoic acid and butyl phydroxybenzoate being not less than 2.0 and between the
peaks of butyl p-hydroxybenzoate and Indomethacin being not less than 5.
under the above operating conditions, the relative standard deviation of the ratios of the peak area of Indometacin to that of the internal standard is not more than 1.0%.
Indomethacin Suppositories
Indomethacin Suppositories contain not less than 90.0%
and not more than 110.0% of the labeled amount of indometacin (C19H16ClNO4: 357.79).
Suppositories, with Indomethacin.
Identification Dissolve a quantity of Indomethacin
Suppositories, equivalent to 0.05 g of Indometacin according to the labeled amount, in 20 mL of methanol by
warming, add methanol to make 50 mL and filter, if necessary. Take 2 mL of this solution, add methanol to
KP 9 505
Determine the absorption spectrum of the test solution as
Dissolution Test Take 1 capsule of Indometacin Capsules, and perform the test using 900 mL of a mixture of
water and phosphate buffer solution, pH 7.2, (4 : 1) as
the test solution at 50 revolutions per minute as directed
in the method 2. Take 20 mL or more of the dissolved
solution at 60 minutes after startion the test and filter
through a membrane filter (less than 0.8 m in pore size).
Discard the first 10 mL of the filtrate, and use the subsequent filtrate as the test solution. Separately, weigh accurately about 30 mg of indometacin RS, previously dried
at 105 for 4 hours, dissolve in a mixture of water and
phosphate buffer solution, pH 7.2, (4 : 1) to make exactly
1000 mL, and use this as the standard solution. Determine the absorbances, AT and AS of the sample solution and the standard solution at 300 nm as directed under Ultraviolet visible Spectrophotometry. The dissolution rate of Indometacin Capsules in 20 minutes should
be not less than 75%.

of indometacin (C19H16ClNO4)
= WS
AT 90
AS C
WS : Amount (mg) of Indometacin Reference standard.

C : Labeled amount (mg) of indometacin
(C19H16ClNO4) in 1 capsule

Assay Weigh accurately not less than 20 Indomethacin
Suppositories, cut into small pieces carefully and mix
well. Weigh accurately a portion of the mass, equivalent
to about 0.05 g of indometacin (C19H16ClNO4), add 40
mL of tetrahydrofuran, warm at 40 C, dissolve by shaking, cool and add tetrahydrofuran to make exactly 50 mL.
Filter the solution, discard the first 10 mL of the filtrate,
pipet the subsequent 5.0 mL of the filtrate, add exactly 3
mL of the internal standard solution and add the mobile
phase to make 100 mL. Allow the solution to stand for
30 minutes, filter through a membrane filter (0.5 m in
pore size), discard the first 10 mL of the filtrate and use
the subsequent filtrate as the test solution. Separately,
weigh accurately about 0.05 g of Indometacin RS, previously dried at 105 o C for 4 hours and dissolve in tetrahydrofuran to make exactly 50 mL. Pipet 5.0 mL of the
solution, proceed in the same manner as the test solution
the test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculate
the ratios, QT and QS , of the peak area of Indometacin

Amount (mg) of indometacin (C19H16ClNO4)
= amount (mg) of Indometacin RS
QT
QS

Column: A stainless steel column, 4 mm in inside diameter and 10 to 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 to 10
about 25 C.
time of Indometacin is about 8 minutes.
System suitability
System performance: Dissolve 50 mg of 4chlorobenzoic acid, 30 ml of butyl p-hydroxybenzoate
and 50 mg of Indometacin in 50 mL of methanol. Take 5
mL of this solution, and add 95 mLof the mobile phase,
mix. When the procedure is run with 20 L of this solution, as directed under the above operating conditions, 4chlorobenzoic acid, butyl parahydroxybenzoate and Indomethacin are eluted in this order, with the resolution
between the peaks of 4-chlorobenzoic acid and butyl parahydroxybenzoate being not less than 2.0 and beteen the
peaks of butyl p-hydroxybenzoate and Indometacin being not less than 5.0.
System repeatability: When the test is repeated 6 times
above operating conditions, the relative standard deviation of the ratios of peak area of Indometacin to that of
Inositol
HO
OH
HO
OH
HO
Inosit
OH
C6H12O6: 180.16
Inositol, when dried, contains not less than 97.0% and

not more than 101.0% of inositol (C6H12O6).
Description Inositol is a white crystal or crystalline
powder, is odorless and has a sweet taste.
Inositol is very soluble in water, and practically insoluble
in ethanol, ether or chloroform.
Inositol shows no specific optical rotation.
pHThe pH of a solution of Inositol is neutral.
Identification (1) Add 6 mL of nitric acid to 1 mL of
Inositol solution in water (1 in 50). Evaporate in a waterbath and add 0.5 mL of strontium nitrate solution (1 in
10) to the residue. Evaporate in a water-bath again: a redpurple color is observed.
(2) Add 1 mL of lead acetate TS to 4 mL of Inositol
solution in water (1 in 100), shake and mix. Heat in a
water-bath for 5 minutes: the solution changes to a halftransparent gel.
(3) The melting point of hexaacetylinositol obtained
from the Assay is between 212 C and 216 C.
about 1.0 g of Inositol in 10 mL of water: the solution is
(2) ChloridePerform the test with about 2.0 g of
Inositol. Prepare the control solution with 0.30 mL of
(3) SulfatePerform the test with about 4.0 g of Inositol. Prepare the control solution with 0.50 mL of 0.005
mol/L sulfuric acid VS (not more than 0.006%).
(4) Heavy metalsProceed with 1.0 g of Inositol according to Method 1 and perform the test. Prepare the
(5) IronDissolve about 2.0 g of Inositol in 40 mL
of water, add 2 mL of hydrochloric acid, 40 mg of ammonium persulfate and 2 mL of Ammonium thiocyanate
TS: the solution is not more intense than the following
control solution.
Control solutionPrepare in the same manner, using

1.0 mL of standard iron solution instead of Inositol.
(6) CalciumDissolve about 1.0 g of Inositol in 10
mL of water, add 1 mL of Ammonium hydroxide TS and
allow to stand for 1 minute: the solution is transparent.
(7) Reducible substance to Fehlings TSDissolve
about 0.5 g of Inositol in 10 mL of water, add 5 mL of
Fehlings TS, boil for 3 minutes and allow to stand for 30
minutes: no orange-red precipitate is observed.
ours).
Assay Weigh accurately about 0.2 g of Inositol, pre-
viously dried, in a beaker. Add 5 mL of the mixture of 1

mL of dilute sulfuric acid and 50 mL of acetic anhydride,
heat the covered beaker in a water-bath for 20 minutes
and cool in ice. Add 100 mL of water and boil for 20 minutes. After cooling, transfer the substance in a beaker to
a separating funnel, wash the wall of the beaker with a
small volume of water and combine. Extract with 30 mL,
25 mL, 20 mL, 15 mL, 10 mL and 10 mL volumes of
chloroform. Combine all chloroform extracts and wash
with 10 mL of water. Filter the chloroform layer using a
pledget of absorbant cotton, with 10 mL of chloroform.
After combine the filtrate and the washing solution, evaporate on a water-bath and dry at 105 C for 2 hours. After cooling, weigh the substance and it is the weight of
hexaacetylinositol (C18H24O12: 432.38).
Amount (mg) of inositol (C6H12O6)
= amount (mg) of hexaacetylinositol (C18H24O12)
0.4167
Insulin
Insulin is obtained from the pancreas of healthy bovine
or porcine, that has blood sugar-decreasing activity. Potency of Insulin, calculated on the dried basis, is not less
than 26 Insulin units in each mg. Insulin is labeled to indicate the animal species from which it is derived.
Description Insulin is a white, crystalline powder and
is odorless.
Insulin is practically insoluble in water, in ethanol or in
ether.
Insulin dissolves in diluted hydrochloric acid (1 in 360)
or in ether.
Insulin is hygroscopic.
Identification Dissolve 0.01 g of Insulin in 10 mL of
0.1 mol/L hydrochloric acid TS and use this solution as
the test solution. Proceed as the Identification for Insulin
Injection with the test solution.
Purity Clarity and color of solutionDissolve 0.10 g
of Insulin in 10 mL of diluted hydrochloric acid (1 in
360): the solution is clear and colorless to pale yellow.
Zinc Content Weigh accurately about 0.01 g of Insulin,
dissolve in 5 mL of 0.1 mol/L hydrochloric acid TS and
water to make exactly 50 mL. If necessary, dilute the solution with water so as to contain 0.4 to 1.0 g of zinc
(Zn: 65.41) per mL and use this solution as the test solution. Add water to an accurately measured volume of
standard zinc solution for Atomic Absorption Spectrophotometry to make a solution containing 0.3 to 1.2 g
of zinc (Zn: 65.41) per mL and use this solution as the
KP 9 507
and the standard solution as directed under the Atomic
Absorption Spectrophotometry according to the following conditions and determine the amount of zinc in the
test solution using the calibration curve obtained from
the absorbance of the standard solution: the amount of
zinc is not less than 0.27% and not more than 1.08%,
Gas: Combustible gas-Acetylene gas.
Supporting gas-Air.
Lamp: Zinc hollow-cathode lamp.
(4) Standard solution: Dilute two portions of the standard stock solution to make two standard solutions with
the diluent for Insulin, one to contain exactly 2.0 units in
each mL which is designated as the high-dose standard
solution, SH and the other to contain exactly 1.0 unit in
each mL which is designated as the low-dose standard
solution, SL.
(5) Test solution: weigh accurately about 0.02g of Insulin according to the labeled units, dissolve with the diluents for Insulin to make two different test solutions,
one to contain exactly 2.0 units in each mL which is designated as the high-dose test solution, TH and the other to
contain exactly 1.0 unit in each mL which is designated
as the low-dose test solution, TL.
(6) Dose for injection: Select the dose for injection
on the basis of trial or experience. Inject an identical volume, usually 0.3 to 0.5 mL, of the standard solutions
and the test solutions throughout the whole run.
(7) Procedure: Divide the animals into 4 equal groups
of not less than 6 animals each, with least difference in
body weight. Withhold all food, except water, for not less
than 14 hours before the injections and withhold water
during the Assay until the final blood test is taken. Handle the animals with care in order to avoid undue excitement. Inject into each of the animals subcutaneously the
dose of the standard solutions and the test solutions indicated in the following design.
Loss on Drying Not more than 10.0% (0.2 g, 105 C,

16 hours).
Residue on Ignition Weigh accurately 0.02 to 0.04 g
of Insulin in a tared platinum dish, add 2 drops of nitric
acid and heat the dish at first very gently and then strongly to incinerate. Place the dish in a muffle furnace, heat
at 600C for 15 minutes, cool in a desiccator (silica gel)
and weigh: the weight of the residue is not more than
2.5%.
Nitrogen Content Weigh accurately about 0.02 g of
Insulin, dissolve in 10 mL of 0.1 mol/L hydrochloric acid
TS and perform the test as directed under the Nitrogen
Determination: not less than 14.5% and not more than
16.5% of nitrogen (N: 14.01) is found, calculated on the
dried basis.
First group
Second group
Assay (1) Animals: Select healthy rabbits weighing not

less than 1.8 kg. Keep the rabbits in the laboratory not
less than 1 week before use in the Assay by feeding them
with an appropriate uniform diet and water.
(2) Diluent for insulin: Dissolve 1.0 to 2.5 g of phenol or n-cresol in 500 mL of 0.01 mol/L hydrochloric acid VS and add 14 to 18 g of glycerin and 0.01 mol/L hydrochloric acid VS to make 1000 mL.
(3) Standard stock solution: Weigh accurately about
0.02 g of insulin RS and dissolve in the diluent for Insulin to make a standard stock solution containing exactly
20.0 units in each mL. Preserve this solution between
1 C and 15 C and use within 6 months.
Third group TH
Fourth group TL
SH
SL
The second injection should be made on the day after the first injection or within 1 week, using the dose of
the standard solutions and the test solutions indicated in
the following design.
First group
Second group
Third group
Fourth group
TL
TH
SL
SH
At 1 hour and 2.5 hours after the time of injection, obtain a sufficient blood to perform the test from a marginal
ear vein of each animal and determine the blood sugar
content of the blood samples according to (8).
Conversion Table for the blood sugar content (%)

mL*
0.0
0.385
0.382
0.379
0.376
0.373
0.370
0.367
0.364
0.361
0.356
0.1
0.355
0.352
0.350
0.348
0.345
0.343
0.341
0.338
0.336
0.333
0.2
0.331
0.329
0.327
0.325
0.323
0.321
0.318
0.316
0.314
0.312
0.3
0.310
0.308
0.306
0.304
0.302
0.300
0.298
0.296
0.294
0.292
0.4
0.290
0.288
0.286
0.284
0.282
0.280
0.278
0.276
0.274
0.272
0.5
0.270
0.268
0.266
0.264
0.262
0.260
0.259
0.257
0.255
0.253
0.6
0.251
0.249
0.247
0.245
0.243
0.241
0.240
0.238
0.236
0.234
0.7
0.232
0.230
0.228
0.226
0.222
0.222
0.221
0.219
0.217
0.215
0.8
0.213
0.211
0.209
0.208
0.206
0.204
0.202
0.200
0.199
0.197
0.9
0.195
0.193
0.191
0.190
0.188
0.186
0.184
0.182
0.181
0.179
1.0
0.177
0.175
0.173
0.172
0.170
0.168
0.166
0.164
0.163
0.161
1.1
0.159
0.157
0.155
0.154
0.152
0.150
0.148
0.146
0.145
0.143
1.2
0.141
0.139
0.138
0.136
0.134
0.132
0.131
0.119
0.127
0.125
1.3
0.124
0.122
0.120
0.119
0.117
0.115
0.113
0.111
0.110
0.108
1.4
0.106
0.104
0.102
0.101
0.099
0.097
0.093
0.093
0.092
0.090
1.5
0.088
0.084
0.084
0.083
0.081
0.079
0.077
0.075
0.074
0.072
1.6
0.070
0.068
0.066
0.065
0.063
0.061
0.059
0.057
0.056
0.054
1.7
0.052
0.050
0.048
0.047
0.045
0.043
0.041
0.039
0.038
0.036
1.8
0.034
0.032
0.031
0.029
0.027
0.025
0.024
0.022
0.020
0.019
1.9
0.017
0.015
0.014
0.012
0.010
0.008
0.007
0.005
0.003
0.002
*Indicates the volume of 0.005 mol/L sodium thiosulfate VS required in titration. For example, if the
amount was 1.28 mL, the blood sugar content would be 0.127% from the above table.
(8) Blood sugar determination: Place 5.0 mL of a
solution of zinc sulfate (9 in 2000) in a test tube, 18
mm in outside diameter and 165 mm in length, add 1.0
mL of a solution of sodium hydroxide (1 in 250) and
add gently 0.10 mL of the blood sample to the mixture
in the test tube using a blood sugar pipet. Suck up the
supernatant liquid into the pipet, wash out the remaining blood in the inner wall of the pipet and repeat this
procedure. Shake thoroughly the contents in the test
tube and heat the test tube in a water- bath for 3 minutes. Filter the mixture through a funnel, 30 to 40 mm
in diameter in which a pledget of absorbent cotton, previously washed with two 3 mL volumes of warm water,
has been placed, receive the filtrate into a test tube, 30
mm in inside diameter and 90 mm in length, wash the
test tube and the funnel with two 3 mL volumes of water and combine the washings with the filtrate. Add 2.0
mL of alkaline potassium ferricyanide TS, heat in a water-bath for 15 minutes, cool immediately, add 3.0 mL
of potassium iodide-zinc sulfate TS and 2.0 mL of diluted glacial acetic acid (3 in 100) and titrate the liberated iodine with 0.005 mol/L sodium thiosulfate VS
(indicator: 2 to 4 drops of starch-sodium chloride TS).
correction. From the consumed volume (mL) of 0.005
mol/L sodium thiosulfate VS, obtain the blood sugar
content (%) according to the table of the previous page..
(9) Calculation: Sum up the two blood sugar values
of each animal after each injection. Subtract the blood
sugar value effected by the first injection from that effected by the second injection of each animal in the
first group and the third group. The differences are
symbolized as y1 and y3, respectively. Subtract the

blood sugar value effected by the second injection from
that effected by the first injection of each animal in the
second group and the fourth group. The differences are
symbolized as y2 and y4, respectively. Sum up not less
than 6 values of individual differences in the blood
sugar values, y1, y2, y3 and y4 to obtain Y1, Y2, Y3 and Y4,
respectively.
Units in each mg of Insulin
= antilog M units in each mL of the high-dose
b
standard solution a
Yb
M = 0.301 x Y
a
Ya = -Y1+Y2+Y3-Y4
Yb = Y1+Y2+Y3+Y4
a: Mass (mg) of the sample,
b: Total volume (mL) of the high-dose test solution
prepared by diluting the volume of the test with diluent
for Insulin.
Compute L (p = 0.95) by using the following equation:
L should be not more than 0.1212. If L exceeds 0.1212,
repeat the Assay by increasing the number of animals
or improving the Assay conditions in a better way until
L becomes not more than 0.1212.
L = 2 (C 1)(CM 2 + 0.09062)
C=
Yb2
Yb2 4 fs 2 t 2
KP 9 509
s2 =
Y
= Y12
y2 f
n
2
+ Y2 + Y32 + Y42
n = 4( f 1)
f : Number of the animals of each group.
y2 : The sum of spuares of y1, y2, y3 and y4in each
group.
t2 : Value shown in the following table against n for
which s2 is calculated.
n
1
2
3
4
5
6
7
8
9
10
11
12
t2 = F1
161.45
18.51
10.129
7.709
6.608
5.987
5.591
5.318
5.117
4.965
4.844
4.747
n
13
14
15
16
17
18
19
20
21
22
23
24
t2 = F1
4.667
4.600
4.543
4.494
4.451
4.414
4.381
4.351
4.325
4.301
4.279
4.260
n
25
26
27
28
29
30
40
60
120
t2 = F1
4.242
4.225
4.210
4.196
4.183
4.171
4.085
4.001
3.920
3.841

not more than 8 C.
Insulin Injection
Insulin Injection is an aqueous solution for injection.
Insulin Injection contains not less than 95.0% and not
more than 105.0% of the labeled Insulin units.
Method of Preparation Suspend Insulin in water for
injection, dissolve by adding hydrochloric acid and
prepare as directed under Injections. Insulin Injection
contains 0.10 to 0.25 g of phenol or cresol and 1.4 to
1.8 g of concentrated glycerin for each 100 mL of Insulin Injection. Insulin Injection should not contain sodium chloride.
Description Insulin Injection is a clear, colorless or
pale yellow liquid.
Identification Adjust Insulin Injection to pH between
5.1 and 5.3 with a solution of sodium hydroxide (1 in
100): a precipitate is produced. Adjust the solution to a
pH between 2.5 and 3.5 with dilute hydrochloric acid:
the precipitate dissolves.
pH
Between 2.5 and 3.5
Residue on Ignition Measure exactly a volume of
Insulin Injection, equivalent to 500 to 1000 units according to the labeled units, in a tared platinum dish
and evaporate slowly by heating on a water-bath to
dryness. Add 2 drops of nitric acid to the residue and
heat at first very gently, then strongly to incinerate.
Place in a muffle furnace and heat at 600 C for 15 minutes, cool in a desiccator (silica gel) and weigh: the
weight of the residue is not more than 1.0 mg for each
labeled 1000 units.
Nitrogen Content Perform the test as directed under
the Nitrogen Determination: not less than 0.50 mg and
not more than 0.64 mg of nitrogen (N: 14.01) is found
for each labeled 100 units.
It meets the requirement
Assay Proceed with Insulin Injectionn as directed in
the Assay under Insulin, and (5) Test solution and (9)
Calculation are as follows.
(5) Test solution: Aaccording to the labeled units,
dilute Insulin Injection with the diluent for Insulin to
make two different test solutions, one to contain exactly 2.0 units in each mL which is designated as the highdose test solution, TH and the other to contain exactly
1.0 unit in each mL which is designated as the low-dose
test solution, TL.
(9) Calculation: Proceed as directed in the Assay
(9) Calculation under Insulin, using the following equation.
Units in each mg of Insulin = antilog M x units in

b
each mL of the high-dose standard solution a
a: Volume (mL) of the sample.
instead of following equation
Units in each mg of Insulin = antilog M units in
b
each mL of the high-dose standard solution a
a: Mass (mg) of the sample
Packaging and Storage Preserve in hermetic containers, Avoiding freezing in cold place.
Expiration Date 24 months after preparation.
Insulin Zinc Injection

Insulin Zinc Injection (Aqueous Suspension) is an
aqueous suspension for injection. Insulin Zinc Injection
(Aqueous Suspension) contains not less than 90.0%
and not more than 110.0% of the labeled Insulin units
and not less than 0.12 mg and not more than 0.30 mg of
zinc (Zn: 65.41) for each labeled 100 units.
Method of Preparation Prepare as directed under Injections, with Insulin and Zinc Chloride. Each 100 mL
of Insulin Zinc Injection (Aqueous Suspension) contains 0.15 to 0.17 g of sodium acetate, 0.65 to 0.75 g of
sodium chloride and 0.09 to 0.11 g of methyl parahydroxybenzoate.
Description Insulin Zinc Injection (Aqueous Suspension) is a white suspension. When allowed to stand, it
separates into a white precipitate and colorless supernatant liquid and it readily becomes a suspension again on
gentle shaking.
When it is examined microscopically, most part of the
particles in the suspension are crystals, the dimension
of which is mostly 10 to 40 m. Others are amorphous
with less than 2 m.
Identification Adjust the pH of Insulin Zinc Injection (Aqueous Suspension) to between 2.5 and 3.5 with
dilute hydrochloric acid: the particles dissolve and the
pH
Purity Dissolved insulinPerform the test according to Purity (2) of Insulin Zinc Protamine Injection
(Aqueous Suspension).
Nitrogen content Perform the test as directed under
the nitrogen determination: not less than 0.5 mg and not
more than 0.64 mg of nitrogen (N: mol.wt. 14.01) is
found for each labeled 100 Units.

Assay (1) InsulinProceed as directed in the Assay
under the Insulin Injection with the clear liquid obtained from Crystalline Insulin Zinc Injection (Aqueous
Suspension) by adjusting the pH to about 2.5 with diluted hydrochloric acid (1 in 100).
(2) ZincPerform the test according to Assay (2)
of Insulin Zinc Protamine Injection (Aqueous Suspension).
(3) Crystalline insulinMeasure accurately Insulin
Zinc Injection (Aqueous Suspension), equivalent to

about 600 units according to the labeled units, centrifuge, discard the supernatant liquid, suspend the residue in 5 mL of water, add 10 mL of sodium acetateacetone TS, shake for 3 minutes and centrifuge. Discard the supernatant liquid and repeat the above treatment on the residue. Wash down the residue into a
Kjeldahl flask with 15 mL of sulfuric acid and perform
the test as directed under the Nitrogen Determination:
the amount of nitrogen (N: 14.01) is not less than 55.0
and not more than 70.0% of the total nitrogen content.
Calculate the total nitrogen content for insulin units of
a sample from the values of nitrogen obtained in the
Nitrogen content.
Packaging and Storage Preserve in hermetic containers, avoiding freezing in cold place.
Insulin Zinc Protamine

Injection (Aqueous Suspension)
Insulin Zinc Protamine Injection (Aqueous Suspension)
is an aqueous suspension for injection. Insulin Zinc
Protamine Injection contains not less than 90.0% and
not more than 110.0% of the labeled Insulin units and
not less than 0.20 mg and not more than 0.30 mg of
zinc (Zn: 65.41) for each labeled 100 units.
Method of Preparation Prepare as directed under Injections, with Insulin, Protamine Sulfate and Zinc
Chloride. Insulin Zinc Protamine Injection contains
0.38 to 0.63 g of dibasic sodium phosphate, 1.4 to 1.8 g
of concentrated Glycerin and 0.18 to 0.22 g of Cresol
or 0.22 to 0.28 g of Phenol for each 100 mL of Insulin
Zinc Protamine Injection (Aqueous Suspension).
Description
Insulin Zinc Protamine Injection
(Aqueous Suspension) is a white suspension. When allowed to stand, it separates into a white precipitate and
a colorless, supernatant liquid and it readily becomes
suspension again on gentle shaking. When it is examined microscopically, no large particles are seen.
Identification Adjust the pH of Insulin Zinc Protamine Injection (Aqueous Suspension) to between 2.5
and 3.5 with dilute hydrochloric acid: the particles dissolve and the solution is clear and colorless.
pH
Purity (1) ProteinPerform the test as directed under the Nitrogen Determination: not exceeding 1.25 mg
of nitrogen (N: 14.01) is found for each labeled 100
units.
KP 9 511
(2) Dissolved InsulinPerform the following test
with the clear liquid obtained by centrifuging Insulin
Zinc Protamine Injection (Aqueous Suspension): not
more than 2.5% of the labeled units is found. Use a
clear liquid of Insulin Zinc Protamine Injection
(Aqueous Suspension) as the test solution and prepare
the standard solution by proceeding as directed in the
Assay (4) under Insulin Injection to adjust its concentration to 2.5% of the labeled units of Insulin Zinc Protamine Injection (Aqueous Suspension). Divide the
healthy rabbits weighing not less than 1.8 kg, fasted for
not less than 14 hours before injection, into 2 equal
groups of not less than 3. Inject subcutaneously an
amount of the test solution or the standard solution
equivalent to 0.3 units per kg of body weight. Collect
blood before and 1 hour and 2.5 hours after injection,
proceed as directed in the Assay (8) under Insulin Injection and calculate the ratios of the average blood
sugar content in each rabbit measured 1 hour and 2.5
hours after injection to the content before injection: the
mean value for the group injected with the test solution
is not less than the mean value for the group injected
with the standard solution.
Zinc Protamine Injection (Aqueous Suspension),

equivalent to about 200 units according to the labeled
units, add 1 mL of 0.1 mol/L hydrochloric acid TS and
sufficient water to make exactly 200 mL, dilute with
water to contain 0.6 to 1.0 g of zinc in 1 mL and use
this solution as the test solution. Separately, pipet a volume of standard zinc solution for the Atomic Absorption Spectrophotometry, dilute with water to contain
0.4 to 1.2 g of zinc per mL and use this solution as the
and the standard solution according to the Atomic Absorption Spectrophotometry under the following conditions and determine the amount of zinc in the test solution using the analytical curve obtained from the absorbance of the standard solution.
Gas: Combustible gas - Acetylene gas.

Supporting gas - Air.
Packaging and Storage Preserve in hermetic containers. Store at a cold place and avoid freezing.

It meet the requirement.
Assay (1) InsulinProceed as directed in the Assay
under Insulin with the clear liquid obtained by adjusting the pH to 2.5 with diluted hydrochloric acid (1 in
1000) with alterations v) test solution and ix) calculation as follows.
v) Test solution According to labeled units, dilute two
portions of Insurin Zinc Protamine Injection to make
two test solutions with diluents for Insurin, one to contain exactly 2.0 units in each mL which is designated as
the high-dose test solution, TM and the other to contain
exactl 1.0 unit in each mL which is designated as the
low-dose test solution,TL.
ix) Calculation Proceed as directed in the Assay ix)
Calculation under Insurin Injection, using the following
equation.
Units in each mg of Insulin

= antilog M x units in each mL of the high-dose standard solution x b/a
a: Volume (mL) of the sample.
instead of following equation
Unit in each mg of Insurin = antilog M x units in each
mL of the high-dose standard solution
x b/a
a: Mass (mg) of the sample
(2) ZincMeasure accurately a volume of Insulin
Neutral Insulin Injection

Neutral Insulin Injection is an aqueous solution for injection. Neutral Insulin Injection contains not less than
90.0% and not more than 110.0% of the labeled Insulin
units.
the Injections, with Insulin. Neutral Insulin Injection
contains a buffering agent, preservative and isotonizer.
Description Neutral Insulin Injection is a clear, colorless liquid.
Identification Adjust the pH of Neutral Insulin Injection to between 5.1 and 5.3 with dilute hydrochloric acid: a precipitate is produced, dissolves when the pH is
adjusted to between 2.5 and 3.5 with additional dilute
hydrochloric acid: a precipitate is dissolved.
pH
Between 6.9 and 7.8
Purity ZincMeasure exactly a volume of Neutral

Insulin Injection, equivalent to about 200 units according to the labeled units, add 1 mL of 0.1 mol/L hydrochloric acid TS and sufficient water to make exactly
200 mL, dilute with water to make a solution containing 0.4 g, 0.8 g, 1.0 g, 1.2 g and 1.6 g of zinc
(Zn: 65.41) per mL and use this solution as the test solution. Separately, pipet a volume of standard zinc solution for atomic absorption spectrophotometry, dilute
with water to make solutions containing 0.4 g, 0.8 g,

1.0 g, 1.2 g and 1.6 g of zinc (Zn: 65.41) per mL,
respectively, and use these solutions as the standard solutions. Perform the test with the test solution and the
standard solutions as directed under the Atomic Absorption Spectrophotometry according to the following
conditions and determine the amount of zinc in the test
solution using the calibration curve obtained from the
absorbances of the standard solutions: the amount of
zinc (Zn: 65.41) is not more than 40.0 g for each labeled 100 units.
Supporting gas-Air.
Nitrogen Content Measure exactly a volume of Neutral Insulin Injection, equivalent to about 400 units according to the labeled units and perform the test as directed under the Nitrogen Determination: not less than
0.50 mg and not more than 0.64 mg of nitrogen (N:
14.01) is found for each labeled 100 units.
Assay Proceed as directed in the Assay under Insulin
Injection.
Packaging and Storage Preserve in hermetic containers in a cold place and avoid freezing.
Iodamide
COOH
I
CH3COHN
CH2NHCOCH 3
I
C12H11I3N2O4: 627.94
Iodamide contains not less than 98.5% and not more
than 101.0% of iodamide (C12H11I3N2O4), calculated on
the dried basis.
Description Iodamide is a white, crystalline powder
and is odorless.
Iodamide is slightly soluble in water or ethanol, and

Iodamide dissolves in sodium hydroxide TS or sodium
carbonate TS.
The color of Iodamide is gradually colored by light.
Identification (1) Take 10 mg of Iodamide, add 5 mL
of hydrochloric acid and heat in a water-bath for 5 minutes: the solution responds to the Qualitative Tests for
(2) Heat about 0.1 g of Iodamide over a flame: a
purple gas evolves.
(3) Determine the infrared spectra of Iodamide and
Iodamide RS as directed in the potassium bromide disk
method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, weigh 1 g of Iodamide, add 100 mL of water and
dissolve by heating, boil gently and concentrate the solution to about 30 mL. After cooling, collect the separated crystals by filtration, dry and perform the test in
the same manner.
1.0 g of Iodamide in 10 mL of diluted sodium hydroxide TS (1 in 5): the solution is clear and colorless.
(2) Primary aromatic aminesDissolve 0.20 g of
Iodamide in 5 mL of water and 1 mL of sodium hydroxide TS, add 4 mL of a sodium nitrite solution (1 in
100) and 10 mL of 1 mol/L hydrochloric acid TS, shake
well and allow to stand for 2 minutes. To this solution,
add 5 mL of ammonium sulfamate TS, shake thoroughly, allow to stand for 1 minute, add 0.4 mL of a solution
of -naphthol in ethanol (1 in 10), 15 mL of sodium
hydroxide TS and water to make exactly 50 mL and determine the absorbance at 485 nm as directed under the
Ultraviolet-visible Spectrophotometry, using a solution,
prepared in the same manner, as the blank: the absorbance of the solution is not more than 0.12.
(3) Soluble halideDissolve 2.5 g of Iodamide in
20 mL of water and 2.5 mL of ammonia TS and then
add 20 mL of dilute nitric acid and water to make 100
mL. Allow to stand for 15 minutes with occasional
shaking and filter. Discard the first 10 mL of the filtrate,
transfer 25 mL of the subsequent filtrate to a Nessler
tube and add ethanol to make 50 mL. Use this solution
as the test solution and proceed as directed under the
Chloride Limit Test. Prepare the control solution with
0.10 mL of 0.1 mol/L hydrochloric acid VS and 6 mL
of dilute nitric acid and dilute with water to make 25
mL, then with ethanol to 50 mL.
(4) IodineDissolve 0.20 g of Iodamide in 2 mL of
sodium hydroxide TS, add 2.5 mL of 1 mol/L sulfuric
acid TS, allow to stand for 10 minutes with occasional
shaking, then add 5 mL of chloroform, shake vigorously and allow to stand: the chloroform layer remains colorless.
(5) Heavy metalsProceed with 2.0 g of Iodamide
KP 9 513
Iodamide according to Method 3 and perform the test
hours).
Assay Weigh accurately about 0.5 g of Iodamide in a
saponification flask, dissolve in 40 mL of sodium hydroxide TS, add 1 g of zinc dust, connect the flask with
a reflux condenser, boil for 30 minutes, cool and filter.
Wash the flask and filter paper with 50 mL of water and
combine the washings with the filtrate. Add 5 mL of
glacial acetic acid and titrate with 0.1 mol/L silver nitrate VS until the color of the precipitate changes from
yellow to green (indicator: 1 mL of tetrabromophenolphthalein ethyl ester TS).

= 20.931 mg of C12H11I3N2O4
tight containers.
dered iodine with 20 mL of water and filter the mixture.

To 10 mL of the filtrate, add diluted sulfurous acid (1 in
5) drop-wise until the yellow color disappears. Add 1
mL of ammonia TS, followed by 1 mL of silver nitrate
TS in small portions and add water to make 20 mL.
Shake well, filter and after discarding the first 2 mL of
the filtrate, take 10 mL of the subsequent filtrate. To the
filtrate, add 2.0 mL of nitric acid and water to make 20
mL: the solution so obtained has no more turbidity than
the following control solution.
Control solutionTo 0.20 mL of 10 mmol/L hydrochloric acid VS, add 5 mL of water, 2.5 mL of ammonia TS, 1 mL of silver nitrate TS, 2.0 mL of nitric
acid and water to make 20 mL.
Assay Place 1 g of potassium iodide and 1 mL of water in a glass-stoppered flask, weigh accurately, add 0.3
g of Iodine to the flask and weigh accurately again.
Dissolve the iodine by gentle shaking, add 20 mL of
water and 1 mL of dilute hydrochloric acid and titrate
with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL
of starch TS).

= 12.690 mg of I
Iodine
Iodixanol
I: 126.90
OH
Iodine contains not less than 99.5% and not more than
101.0% of iodine (I).
OH
H
N
HO
H
N
OH
OH
Description Iodine is a grayish black plate or heavy,

granular crystal and has a metallic luster and a characteristic odor.
Iodine is freely soluble in ether, soluble in ethanol, sparingly soluble in chloroform and very slightly soluble
in water.
Iodine dissolves in potassium iodide TS.
Iodine sublimes at room temperature.
Identification (1) A solution of Iodine in ethanol (1
in 50) shows a red-brown color.
(2) A solution of Iodine in chloroform (1 in 1000)
shows a red-purple to purple color.
(3) Add 0.5 mL of starch TS to 10 mL of a saturated
solution of Iodine: a dark blue color is observed. When
the mixture is boiled, the color disappears and it reappears on cooling.
Purity (1) Non-volatile residueSublime 2.0 g of
Iodine in a water-bath and dry the residue at 105C for
1 hour: the weight of the residue is not more than 1.0
mg.
(2) Chloride or bromideMix 1.0 g of finely pow-
HO
OH
H
N
H
N
N
OH
O
O
OH
CH3
H3C
O
O
C35H44I6N6O15 : 1550.18
Iodixanol contains not less than 98.6% and not more
than 101.0% of iodixanol (C35H44I6N6O15), calculated
Description Iodixanol is a white, amorphous powder
and is odorless.
Iodixanol is very soluble in water.
Iodixanol is hygroscopic.
Iodixanol and Iodixanol RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) The retention times of the two principal peaks
obtained from the test solution of the related substance
(2) corresponds to these obtained from the standard solution (2) under purity. A third isomer may appear as a

minor peak.
(3) Take about 0.5 g of Iodixanol, in the crucible,
heat: violet vapors are evolved.
+0.5 (1 g, water, 20 mL, 100 mm).
Iodixanol according to Method 1 and perform the test
(not more than 10 ppm). Prepare the control solution
with 1.0 mL of standard lead solution (not more than
10 ppm).
(2) Free iodineWeigh 2.0 g of Iodixanol to a
glass-stoppered tube, add 20 mL of water, 5 mL of toluene, and 5 mL of 1mol/L sulfuric acid TS, shake vigorously, and allow to stand: the toluene layer shows
no red or pink color.
(3) Free iodide Weigh 5.0 g of Iodixanol, add
about 30 mL of water, dissolve and titrate with
0.001mol/L silver nitrate VS. (potentiometric titration,
Endpoint Detection Method in Titrimetry). Not more
than 10 g of iodide per g is found.
Each mL of 0.001N silver nitrate VS

= 126.9 g of I.
(4) Free aromatic amine Weigh accurately about
0.2 g of Iodixanol, dissolve in 15 mL of water, and use
this solution as the test solution. Dissolve an accurately
weighed quantity of Iohexol related substance RS
in water, and prepare a solution containing 10 g per
mL, Add 5 mL of water to 10.0 mL of this solution,
and use this solution as the standard solution. Separately, use 15 mL of water as the blank solution. Place the
standard solution, the test solution, and the blank solution, in an ice bath for 5 minutes. Add 1.5 mL each of 6
mol/L hydrochloric acid, mix by swirling, add 1.0 mL
each of sodium nitrite solution (2 in 100), mix, and allow to stand in the ice bath for 4 minutes. Remove each
solution from the ice bath, add 1.0 mL of 4% sulfamic
acid solution, and swirl gently until gas evolution ceases. Add 1.0 mL of N-(1-Naphthyl) ethylenediamine dihydrochloride solution, a freshly prepared solution of
that in a mixture of propylene goycol and water (70 :
30) mix, add water to make exactly 25 mL, and allow
to stand for 5 minutes. And compare the color: the color obtained from the test solution is lighter than the
color obtained from the standard solution (not more
than 0.05%). If the color obtained from the test solution
is about the same color or darker than the color obtained from the standard solution, concomitantly determine the absorbances of the solutions obtained from
the blank solution, the test solution and the standard solution, AB , AT and AS , as directed under the Ultraviolet Spectrophotometry at the wavelength of maximum absorption of about 495 nm using the water as
blank and 5-cm cells in length (not more than 0.05 %).
Amount (%) of free aromatic amine
C AT AB
W
AS AB
C: Concentration of Iohexol Related Compound II

RS in the standard solution (g /mL).
W: Mass of Iodixanol (mg) taken to prepare the test
solution.
(5) CalciumWeigh accurately about 2.0 g of
Iodixanol, dissolve in 10 mL of water, add 2 mL of internal standard solution, add water to make exactly 20
mL, and use this solution as the test solution. Perpare
a solution containing 10 g of Calcium per 1 mL with
the standard Calcium solution, pipet 0.5, 2.5, 5.0, and
10.0 mL of this solution, add 5.0 mL each of the Internal standard solution, add water to make exactly 50 mL,
and use these solutions as the standard solution (1), (2),
(3) and (4). Pipet 5.0 mL of the internal standard solution, add water to make 50 mL, and use this solution as
the blank test solution. Perform the test with the test solution and the standard solution (1), (2), (3) and (4) as
directed under Atomic absorption spectrophotometry.
Concomitantly determine the absorbances of each standard solution and the test solution at 393.37 nm, the
calcium emission line, and at 361.38 nm, the scandium
emission line, using the blank solution as the blank.
Prepare a calibration line of the ratio of the calcium absorption to the scandium absorption versus the respective calcium concentrations. From the calibration line
so obtained, determine the calcium concentration, C, in
g per mL, in the test solution. Calculate the content of
calcium, in g per g (not more than 5 g per g):
Amount (g /g) of calcium = 20
C
W
W : Mass of Iodixanol (g) taken to prepare the test

solution.
Internal standard solutionAccurately weigh
about 3.067g of scandium oxide, and dissolve in 1000
mL of water, add water to make 1000 mL.
(6) Ionic substancesUse all gloass upparatus
washed with water. Determine the specific conductance
of a solution of Iodixanol (2 in 100), the conductance
of a solution of ionic substancd is not more than a solution of Sodium Cholride (4 g per mL) (not more than
0.02%).
(7) Methanol, isopropyl alcohol, and methoxyethanolTransfer about 0.25 g of Iodixanol, accurately
weighed, to a headspace vial. Add 1.0 mL of the Internal standard solution, seal the vial, mix until dissolved,
and use this solution as the test solution. Weigh accurately about 0.5 g of methanol, about 1.0 g each of isopropanol and methoxyethanol, add water to make exactly 500 mL. Add water to 5.0 mL of this solution to
make exactly 100 mL. Pipet 10.0 mL of this solution
and 1.0 mL of internal standard solution, add water to
KP 9 515
make exactly 100 mL. Pipet exactly 1.0 mL of this solution, seal, and use this solution as the standard solution. This solution contains about 0.005 mg of methanol, 0.01 mg each of isopropanol and methoxyethanol.
Perform the test with 1 mg each of test solution and
standard solution as directed under the Gas Chromatography according to the following operating conditions.
Calculate the ratio of each peak area of methanol Isopropanol and methoxyethanol to the peak area of the
internal standard, QT and QS , respectively. Amount
of methanol, isopropanol and methoxyethanol per1 g of
Iodixanol are not more than 50 g, respectively.
Amount (%) of methanol, isopropanol and methoxyethanol
= 100
C QT
W QS
C : Concentration (mg/mL) of each related substance.

W : Taken amount (mg) of Iodixanol.
Internal standard stock solutionWeigh about 0.5 g of
secondary butyl alcohol, add water to make 500-mL,
and add water to 1.0 mL of this solution to make 100
mL.
Detector: A hydrogen flame ionization detector
(FID)
Column: A capillaray column about 0.54 mm in inside diameter and about 30 m in length, coated with 1
m thickness of polyehtyleneglycol compound (carbowax 20M).
Column temperature: Maintain at 40 for 3 minutes, then it is increased linearly at a rate of 8 C per
minute to 100 C, and is maintained at 100 C for 1
minute.
Carrier gas: Helium
Injection port temperature: 150 C
System suitability
System performance-When the procedure is run
with 1 mL of the standard solution according to the
above operating conditions, methanol, isopropanol, 2butanol and methoxy ethanol are eluted in this order,
with the resolution between methanol peak and isopropanol peak being not less than 1.0.
System repeatability-When the test is repeated 6
above operating conditions, the relative standard deviation of the ratios of the peak area for methanol and for
isopropanol is not more than 0.5%, and the relative
standard deviation of the ratio of the peak area for methoxy ethanol is not more than 10%.
(8) Related substances () Weigh exactly an
amount of Iodixanol, equivalent to about 0.5 g of anhydrous Iodixanol, dissolve in water make exactly 20
mL, use this solution as the test solution (1). Add water
to 5.0 mL of the test solution (1) make esactly 50 mL,
and use this solution as the test solution (2). Separately,
quantitatively, dissolve accurately weighed quantity of
Iodixanol RS, in water to obtain a solution having a
know concentration of about 12.5 mg of anhydrate
Iodixanol per mL, and use this solution as standard
stock solution (1). Quantitatively dissolve an accurately
weighed quantity of Iodixanol related substances RS
in water to obtain a solution having a known concentration of about 0.25 mg of anhydrate iodixanol related
substance per mL, and use this solution as the standard stock solution (2). Quantitatively dissolve an accurately weighed quantity of Iodixanol related substances
II RS in water to obtain a solution having a known concentration of about 0.025 mg of anhydrate iodixanol related substance II per mL, and use this solution as the
standard stock solution (3). Pipet exactly 2.0 mL of the
standard stock solution (1), add water to make exactly
10 mL, and use this solution as the standard solution
(1). Pipet exactly 5.0 mL of the standard stock solution
(1), 2.5 mL of the standard stock solution (2) and 2.5
mL of the standard stock solition (3), add water to
make exactly 25 mL, use this solution as the standard
solution (2).
Pipet exactly 5.0 mL of the test solution (1) and 2.5 mL
of the standard stock solution (2), add water to make
exactly 50 mL, and use this solution as the control solution.
Use water as the blank solution. Perform the test with
10 L each of the blank solution, the test solution (1)
and the test solution (2) as directed under the Liquid
conditions. When it is specified to proceed as directed
for Nigh-low chromatography obtained from test solution (1) and test solution (2), calculate the amount (%)
of each related substance according to the following
formula.
Amount (%) of related substance =
10 X
(1)
0.1Y + Z
X : Peak area of the specified related substance obtained from the test solution(1).
Y : Total area of all the peaks eluted before and after
Iodixanol peak obtained from test solution (1), disgarding any peaks due to injection noise or solvent.
Z : Sum of peak area of the peak of all related substances and the principal peak of Iodixanol obtained
from test solution (2).
IohexolIf Iohexol is present, it exhibits two
peaks with retention times of about 0.37 and 0.39 relative to the principal iodixanol peak, in the chromatogram obtained from test solution (1). Draw a baseline at
the height of the baseline obtained from the blank solution. Calculate the total area of the two peaks and the
amount of iohexol according to the equation(1) (not
more than 0.6%).
Iodixanol related substance IIIIf iodixanol re-

lated substance III is present, it elutes as a single peak
with a retention time of about 0.34 relative to the principal iodixanol peak, in the chromatogram obtained
from test solution (1). Determine the peak area of
Iodixanol revolted substaned III and calculate the
amount of Iodixanol related substance III according
to the equation(1) (not more than 0.2%).
Iodixanol related substance IIf iodixanol related
substance I is present, only the first and larger peak,
with a retention time of about 1.07 relative to the principal iodixanol peak, is seen between the two principal
iodixanol peaks in the chromatogram obtained from
test solution (1); the second iodixanol related substance
I peak co-elutes with iodixanol. The area of the first is
about 80 % of the total area of related substance I, determine the area of the first peak, X2. Calculate the
amount of related substance I by formula (not more
than 0.4%).
Amount (%) of Iodixanol related substance I =
12.5 X 2
(2)
0.1Y + Z
Y and Z are: See formula(1).
Iodixanol related substance IVIf iodixanol related compound IV is present, only the first peak with a
retention time of about 0.8 relative to the principal
iodixanol peak, can be seen in the chromatogram obtained from test solution (1); the second peak co-elutes
with Iodixanol. The area of the first peak corresponds
to about 25% of the total area of Iodixanol related substance IV. Determine the area of the first peak, calculate the amount of iodixanol related substance IV by
following formula (not more than 0.2%).
Amount (%) of Iodixanol related substance IV =

40 X 1
(3)
0.1Y + Z
Iodixanol related substance V If iodixanol related compound V is present, the second peak only,
with a retention time of about 1.18 relative to the last
iodixanol peak, is seen in the chromatogram obtained
from test solution (1); the first peak co-elutes with
iodixanol. The area of the second peak corresponds to
about 85% of the total area of iodixanol related substance V, determine the area of the second peak, X3,
calculate the amount of the related substance V by the
following formula (not more than 0.2 %).
Amount (%) of Iodixanol related substance V =

10 X 3
0.85 (0.1Y + Z )
(4)
Overalkylated related substancesThese compounds exhibit after iodixanol related compound V,

with a retention time greater than 1.18 relative to the
last iodixanol peak in the chromatogram of the test solution(1). Calculate the amount of overalkylated related
substances by the formula (1) determining the amount
of the related substances (not more than 1.0%).
Unspecified related substance 1Determine the
peak area other than the above peak among the peak be
shown before or after iodixanol prineipal peak in the
chromatogram obtained from test solution (1), calculate
the amount of unspecified related substance 1 according to the formula (1).
Other unspecified related substance 2 Determine
the peak area other than the above peak among the peak
be shown between principal peaks of iodixanol in the
chromatogram obtained from the test solution (1), calculate the amount of other unspecified related substance 2. Amounts of each related substances of and
are not more than 2%, and amount of total unspecified related substances is not more than 0.5%.
Total related substancesDetermine total area of
all peaks shown between the principal peaks of iodixanol in the chromatogram obtained from the test solution (1), calculate the amount of total related substance
Amount (%) of total related substances
X 3
X1
X
+ 2 +
100 Y X 1 X 3 +
0.25
0.8
0.85
=
10(0.1Y + Z )
in which the variables are as defined above.

(5m in particle diameter).
Mobile phase: Adjust with mobile phase A and
mobile phase B according to step-wise or the slope of
concentration as follows.
mobile phase A - A mixture of acetonitrile and
water (1 : 1)
mobile phase B - water
Time
(minute)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
94
0 ~ 30
6 20
94 80
30 ~ 70
20 100 80 0
70 ~ 80
80 ~ 81
100
100 6
0
0 94
Elution condition
solvent equilibrium
(about 20 minute)
linear concentration
slope
slope
A constant formation
KP 9 517
slope
81 ~ 90
94
A constant formation

System suitability
Chromatograph the solutions asdirected for procedure, in the following injection sequence : Blank solution, standard solution(1), control solution and at
least three replicates of standard solution(2).
with 10 L of the standard solution (1) according to the
above operating conditions, the chromatogram obtained
from the standard solution (1) exhibits two or three
principal unresolved peaks. If the chromatogram exhibits two principal peaks, their relative areas are about
60% and 40%. If the chromatogram exhibits three principal peaks, their relative areas are about 60%, 38%,
and 2%. When the procedure is run with 10 L of the
standard solution (2) according to the above operating
conditions, the chromatogram obtained from standard
solution (2) exhibits two resolved peaks due to Iodixanol related substance II that elute before the Iodixanol
peaks and one Iodixanol related substance I peak between the two principal Iodixanol peaks. The area of
the two Iodixanol related substance II peaks is between
0.075% and 0.125% of the total area. Disregard any
peak due to the solvent front and any peak corresponding to those obtained from the blank solution.
times with 10 L of the standard solution (2) according
to the above operating conditions, the relative standard
deviation of sum of areas of two isomer peaks obtained
from Iodixanol related substance II is not more than 5%.
Measure the height of the Iodixanol related substance I
peak, and adjust the sensitivity of the amplfier to obtain
a peak height between 80% and 100% of the full scale.
Measure the height, A, above the baseline of the Iodixanol related substance I peak and the height, B, above
the baseline of the lowest part of the curve separating
this peak from the first principal Iodixanol peak: A is
not less than 1.3B. Perform the test with 10 L of the
control solution according to the above operating conditions: the peak of Iodixanol related substance I measurable.
() Dissolve an accurately weighed quantity of
Iodixanol, equivalent to about 0.125 g of anhydrous
Iodixanol, in water to make exactly 50 mL, and use this
solution as the test solution. Quantitatively dissolve an
accurately weighed quantity of Iodixanol RS, equivalent to about 0.125 g of anhydrous Iodixanol, in water
to make 10 mL, and use this solution as the standard
stock solution (1). Weigh accurately quantity of Iodixanol related substance II RS, equivqlent to about 0.125
g of anhydrous Iodixanol, dissolve in water to make
exactly 100 mL, add water to 2.0 mL of this solution to
make exactly 100 mL, and use this solution as the standard stock solution (2). Quantitatively dissolve an accurately weighed about 25 mg of Iodixanol related substance VI RS in water to make exactly 10 mL, and use
this solution as the standard solution (3). Pipet 2.0 mL

of standard stock solution (1), add water to make exactly 10 mL, and use this solution as the standard solution
(1). Pipet 5.0 mL of the standard stock solution (1) and
2.5 mL of the standard stock solution (2), add water to
make exactly 25 mL, and use this solution as the standard solution (2). Pipet 1.0 mL of standard solution (1)
and 1.0 mL of standard stock solution (3), add water to
make 3.0 mL, and use this solution as the standard solution (3). Use water as the blank solution. Perform the
test with 10 L each of the test solution, the standard
solution (1), the standard solution (2) and the standard
solution (3) as directed under the Liquid Chromatography according to the following operating conditions.
Inject 3 times repeatly for the standard solution (2).
Compare the retention times of the peaks obtained from
the standard solution (3) to those obtained from the test
solution. Iodixanol related substance VI exhibits two
peaks, the second of which may partly overlap with
another peak, and use only the area of the first and
larger peak, corresponding to about 60% of the total
area of Iodixanol related substance VI. Draw baseline
at the height of the baseline obtained from the blank solution. Calculate the area percent of Iodixanol related
substance VI, {5-[[3-[[3-[[2,3-dihydroxypropyl)amino]
carbonyl]-5-[[amino]carbonyl]-2,4,6-triiodphenyl]
(acetylimino]-2-hydroxypropyl]-(acetylimino)]-N,N'bis(2,3-dihydroxypropyl)-2,4,6-triiod-1,3-benzenedicar
boxide}, by dividing the area obtained from the test solution 0.6 is not more than 0.3%. Calculate the amount
of the related substance VII shown as a single peak,
with a shoulder, on the tail of the Iodixanol peak is not
more than 0.6%.
Detector: An ultraviolet absorption photometry
monomolecular layer aminopropylsilanized silica gel
for the liquid chromatography (5 m particle diameter).
Mobile phase: Adjust with mobile phase A and
mobile phase B according to step-wise or the slope of
concentration as follows..
mobile phase A - Acetonitrile
mobile phase B - Water
Time
(minute)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
85
15
0 ~ 25
85 66
15 34
Elution condition
solvent equilibrium
(about 20 minute)
slope

System suitability
with 10 L of the standard solution (1) according to the
above operating conditions: the chromatogram obtained

from standard solution (1) exhibits three principal unresolved peaks,the relative peak areas are about 62%,
35% and 3%; and the retention time of the last Iodixanol peak is not more than 14 minutes. When the procedure is run 10 L of the standard solution (2) according to the above operating conditions: the chromatogram obtained from standard solution (2) exhibits two
partially unresolved peaks due to Iodixanol related substance II with relative retention times of about 0.33 and
0.39, the peak area of Iodixanol related substance II is
between 0.075% and 0.125% of the total area. When
the procedure is run with 10 L of the standard solution
(3) according to the above operating conditions: the
chromatogram obtained from standard solution (3) exhibits two unresolved peaks due to Iodixanol related
compound E, with relative retention times of about 0.67
and 0.72. The resolution, between the first peak of
Iodixanol related substance VI and the first principal
peak of Iodixanol is not less than 5.0.
times with 10 L of standard solution (2) according to
the above conditions: the relative standard deviation of
total peak areas of two isomers of the related substance
II is not more than 5%.
Microbial Limit Its total viable aeronic microbial
count does not exceed 100 per mL.
Water Not more than 4.0% (0.5 g, volumetric titration, direct titration)
Assay Weigh accurately about 0.5 g of Iodixanol, add
25 mL of a sodium hydroxide solution (1 in 20) and 0.5
g of powdered zinc, connect the flask to a reflux condenser, and reflux for 1 hour. Cool the flask to room
temperature, and wash the condenser with 20 mL of
water, combine the washing with the reaction mixture,
filter. Wash the flask and the filter with several small
portions of water, filter, and add the filtered washings
to the filterate. Add 5 mL of glacial acetic acid, and titrate with 0.1 mol/L silver nitrate VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
Each mL of 0.1 N silver nitrate

= 25.84 mg of C35H44I6N6O15.
Packaing and Storage
containers.
Light-resistant, well-closed
Iodoform is freely soluble in ether, sparingly soluble in

ethanol, and practically insoluble in water.
Iodoform is slightly volatile at ordinary temperature.
Melting pointAbout 120 o C (with decomposition).
Identification Heat 0.1 g of Iodoform: a purple gas is
evolved.
Purity
(1) Water-soluble colored substances and
acidity or alkalinityShake well 2.0 g of Iodoform,

previously powdered, with 5 mL of water for 1 minute,
allow to stand and filter the supernatant liquid: the filtrate is colorless and neutral.
(2) ChlorideShake well 3.0 g of Iodoform, previously powdered, with 75 mL of water for 1 minute,
allow to stand and filter the supernatant liquid. Take 25
mL of the filtrate, add 6 mL of dilute nitric acid and
water to make 50 mL and perform the test with this solution as the test solution. Prepare the control solution
more than 0.011%).
(3) SulfateTo 25 mL of the filtrate obtained in
(2), add 1 mL of dilute hydrochloric acid and water to
make 50 mL and perform the test with this solution as
0.017%).
Loss on Drying Not more than 0.5% (1 g, silica gel,
24 hours).
Assay Weigh accurately about 0.2 g of Iodoform,
previously dried, in a glass-stoppered flask and dissolve
in 20 mL of ethanol. Add exactly 30 mL of 0.1 mol/L
silver nitrate VS and 10 mL of nitric acid, stopper the
flask, shake well and allow to stand in a dark place over
16 hours. Add 150 mL of water and titrate the excess
silver nitrate with 0.1 mol/L ammonium thiocyanate
VS (indicator: 5 mL of ferric ammonium sulfate TS).
correction.

= 13.124 mg of CHI3
tight containers.
Iodoform
CHI3: 393.73
Iodoform, when dried, contains not less than 99.0% and
not more than 101.0% of iodoform (CHI3).
Description Iodoform is a lustrous, yellow crystal or
crystalline powder. Iodoform has a characteristic odor.
KP 9 519
Iohexol
OH
H
N
OH
I
OH
H
N
HO
OH
N
I
HO
H3C
C19H26I3N3O9 : 821.14
Iohexol contains not less than 98.0% and not more than
102.0% of iohexol (C19H26I3N3O9), calculated on the
anhydrous basis.
Description Iohexol is a white or off-white powder
and is odorless.
Iohexol is freely soluble in water and in methanol, and
practically insoluble in ether or in chloroform.
Iohexol is hygroscopic.
Identification (1) Heat about 0.5 g in a crucible: violet vapors are evolved.
Iohexol and Iohexol RS (1 in 100000) as directed under
exhibit a maximum and a minimum of absorption at the
same wavelengths.
(3) Determine the infrared spectra of Iohexol and
Iohexol RS as directed in the potassium bromide disk
method under the Infrared Spectrometry: both spectra
(4) Weigh 0.1 g each of Iohexol and Iohexol RS,
dissolve in 10 mL of methanol, and use these solutions
as the test solution and the standard solution. Perform
the test with these solutions as directed under the Thin-
layer Chromatography. Spots 10 L each of the test

solution and the standard solution a silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of n-butanol, water and glacial acetic acid (50 : 25 : 11) to a distance of about 15
cm, and air-dry the plates. Examine under ultraviolet
(254 nm): the presence of exo- and endo- isomers in the
test solution and the standard solution is shown by the
appearance of two spots, each of which correspond to
the corresponding principal spot. The Rf values obtained from the test solution and the standard solution
are the same.
D : between -0.5 and
+0.5 C (0.5 g, water 10 mL and 100 mL).
Purity (1) Clarity and color of solutionWeigh

16.18 g of Iohexol, dissolve in water, to make exactly
25 mL, filter through a filter membrane having a porosity of 0.22 m. Determine the absorbanas of this filterate as directed under the Ultraviolet-visible Spectrophotometry and using water as the blank, determine the
absorbances of this solution at 400, 420 and 450 nm are
not more than than 0.180, 0.030, and 0.015, respectively.
(2) Heavy metals Proceed with 1.0 g of Iohexol
according to Method 1 and perform the test. Preare the
(3) Free aromatic amine Transfer 0.2 g of
Iohexol to a 50-mL volumetric flask, add 15 mL of water, and mix to dissolve. To a second 50-mL volumetric
flask, add 5 mL of water and 10 mL of a solution containing 10 g per mL by dissolving Iohexol related
substance 1 {5-(amino)-N,N,-bis(2,3-dihydroxypropyl)2,4,6-triiod-1,3-benzenedicarboxyamide)} RS in water.
To a third 50-mL volumetric flask, add 15 mL of water.
Place these solutions in an ice bath, and cool for 5 minutes. Add 3.0 mL each of 5 mol/L hydrochloric acid
TS and swirl to mix. Add 2.0 mL of sodium nitrite solution (1 in 50) and allow to stand for 4 minutes. Add
2.0 mL each of sulfamic acd solution (1 in 25), shake,
and allow to stand for 1 minute. Remove these solutions from the ice bath. To each flask, add 2 mL each,
of a solution of N-(1-naphthyl)ehtylenediamine dihydrochloride in dilute propylene glycol (7 in 10) (1 in
1000), mix, add water to make 50 mL, allow to stand
for 5 minutes, and use these solutions as test solution,
standard solution and blank solution. Perform the test
with these solutions as the directed under Ultravioletvisible spectrophotometry: the absorbance of the test
solution is not larger than the absorbance of the standard solution (not more than 0.05%).
(4) Free iodineTransfer 2.1 g of Iohexol to a 50mL centrifuge tube with a stopper, add about 20 mL of
water, and shake vigorously to dissolve. Add 5 mL of
toluene and 5 mL of 1 mol/L sulfuric acid TS, shake,
and centrifuge at high speed: the toluene layer shows
no red or pink color.
(5) Free iodideWeigh 5.0 g of Iohexol, dissolve
in about 20 mL of water, transfer to a centrifuge tube
with a stopper, add 20 mL of water, and shake vigorously or heating weakly to dissolve, and titrate with
0.001 mol/L silver nitrate VS (potentiometric titration,
blank determination, and make any necessary correction (0.001%).
Each mL of 0.001 mol/L AgNO3 = 126.9 g of I

(6) Ionic substancesRinse all glassware 5 times
with distilled water. Determine the specific resistance,
( RSP ), at 20 with a solution of Iohexol (1 in 50),
calculate the specific conductance, k, taken by the formula: this specific conductance is not larger than the
conductance of 0.0002% sodium chloride (not more

than 0.01%).
Specific conductance =
butanol in water containing about 0.05 mg per each mL.

1
106
R SP
(7) Methanol, isopropanol, methoxy ethanol

Transfer about 6.25 g of Iohexenol exactly weighed,
add 5 mL of the internal standard solution, add water to
make 25 mL, and use this solution as the test solution
(1). Transfer 5.0 mL of the test solution (1) and 1 mL
of water to a vial with gum stopper. Heat the sealed vial
at 95 for 15 minutes, use this solution as the test solution (2). Transfer 5.0 mL of the test solution (1) and 1
mL of s the tandard solution (2) to a vial with gum
stopper. Heat the sealed vial at 95 C for 15 minutes,
and use this solution as the test solution (3). Transfer
5.0 mL of t the test solution (1) and 1.0 mL of the standard solution (3) to a vial with gum stopper. Heat the
sealed vial at 95 C for 15 minutes, and use this solution as the test solution (4). Transfer 5.0 mL of the test
solution (1) and 1.0 mL of the standard solution (4) to a
vial with gum stopper. Heat the sealed vial at 95 C for
15 minutes, and use this solution as the test solution (5).
Separately, transfer about 0.6 g of methanol accurately
weighed, add about 100 mL of water, mix, add about
0.6 g of methoxy ethanol in this solution, and mix, add
water to make 1000 mL, and use this solution as the
standard solution (1). Pipet about 10.0 mL of standard
solution (1), add water to make exactly 50 mL, pipet
10.0 mL of this solution, add water to make 100 mL,
about 5.0 mL of standard solution (1), add water to
make exactly 100 mL, and use this solution as the standard solution (3). Add water in 10.0 mL of standard solution (1) to make exactly 100 mL, and use this solution as the standard solution (4). Add water in 10.0 mL
of the standard solution (4) and 10.0 mL of the internal
standard solution to make exactly 50 mL, transfer 6.0
mL of this solution to a vial fitted with a septum and
crimp cap, and seal, heat the sealed vial at 95 C for 15
minutes, and use this solution as the standard solution
(5). Perform the test with 2 mL each of the test solution
(2), the test solution (3), the test solution (4), the test
solution (5) and the standard solution (5) as directed
under the Gas Chromatography according to the following operating conditions using the injection port
apparatus for the headspace, calculate the peak areas of
the principal peak from each chromatograms. Plot the
peak area ratios obtained from the test solutions against
the quatity of amount of methanol, amount of isopropanol and amount of methoxyethanol added per g of
Iohexol. Extrapolate the line joining the points until it
intercepts the concentration axis. The distance between
this point and the intersection of the axis is the amount
(mg/g) of methanol, isopropanol and methoxyethanol.
Amounts (mg/g) of methanol and isopropanol are not
more than 0.005%, respectively, the amount of methoxyethanol is not more than 0.002%.
Internal standard solutionPrepare a solution of 2-
Detector : A hydrogen flame-ionization detector
Column : About 0.53 mm in inside diameter and 30
m in length fused silica capillary column bonded with a
3 m layer of 6% cyanopropylphenyl and 94% dimethylpolysiloxane.
Column temperature : It is held at 40 C for 5 minutes and is programmed to increase at a rate of 10 C
per minute to 100 C, maintain at 100 for 1 minute.
Carrier gas : helium
Flow rate : 14 mL/minute
Inject port temperature : 140 C
Detector temperature : 250 C
System suitability
with standard solution (5) according to the above operating conditions, the relative retention times of methanol, isopropanol, 2-butanol and methoxy ethanol are
about 0.3, 0.5, 1.0 and 1.3, respectively, with the resolution between methanol peak and isopropanol peak being not less than 2.5.
times with standard solution (5) according to the above
each peak area is not more than 5%.
(8) 3-chloro-1,2-propanediol Dissolve about 1 g
of Iohexol, accurately weighed, in 1.0 mL of water, extract 4 times with 2 mL of ethyl acetate, and combine
the extracts. Dry the combined extracts with anhydrous
sodium sulfate. Filter, and wash the filter with a small
amount of ethyl acetate. Combine the wash with the filtrate, and concentrate to the volume of 2.0 mL, using a
warm water bath and a stream of nitrogen. Pass this solution through a membrane filter, and use the clear filtrate as the the test solution. Separatry, dissolve an accurately weighed quantity of 3-chloro-1,2-propanediol
quantitatively in ethyl acetate to obtain the solution
having a known concentration of about 20 g per mL,
the test with about 2 L each of the test solution and
the standard solution as directed under the Gas Chromatography according to the following operating conditions: 3-chloro-1,2-propanediol, a mixture of two
isomers, exhibits two principal peaks at 12 and 12.5
minutes, respectively. Measure the sums of two peak
areas obtained from 3-chloro-1,2-propanediol, AST
and ASA , calculate the amount of 3-chloro-1,2propanediol (not more than 0.0025 %).
Amount (g ) of 3-chloro-1,2-propanediol
= 100
AST 2CST
ASA
R
CST : Concentration (g/mL) of 3-chloro-1,2propanediol in the standard solution.

R : The recovery ratio (%) measured in the system
KP 9 521
suitability test.
Detector : A hydrogen flame-ionization detector.
Column : A about 0.32 mm in inside diameter and
about 30 m fused-silica capillary column bonded with a
1 m layer of phase G46 with 14 % cyanopropylphenyl-86 % methylpolysiloxane.
Column temperature : At first, allow to stand at 50
C for 2 minutes and is programmed to increase at a
rate of 10 C per minute to 200 C.
Injection port temperature : About 230 C
Detector temperature : About 250 C
System suitability
with system suitability solution according to the above
operating conditions, the recovery rate of 3-chloro-1,2propanediol obtained from iohexanol is between 60 and
90 %.
Recovery rate (%) of 3-chloro-1,2-propanediol
= 100 ARC CST
AST
C RS
CRS: Concentration (g/mL) of 3-chloro-1,2propanediol obtained from the system suitability solution.
CST : Concentration (g/mL) of 3-chloro-1,2propanediol obtained from the standard solution.
ARC : Peak area of 3-chloro-1,2-propanediol obtained
from the system suitability solution.
AST : Peak area of 3-chloro-1,2-propanediol obtained
times with the standard solution according to the above
condotions: the relative standard deviation is not more
than 10 %.
System suitability solution: Dissolve 1 g of
Iohexol containing less than 5 g of chloropropanediol
in 1 mL of water. Quantitatively dissolve an accurately
weighed quantity of 3-chloro-1,2-propanediol in ethyl
acetate to obtain a solution having a concentration of
about 25 g per mL, Add 2.0 mL of ethyl acet ate solution to the aqueous solution of Iohexol in a separator,
amd mix. Transfer the ethyl acetate layer to a separate
containers, and extract the aqueous layer three additional times with 2 mL of ethyl acetate, combining all
four extracts. Dry the combined extracts using anhydrous sodium sulfate, filter, and wash the filter with a
small amount of ethyl acetate. combine the wash, concentrate to 2.0 mL under nitrgen stream, filter with
membrane filter, and use the filterate as the system suitability solution.
(9) Related substancesWeigh accurately 75 mg
of Iohexol, add water, dissolve to make 50 mL, and use
this solution as the test solution. Perform the test with
10 L of this solution as directed under the Liquid

conditions, and determine the amount of each the related substances: the peaks other than the principal
peak are not more than 0.1%, respectively, the peaks of
O-alkylated substances are not more than 0.6 %, the
sum of all the related substances other than O-alkylated
substances is not more than 0.3%.
Amount (%) of the related substance = 100
Ai
AS
Ai : Each peak area other than the principal peak

A s : Sum of the area of all peaks
Detector : An ultraviolet absorption Photometer
(wavelength: 254 nm)
(3 m to 10 m in particle size diameter).
Mobile phase : Change the rate of acetonitrile and
water, the chromatograph is programmed to provide variable mixtures of these solvents, the percentage of acetonitrile increases from 1% to 13% at an increase rate
of 0.2% per minute.
System suitability
with 10 L of system suitability solution according to
the above conditions, the relative retention time for the
O-alkylated substances is between 1.1 and 1.4 to 1.0 of
the retention time for the exo-isomer of iohexol with
the resolution between iohexol related substance II and
iohexol related substance III being not less than 20.0,
and the peak rea of iohexol related substance III is
0.5 % 0.1 % by comparison to the total area of all
of the peaks in the chromatogram.
System suitability solutionDissolve acculately
weighed quantities of Iohexol RS, Iohexol related substance I RS, and Iohexol related substance III RS in
water to obtain a solution having known concentrations
of about 1.5, 0.0075 and 0.0069 mg per mL, repectively,
and use this solution as the system suitability solution.
Assay Weigh accurately about 0.5 g of Iohexol, add
25 mL of 1.25 mol/L sodium hydroxide TS and 0.5 g of
powdered zinc, connect the flask to a reflux condenser,
and reflux the mixture for 1 hour. Cool the flask to
room temperature, rinse the condenser with 20 mL of
water, add the washing in the reaction mixture, mix,
and filter the mixture. Rinse the flask and the filter
throughly with small portions of water, sum the rinsings to the filtrate. Add 5 mL of glacial acetic acid, and

titrate with 0.1 mol/L silver nitrate VS (potentiometric
titration, Endpoint Detection Method in Titrimetry).
Each mL of 0.1 mol/L silver nitrate
= 27.37 mg of C19H26I3N3O9

Iopamidol
HO
OH
NH
O
H
N
HO
N
H
H
OH
fate (1 in 10), shake well, allow to stand for 1 minute,

and add 1 mL of naphthylethylenediamine TS and water to make exactly 50 mL. Determine the absorbance
of this solution at 495 nm as directed under Ultravioletvisible Spectrophotometry using a solution, prepared in
the same manner without Iopamidol, as the blank: the
absorbance is not more than 0.12 (not more than
0.020%).
(3) Iodine Dissolve 2.0 g of Iopamidol in 25 mL
of water, add 5 mL of 1 mol/L sulfuric acid and 5 mL
of toluene, shake well, and allow to stand:the toluene
layer is colorless.
(4) Free iodine ion Weigh accurately about 5.0
g of Iopamidol, dissolve in 70 mL of water, and adjust
the pH to about 4.5 with dilute acetic acid . To this solution add 2 mL of 0.1 mol/L sodium chloride TS, and
titratewith 0.001 mol/L silver nitrate VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
Content of iodine ion in Iopamidol is not more than
0.001%
OH
I
O
OH

= 0.1269 mg of I

436 nm : Between 4.6
and 5.2 (after drying, 4 g, water, warm, after cooling,
10 mL, 100 mm).
(5) Heavy metalsMoisten 1.0 g of Iopamidol

with a small quantity of sulfuric acid, heat gradually to
almost incinerate by a possibly lower temperature. After cooling, moisten again with a small quantity of sulfuric acid, heat gradually until white fumes no longer
are evolved, and incinerate by ignition 450 to 550 C.
Proceed as directed in Method 2, and perform the test.
Prepare the control solution with 1.0 mL of Standard
(6) Related substancesDissolve 0.10 g of Iopamidol in water to make exactly 10 mL, and use this solution as the test solution. Separately, dissolve 10 mg of
N,N-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5hydroxyacetylamino2,4,6-triiodoisophthalamide
in
water to make exactly 100 mL. Pipet 5 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with
exactly 20 L each of the test solution and standard solution as directed under Liquid Chromatography according to the following conditions, and determine each
peak area of the both solutions by the automatic integration method: each area of the peaks other than the
peak of iopamidol from the test solution is not larger
than the peak area of the standard solution, and the total
of these areas is not larger than 2.5 times of the peak
area of the standard solution.

1.0 g of Iopamidol in 10 mL of water: the solution is
clear and colorless
(2) Primary aromatic amines Dissolve 0.60 g of
Iopamidol in 8 mL of water add 1 mL of a solution of
sodium nitrite (1 in 50 ) and 12 mL of 2 mol / L hydrochloric acid TS, shake, and allow to stand for 2 minutes. Add 1 mL of a solution of ammonium amidosul-
(wavelength; 240 nm).
C17H22I3N3O8 : 777.09
Iopamidol, when dried, contains not less than 99.0%
and not more the 101.0% of iopamidol ( C17H22I3N3O8).
Description Iopamidol is a white, crystalline powder.
Iopamidol is very soluble in water, sparingly soluble in
methanol, and very slightly soluble in dehydrated ethanol.
Identifiation (1) To 0.05 g of Iopamidol add 5 mL of
hydrochloric acid, heat for 10 minutes in a water bath:
the test solution responds to the Qualitative Tests for
(2) Heat 0.1 g of Iopamidol over a flame: a purple
gas is evolved.
(3) Determine the infrared absorption spectrum of
Iopamidol and Iopamidol RS, previously dried, as directed in the potassium bromide disk method under
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
KP 9 523
about 35C.
Mobile phase: Use water as the mobile phase A,
and a mixture of water and methanol (3:1) as the mobile phase B. Change the mixed ratios of the mobile
phase A and mobile phase B stepwise as follows:
Iopanoic Acid
COOH
CH2CC2H5
Time (minute)
0~6
6 ~ 18
18 ~ 30
30 ~ 34
Mobile phase A
(vol%)
92
92 65
65 8
8
Mobile phase B
(vol%)
8
8 35
35 92
92
Flow rate:Adjust the flow rate to 1.5 mL per minute.

long as the retention time of iopamidol.
System suitability
System performance: Dissolve 1 mL of the test
solution and 10 mg of N,Nbis[2-hydroxy-1(hydroxymethyl)ethyl]-5-hydroxyacetylamino-2,4,6triiodoisophthalamide in water to make 100 mL. When
the procedure is run with 20 L of this solution under
the above operating conditions, N,Nbis[2-hydroxy-1(hydroxymethyl)ethyl]-5-hydroxyacetylamino-2,4,6triiodoisophthalamide and iopamidol are eluted in this
less than 7.
above operating conditions, the relative standard deviation of the peak areas of N,Nbis[2-hydroxy-1(hydroxymethyl)ethyl]-5-hydroxyacetylamino-2,4,6triiodoisophthalamide is not more than 1.0%.
Loss on Drying Not more than 0.3% (1 g, 105C, 3
hours).
Assay Weigh accurately about 0.5 g of Iopamidol,
previousiy dried, transfer to a saponification flask, dissolve in 40 mL of sodium hydroxide TS, add 1 g of
zinc powder, boil for 30 minutes under a reflux confenser, cool, and filter. Wash the flask and the filter paper with 50 mL of water, and combine the washing
with the filtrate. Add 5 mL of acetic acid (100) to this
solution, and titrate with 0.1 mol/L silver nitrate VS
Titrimetry).

= 25.90 mg of C17H22I3N3O8
Packaging and Storage Light-resistant, well-closed
containers.
NH2
I
C11Hl2I3NO2: 570.93
Iopanoic Acid, when dried, contains not less than
97.0% and not more than 101.0% of iopanoic acid
(C11Hl2I3NO2).
Description Iopanoic Acid is a pale yellowish white,
crystalline powder and has a flint, characteristic odor.
Iopanoic Acid is soluble in ethanol or in acetone, sparingly soluble in glacial acetic acid or in ether and practically insoluble in water.
Iopanoic Acid dissolves in sodium hydroxide TS.
Iopanoic Acid is gradually colored by light.
Identification Mix about 100 mg of Iopanoic acid
with 500 mg of sodium carbonate in a crucible, and
heat until thoroughly charred. Cool, add 5 ml of hot
water, heat on a steam bath for 5 minutes, and filter: the
solution responds to the tests for Iodide
Melting Point
composition).
Purity (1) Soluble halidesTransfer 0.5 g of Iopanoic Acid to the stoppered cylinder, add 10 mL of 2
mol/L nitric acid and 15 mL of water, mix stirring for 5
minutes, filter with filter pater, perform the test with 10
mL of the filtrate as the test solution according to the
Chloride Limit test, this solution is not dark than the
Control solution Take 0.1 mL of 0.01 mol.L hydrochloric acid and 6 mL of dilute nitric acid, and mix.
Add water to this solution to make 10 mL.
(2) Free iodineDissolve 0.20 g of Iopanoic Acid
in 2.0 mL of distilled water and 2.0 mL of chloroform,
and allow to stand for 1 minute with shaking, The chloroform layer exhibit not purple color..
(3) Heavy metalsProceed with 1.0 g of Iopanoic
Acid according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
hours).
Assay Weigh accurately about 0.25 g of lopanoic Acid, previously dried, and add 0.5 g of zinc powder and

30 mL of sodium hydroxide TS. Boil for 30 minutes
with a reflux condenser, add 20 mL of water through
the condenser and filter through absorbent cotton.
Wash the flask and filter with a little volume of water
and combine the filtrate and washings. After cooling,
add 5 mL of acetic acid anhydride, and titrate with 0.05
mol/L silver nitrate VS until the color of the precipitate
changes from yellow to green (indicator: 1 mL of tetrabromophenol-phthalein ethyl ester TS).
trate with 0.1 mol/L sodium hydroxide VS.

= 57.09 mg of C11Hl2I3NO2
tight containers.
Iophendylate

= 9.516 mg of C11Hl2I3NO2
tight containers.
H
I
C(CH 2)8COOC 2H5

CH 3
and enantiomer
C19H29IO2: 416.34
Iopanoic Acid Tablets

Iopanoic Acid Tablets contain not less than 95.0% and
not more than 105.0% of the labeled amount of iopanoic acid (C11Hl2I3NO2: 570.93).
Tablets, with Iopanoic Acid.
Identification Triturate a quantity of finely powdered
Tablets, equivalent to about 1 g of Iopanoic Acid, with
two 10 mL portions of hexane, and decant and discard
the liquid. Allow the residue to dry spontaneously, triturate with 15 mL of acetone, and filter. Repeat the trituration with another 15 mL portion of acetone, evaporate the combined filtrates on a steam bath to a volume
of not more than 1 mL, add, with constant stirring, 20
mL of water, filter, wash the precipitate with two 5 mL
portions of water, and dry at 105 C for 2 hour: the
Iopanoic Acid so obtained melts between 150 C and
158 C, with decomposition, and responds to the Identification test of Iopanoic Acid.
Purity Soluble halidesPrepare the powder of Iopanoic Acid Tablet, equivalent to 0.5 g of Iopanoic Acid
according to the labeled amount, proceed as directed in
the Purity(1) of Iopanoic Acid.
Iophenylate, a mixture of isomers of ethyl iodophenylundecanoate, consists of ethyl 10-(iodophenyl) undecanoate and contains not less than 98.0% and not more
than 102.0% of iophenylate (C19H29IO2).
Description Iophendylate is a colorless or pale yellow colored syrupy liquid and is odorless or has etherlike odor.
Iophendylate is freely soluble in ethanol, in benzene, in
chloroform or in ether and slightly soluble in water.
Iophendylate is gradually colored in the air.
Identification Place about 1 mL of Iophendylate, 15
mL of water and 7 g of potassium dichromate in a
round-bottom flask. Carefully add 10 mL of sulfuric acid, moderating the vigorous reaction by cooling the
flask with tap water. When the reaction has subsided,
reflux the mixture for 2 hours. After cooling, pour the
contents of the flask into the 25 mL of water, filter the
mixture with suction and wash the precipitate with a
small quantity of cold water. Crystallize the precipitate
from 10 mL of diluted alcohol: the sublimate of piodobenzoic acid melts between 268 C and 272 C.
Refractive Index
nD20 : Between 1.524 and 1.526.

Disintegration Test Not more than 30 minutes.
Uniformity of Dosage Units
ment.

Iopanoic Acid Tablets. Weigh accurately a portion of
the powder, equivalent to about 1 g of iopanoic acid
(C11Hl2I3NO2), and add 10 mL of hexane, triturate and
filter. Repeat the same procedure, then add the neutralized ethanol to residue, warm to 70 o C and filter.
Wash four times the residue with 10 mL of neutralized
ethanol, cool combined filtrate and washings, to room
temperature, add 3 ~ 5 drops of thymol blue TS and ti-
Specific Gravity
20
: Between 1.248 and 1.257.
d 20
Purity (1) Free acidTransfer about 4 g of Iophendylate, accurately weighed, to a small flask, add 20 mL
of alcohol and dissolve. Add 5 drops of phenolphthalein TS and titrate with 0.05 mol/L alcoholic potassium
hydroxide VS to a pink color that persists for 30
seconds: not more than 0.60 mL of 0.05 mol/L alcoholic potassium hydroxide VS is required for neutralization. Perform the blank determination and make any
necessary correction (not more than 0.3% as iophenylundecanoic acid).
(2) Free iodineDetermine absorbance of Iophen-
KP 9 525
dylate in a 40 mm cell, at a 485 nm, as directed in the
Ultraviolet-visible Spectrophotometry, using water as
the blank: the absorbance is not greater than 0.16 (not
more than 7.5 ppm).
(2) under Iophendylate.


Assay Dissolve about 50 mg of Iophendylate, accurately weighed, in 5 mL of toluene contained in a suitable separatory funnel. Add 15 mL of sodium biphenyl
and shake vigorously for 2 minutes. Extract with three
10 mL volumes of 5 mol/L phosphoric acid. Combine
the lower phases and add 1 mol/L sodium hypochlorite
TS drop-wise until the solution turns brown. Add an
additional 0.5 mL of 1 mol/L sodium hypochlorite TS
and shake for 3 minutes. Add 5 mL of saturated phenol
solution, freshly prepared and stand for 1 minutes, accurately timed. Add 1 g of potassium iodide, shake 30
seconds and titrate rapidly with 0.1 mol/L sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint
is approached.

= 6.939 mg of C19H29IO2
tight Containers.

Iophendylate.
Foreign insoluble Matter Test It meets the requirement.
Assay Proceed as directed in the Assay under Iophendylate.
tight containers.
Iopromide
OH
CH3
O
Iophendylate Injection
Iophendylate Injection contains not less than 98.0 %

and not more than 102.0% of the iophendylate
(C19H29IO2: 416.34).
OH
H
N
H3CO
Description Iophendylate Injection is colorless or

pale yellow colored syrupy liquid, is odorless or has
ether-like odor.
Iophendylate Injection is freely soluble in ethanol, in
benzene, in chloroform or in ether and very slightly soluble in water.
Iophendylate Injection is gradually colored in the air.
Identification Proceed as directed in the Identification under Iophendylate.
Refractive Index
nD20 : Between 1.524 and 1.526.

Specific Gravity
20
: Between 1.248 and 1.257.
d 20
Purity (1) Free acid Proceed as directed in the Purity (1) under Iophendylate.
(2) Free iodine Proceed as directed in the Purity
OH
N
H
I

the Injections, with Iophendylate.
OH
C18H24I3N3O8 : 791.11
Iopromide contains not less than 97.0% and not more
than 102.5% of iopromide (C18H24I3N3O8), calculated
on the anhydrous and solvent-free basis.
Description White to slightly yellow powder.
Iopromide is freely soluble in water and in dimethylsulfoxide, and practically insoluble in acetone, in ethanol
or in ether.
Iopromide and Iopromide RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) Perform the test with Iopromide according to
the related substances under the Purity: the principal
sports obtained from the test solution and the standard
solution show the same Rf values.
Purity (1) Heavy metalsWeigh about 1.0 g of Iopromide, dissolve in water to make exactly 20 mL. Add

2.0 mL of pH 3.5 Acetate buffer to 12.0 mL of this solution, and use this solution as the test solution. Separately, pipet 1.0 mL of standard lead solution, add 9.0
mL of water, 2.0 mL of the test solution and 2.0 mL of
acetic acidammonium acetate buffer, and use this solution as the standard solution. Add 5 mL of water to 15
mL of 1 mol/L sodium hydroxide, mix, and add 20 mL
of glycerin. Pipet each 1.0 mL of this solution and each
0.2 mL of 4% thioacetamide TS into two nessler tube,
and heat in water bath for 20 seconds. Immediately add
the test solution and standard solution to each solution,
allow to stand for 2 minutes, and view downward over
a white surface: the color of the solution from the test
solution is not darker than that of the solution from the
standard solution (Not more than 20 ppm).
pH 3.5 acetic acidammonium acetate bufferDissolve 25.0 g of ammonium acetate in 25 mL of
water, add 38.0 mL of 6 mol/L hydrochloric acid TS,
and mix. If necessary, add 6 mol/L ammonia TS or 6
mol/L hydrochloric acid TS to adjust a pH 3.5, and add
water to make exactly 100 mL.
(2) Free iodineWeigh 2.0 g of Iopromide, and
dissolve in 20 mL of water. Add 2 mL of toluene and 2
mL of diluted surfuric acid, and shake vigorously: the
toluene layer shows no red color.
(3) Free iodideWeigh 10.0 g of Iopromide, and
dissolve in 70 mL of water. Adjust with 0.05 mol/L
surfuric acid VS to a pH of 3.5 0.5, titrate with
0.001 mol/L silve nitrate VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). Perform the
blank determination and make any necessary correction
= 126.9 g of I.
(4) Free aromatic amineTransfer 0.5 g of Iopromide to a 25-mL volumetric flask, add 20 mL of
water, and dissolve, and use this solution as the test solution. Dissolve a suitable quantity of Iopromide related
substance I RS in water, and dilute with water to make
exactly 100 mL. Transfer 2.0 mL of this solution to a
25-mL volumetric flask, add 18.0 mL of water, and mix,
and use this solution as the standard solution. Transfer
20 mL of water to a 25-mL volumetric flask, and use
this solution as the blank solution. Place the flasks in an
ice bath, and protect from light. Add slowly 1.0 mL of
8 mol/L hydrochloric acid TS, mix, and allow to stand
for 5 minutes. Add 1.0 mL of sodium nitrite solution (1
in 50), mix, and allow to stand for 5 minutes. Add 0.50
mL of freshly prepared sulfamic acid solution, (8 in
100). Shake each flask vigorously several times within
the next 5 minutes, venting off the gas that evolves.
Add 1.0 mL of freshly prepared solution of N-(1naphthyl)ethylenediamine dihydrochloride in a mixture
of propylene glycol and water (70:30) (1 in 1000), and
shake. Remove the flasks from the ice bath, and allow
to stand in a water bath at about 25 for 10 minutes.

Dilute with water to make exactly 25 mL, and degas
with the aid of sonication for 1 minute. Perform the test
with these solutions as directed under the Ultravioletvisible Spectrophotometry. Determine the absorbances,
AT and AS , of the test solution and the standard solution at the wavelength maximum absorbance at about
495 nm using the blank solution. Calculate the percentage of aromatic amine in the portion of Iopromide taken by the following formula: it is not more than 0.10%.
The absorbance of the standard solution is not less than
0.40.
= 10
WS AU
W U WS
WS : The quantity, in mg, of Iopromide related substance I RS taken to prepare the standard solution.
WU : The quantity, in mg, of the Iopromide taken to
prepare the test solution.
(5) EthanolDissolve an exactly weighed 0.5 g of

Iopromide in dimethylformamide to make exactly 10
mL, and use this solution as the test solution. Separately, weigh accurately a suitable volume of ethanol, add
dimethylformamide, mix, prepare a solution having a
known concentration of about 0.050 mg of ethanol
(C2H5OH) per mL, and use this solution as the standard
solution. Use dimethylformamide as the blank solution.
Transfer 2.0 mL each of the test solution, the standard
solution and the blank solution to separate headspace
vials, add 10 L each of 1 mol/L hydrochloric acid TS
to each vial, then seal the vials using a flanged cap.
Perform the test as directed under the Gas Chromatography according to the following operating conditions,
and determine the peak area of ethanol, AT and AS
Concentration (mg/mL) of ethanol =
C AT
I
AS
C : Concentration of Ethanol in the standard solution (mg/mL).

I : Concentration of Iopromide in the test solution
(mg/mL).
Detector : A hydrogen flame ionization detector
Column : A capillary column is about 0.25 mm in
a 1.4 m film of liquid phase 6% cyanopropylphenyl94% dimethylpolysiloxane.
Column temperature : Programmed according to the
following steps: it is held at 40 C for 10 minutes, then
increased at a rate of 5 C per minute to 70 C; it is then
increased at a rate of 30 C per minute to 220 C.
Inject port temperature : 160 C
Headspace sampler temperature : 80 C
KP 9 527
Detector temperature : maintained at 250 C.
Flow rate : 27 mm/second
System suitability
with 2.0 mL of the standard solution as directed under
the above operating conditions, the retention time of
ethanol is about 3 minutes.
times with 2.0 mL of the standard solution, the relative
standard deviation of the peak area is not more than
4.0%. When the procedure is run with the blank solution according to the above operating conditions, the
chromatogram shows no peak responses at the retention
time for alcohol.
(6) N-acetyl compound (Iopromide related compound I)Using the chromatograms obtained in the
Assay, calculate the percentage of N-acetyl compound
in the Iopromide taken by the formula:
Amount (%) of N-acetyl compound =
( A + AY2 )
W
20 B Y1
W1 ( RY1 + RY2 )
WB : Quantity, in mg, of Iopromide related substance I RS taken to prepare the related substance I
standard solution.
W1 : Quantity, in mg of Iopromide taken to prepare
the test preparation.
AY1 , AY2 : Peak responses for the Iopromide related
substance I Y1 - and Y2 -isomers, respectively, in the
chromatogram obtained from the test preparation.
RY1 , RY2 : Peak responses for the Iopromide related
substance I Y1 - and Y2 -isomers, respectively, in the
chromatogram obtained from the Related compound I
standard solution.
(7) Other related substancesDissolve about 0.1 g

of Iopromide in a mixture of methanol and water (1:1)
to make exactly 10 mL and use this solution as test solution. Separately, dissolve dilute appropriately a suitable amount of Iopromide RS in a mixture of methanol
and water (1:1) to make exactly 0.01, 0.05, 0.1 and 0.2
mg per each mL, and use this solution as the standard
solutions. Perform the test with these solutions as directed under the Thin-layer chromatography. Spot 1
L and 2 L of the test solution and 1 L of each of the
standard solutions on two separate thin-layer chromatographic plates of silica gel with fluorescent indicator
for thin-layer chromatography. Place one plate in a development chamber containing the acidic eluant, and
the second plate in a development chamber containing
the basic eluant. Develop the plates to a distance about
15 cm, remove the plates from the chambers, and airdry the plates. Both plates are exposed to UV light
(main wavelength: 254 nm). Separately, the plate developed with the acetic eluant is exposed to ammonia
vapors 10 to 30 minutes and air-dry the plates. Both

plates are exposed to UV light until the principal spots
appear yellow. Spray evenly with visusalization solution, and examine the plates under ambient light. Determine total concentration of all secondary spots, except those due to free aromatic amine and to the Nacetyl compound obtained in the test solution for limit
of N-acetyl compound, is not more than 3.0%.
Acidic eluantchloroform : methanol : water : formic acid (62 : 32 : 6 : 2)
Basic eluantdioxane : water : ethanol (85 : 15 : 4)
Visualization solutionDissolve 2.7 g of ferric chloride in a 100 mL of 2.4 mol/L hydrochloric acid, use
this solution as the solution A. Store this solution in a
refrigerator. Dissolve 3.5 g of potassium ferricyanide in
100 mL of water, use this solution as the solution B.
Store this solution in a refrigerator. Dissolve 5.0 g of
sodium arsenite in 30 mL of 1 mol/L sodium hydroxide
solution that has been cooled to 0. While stirring mix
with 65 mL of 2.4 mol/L hydrochloric acid, use this solution as the solution C, and store at room temparature.
Use the clear supernatant. Mix 10 mL of solution A, 10
mL of solution B and 2.0 mL of solution C, use this solution within 30 minutes.
(8) IsomerUsing the chromatogram obtained
from the test solution in the Assay, calculate the
amounts of E1 - and Z1 -isomers of Iopromide according to the following equation formula, is between 49.0
and 60.0%.
Amounts (%) of E1- and Z1 -isomers of Iopromide
= 100(rB1 + rZ1) /(rB1 + rB2 + rZ1 + rZ2 )
Amounts (%) of E2 - and Z2 -isomers of Iopromide
= 100(rE2 + rZ2 ) /(rE1 + rE2 + rZ1 + rZ2 )
rE1 , rE2 , rZ1 , and rZ2 : the peak areas of E1 , E 2 ,
Z1 and Z 2 - isomers of Iopromide.
Water Not less than 1.5% (1 g, volumetric titration

method, direct titration).
Assay Weigh accurately about 38 mg of Iopromide
and Iopromide RS and dissolve in a mixture of methanol and water (1 : 1) to make exactly 20 mL, and use
this solution as the test solution. Separately, weigh accurately about 38 mg of Iopromide RS (previously
measure the water), dissolve in a mixture of methanol
and water (1 : 1), to make exactly 20 mL, and use this
10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operatiing conditions and calculate the peak area of Iopromide. The test for the peak

identification of E-isomer is run as follows. Add a constant volume of standard solution to a vial, seal, heat
for 15 minutes at 121, and cool. Perform the test with
the cooled solution according to the following operating conditions, and compare with the peak of standard
solution unheated: identify with the retention time of
two isomer peaks increasing the size after heating.
Amount (mg) of iopromide (C18H24I3N3O8)
= amount (mg) of Iopromide RS AT
AS

well-closed containners.
Iotalamic Acid
COOH
I
CH3COHN
CONHCH 3
I
C : Concentration (mg/mL) of Iopromide RS in the

standard solution.
AT : Sum of peak area of E1 , E 2 , Z1 and Z 2 isomers obtained from the test solution.
AS : Sum of peak area of E1 , E 2 , Z1 and Z 2 isomers obtained from the standard solution.
(wavelength: 254 nm)
Mobile phase : Mix gently 6 g of chloroform with
59 g of methanol, then add 900 g of water, and do not
stir or sparge the mobile phase during use. Allow the
mobile phase to flow for not less than 60 minutes between each injection.
Flow rate : About 1.2 mL/minute
about 20.
System suitability
with 10 L of the standard solution as directed under
the above operating conditions, the relative retention
times for Iopromide E1 -isomer, Iopromide E 2 -isomer,
Iopromide Z1 -isomer, and Iopromide Z 2 -isomer are
about 0.70, 0.75, 0.85, and 1.0, respectively with the
resolution between Iopromide isomers Z1 and Z 2
being not less than 2.0; Separately, weigh accurately
about 1.9 mg of Iopromide related substance I RS. Add
the mixture of methanol and water (1 : 1), and dissolve
to make exactly 100 mL.. When the procedure is run
with 10 L of this solution as directed under the above
operating conditions, the relative retention times of Y1 and Y2 -isomers of the Iopromide related compound I
are about 0.28 and 0.31, respectively, and the signal-tonoise ratio for Y2 -isomer peak is not less than 20.
times with 10 L of standard solution according to the
above operating conditions: the relative standard deviation of the peak areas of Iopromide is not more than
2.0%.
C11H9I3N2O4: 613.91
Iotalamic Acid, when dried, contains not less than
99.0% and not more than 101.0% of iotalamic acid
(C11H9I3N2O4).
Description Iotalamic Acid is a white powder and is
odorless.
Iotalamic Acid sparingly soluble in ethanol, very
slightly soluble in water and practically insoluble in
ether.
Iotalamic Acid dissolves in sodium hydroxide TS.
Iotalamic Acid is gradually colored by light.
Identification (1) Heat 0.1 g of Iotalamic Acid over a
flame: a purple gas is evolved.
(2) Determine the infrared spectra of Iotalamic Acid and Iotalamic Acid RS, previously dried, as directed
in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
2.0 g of Iotalamic Acid in 10 mL of sodium hydroxide
TS: the solution is clear and colorless.
(2) Primary aromatic aminesTo 0.50 g of Iotalamic Acid, add 15 mL of water and dissolve in 1 mL
of sodium hydroxide TS while ice-cooling. Add 4 mL
of a solution of sodium nitrite (1 in 100) to the solution,
immediately add 12 mL of 1 mol/L hydrochloric acid
TS and shake gently. Then allow the mixture to stand
for exactly 2 minutes, add 8 mL of ammonium sulfamate TS and shake occasionally for 5 minutes. Add 3
drops of a solution of -naphthol in ethanol (1 in 10),
allow to stand for 1 minute, add 3.5 mL of ammoniaammonium chloride buffer solution, pH 10.7, mix and
immediately add water to make 50 mL. Determine
within 20 minutes the absorbance of this solution at
485 nm as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared in the same
manner, as the blank: the absorbance is not more than
0.25.
(3) Soluble halidesDissolve 0.5 g of Iotalamic
Acid in 20 mL of diluted ammonia TS (1 in 40), add 6
mL of dilute nitric acid, shake, allow to stand for 5 minutes and filter. Transfer the filtrate to a Nessler tube,
wash the residue with 20 mL of water, combine the fil-
KP 9 529
trate and the washings and add water to make 50 mL.
Proceed as directed for the Chloride Limit Test using
this solution as the test solution. Prepare the control solution as follows: to 0.10 mL of 0.01 mol/L hydrochloric acid VS and add 20 mL of diluted ammonia TS (1 in
40), 6 mL of dilute nitric acid and water to make 50 mL.
(4) IodineDissolve 0.20 g of Iotalamic Acid in
2.0 mL of sodium hydroxide TS, add 2.5 mL of 0.5
mo1/L sulfuric acid TS and allow to stand for 10 minutes with occasional shaking. Add 5 mL of chloroform, shake well and allow to stand: the chloroform
layer remains colorless.
(5) Heavy metalsProceed with 1.0 g of Iotalamic
Acid according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Iotalamic Acid according to Method 3 and perform the
hours).
Assay Weigh accurately about 0.4 g of Iotalamic Acid, previously dried, place in a flask, dissolve in 40 mL
of sodium hydroxide TS, add 1 g of zinc powder and
heat for 30 minutes under a reflux condenser. Cool, filter, wash the flask and the filter paper with 50 mL of
water and combine the washings and the filtrate. Add 5
mL of glacial acetic acid to this solution and titrate with
0.1 mol/L silver nitrate VS, until the color of the precipitate changes from yellow to green (indicator: 1 mL of
tetrabromophenolphthalein ethyl ester TS).

= 20.464 mg of C11H9I3N2O4

tight containers.
Ipratropium Bromide Hydrate

H
O
O
H3CNCH(CH 3)2
H
CH
Br
H2 O
CH2OH
C20H30BrNO3H2O: 430.38
Ipratropium Bromide, when dried, contains not less
than 99.0% and not more than 101.0% of ipratropium
bromide (C20H30BrNO3: 412.36).
Description Ipratropium Bromide is a white, crystalline powder.

Ipratropium Bromide is freely soluble in water, soluble
in dehydrated ethanol, slightly soluble in acetonitrile or
in glacial acetic acid and practically insoluble in ether.
pHThe pH of a solution of Ipratropium Bromide
Melting pointAbout 223 C (with decomposition,
after drying).
Identification (1) To 5 mg of Ipratropium Bromide,
add 0.5 mL of fuming nitric acid and evaporate on a
water-bath to dryness. After cooling, dissolve the residue in 5 mL of acetone and add 2 drops of potassium
hydroxide-ethanol TS: a purple color develops.
Ipratropium Bromide and Ipratropium Bromide RS in
0.01 mol/L hydrochloric acid TS (3 in 2000) as directed
same wavelength. maxima .
(3) Determine the infrared spectra of Ipratropium
Bromide and Ipratropium Bromide RS as directed in
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumber.
(4) The solution of Ipratropium Bromide (1 in 100)
responds to the Qualitative Tests for bromide.
1.0 g of Ipratropium Bromide in 20 mL of water: the
(2) SulfatePerform the test with 1.0 g of Ipratropium Bromide. Prepare the control solution with 0.50
0.024%).
(3) Heavy metalsProceed with 2.0 g of Ipratropium Bromide according to Method 4 and perform the
test. Prepare the control solution with 2.0 mL of standard lead solution (not more than 10 ppm).
Ipratropium Bromide according to Method 4 and perform the test (not more than 1 ppm).
(5) Isopropylatropine bromideDissolve 25 mg of
Ipratropium Bromide in the mobile phase to make exactly 100 mL and use this solution as the test solution.
Perform the test with 25 L of the test solution as directed under the Liquid Chromatography according to
the following conditions. Determine the peak area, Aa,
of ipratropium and the peak area, Ab, having a ratio of
the retention time to ipratropium about 1.3 by the automatic integration method: Ab/(Aa +Ab) is not more
than 0.01 and no peak other than the peak of ipratropium and the peak having a ratio of the retention time
to ipratropium about 1.3 appears within about 14 minutes of the retention time after the solvent peak.

Column: A stainless steel column, about 4 mm in
inside diameter and 10 cm to 15 cm in length, packed
with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase: A mixture of diluted phosphoric acid
(1 in 200), acetonitrile and methanesulfonic acid
(1000 : 120 : 1).
time of ipratropium is about 7 minutes.
System suitability
System performance: Heat a solution of Ipratropium Bromide in 1 mol/L hydrochloric acid TS (1 in
100) at 100 C for 1 hour and cool. To 2.5 mL of this
solution, add the mobile phase to make 100 mL. When
the procedure is run with 25 L of this solution according to the above operating conditions, the resolution,
between the peak of ipratropium and the peak having a
ratio of the retention time to ipratropium about 0.6, is
not less than 3.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of ipratropium obtained
from 25 L of the test solution composes 50% to 80%
of the full scale.
(6) Apo-compoundsDissolve 0.14 g of Ipratropium Bromide in 0.01 mol/L hydrochloric acid TS to
make 100 mL. Perform the test with this solution as directed under the Ultraviolet-visible Spectrophotometry
and determine the absorbances, A1 and A2, at 246 nm
and 263 nm, respectively: A1/A2 is not more than 0.91.
Loss on Drying Between 3.9% and 4.4% (1 g, 105
C, 4 hours).
Assay Weigh accurately about 0.3 g of Ipratropium
Bromide, previously dried, dissolve in 40 mL of glacial
acetic acid, add 40 mL of dioxane and 2.5 mL of bismuth nitrate TS and titrate with 0.1 mol/L per chloric
acid VS (potentiometric titration, Endpoint Detection
Method in Tetrimetry). Perform a blank determination

= 41.24 mg of C20H30BrNO3
Isoconazole Nitrate
Cl
Cl
Cl
HNO3
O
N
Cl
N
and enantiomer
C18H14Cl4N2OHNO3 : 479.14
Isoconazole Nitrate contains not less than 99.0% and

not more than 101.0% of isoconazole nitrate
(C18H14Cl4N2OHNO3), calculated on the dried basis.
Description Isoconazole Nitrate is a white powder.
Isoconazole Nitrate is soluble in methanol, slightly soluble in ethanol, and very slightly soluble in water.
Isoconazole Nitrate and Isoconazole Nitrate RS, previously dried, as directed in the potassium bromide disk
(2) Dissolve 30 mg of Isoconazole Nitrate in 5 mL
of methanol and use as the test solution. Separately,
dissolve 30 mg of Isoconazole Nitrate RS in 5 mL of
methanol and use this solution as the standard solution
(1). Dissolve 30 mg of Isoconazole Nitrate RS and 30
mg of Econazole Nitrate RS in 5 mL of methanol and
use this solution as the standard solution (2). Perform
the test with 5 L each of the test solution and the standard solutions (1) and (2) as directed under Thin Layer
and the standard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate
with a mixture of methanol, dioxane and ammonium
acetate (40 : 40 : 20) to a distance of about 15 cm and
warm air-dry the plate for 15 minutes. Expose this plate
to iodine vapor. The principal spots from the test solution and the standard solution show the same color and
Rf value. This test is valid only if two spots in the
chromatogram obtained with the standard solution (2)
separate clearly.
(3) Weigh the amount of Isoconazole Nitrate,
equivalent to 1 mg of nitric acid, add to a mixture of
0.1 mg of nitrobenzene and 0.2 mL of sulfuric acid and
allow to stand for 5 minutes. Cool on ice water and add
5 mL of water slowly with stirring. When 5 mL of 10
mol/L sodium hydroxide TS and 5 mL of acetone were
added and allowed to stand, the upper layer turn into
dark violet.
Melting Point
KP 9 531
D : between -0.10 and
+0.10 (0.2 g, methanol, 20 mL, 100 mm)
Purity (1) Clarity and color of solutionTo 0.2 g of
Isoconazole Nitrate add methanol to make 20 mL: it is
clear.
(2) Related substancesWeigh accurately 0.10 g
of Isoconazole Nitrate, dissolve in mobile phase to
make exactly 10 mL and use this solution as the test solution. Separately, dissolve 2.5 mg of Isoconazole Nitrate RS and 2.5 mg of Econazole Nitrate RS in mobile
the standard solution (1). To 1.0 mL of the test solution
add mobile phase to make exactly 100 mL, pipet 5.0 ml
of this solution, add mobile phase to make exactly 20
Perform the test with exactly 10 L each of the test and
standard solutions (2) as directed under Liquid Chromatography according to the following conditions, and
determine each peak area by the automatic integration
method: the area of any peak other than the principal
peak in the chromatogram from the test solution is not
greater than the area of the principal peak from the
standard solution (2) (0.25%); the total area of all peaks
other than the principal peak with the test solution is
not greater than twice the area of the principal peak in
the chromatogram from the standard solution (2)
(0.5%). Disregard any peaks due to the solvent. nitrate
ion and any peak with an area less than 0.2 times that
of the principal peak in the chromatogram from the
diameter and 10 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (3 m in
particle diameter).
Mobile phase: Dissolve 6 g of ammonium acetate in a
mixture of water, methanol and acetonitrile (380 : 320 :
300).
System suitability
operating condition, econazole and isoconazole are
eluted in this order with the retention times being about
10 minutes and 14 minutes, respectively and resolution
between the peaks of econazole and isoconazole is nol
less than 5.0.
Sensitivity of the system: Adjust so that the
height of the principal peak in the chromatogram obtained with 10 L of the standard solution (2) is at least
50% of the full scale of the recorder.
hours).
Assay Weigh accurately about 0.35 g of Isoconazole

Nitrate, add 75 ml of a mixture of methyl ethyl ketone
and anhydrous acetic acid (7 : 1) and titrate with 0.1
mol/L perchloric acid VS (potentiometric titration,
Endpoint Detection Method in Titrimetry).

= 47.91 mg of C18H15Cl4N3O4.
Preserve in light-resistant

Isoflurane
F
Cl
H
F
O
F
F
and enantiomer
C3H2ClF5O: 184.49
Isoflurane contains not less than 99.0% and not more

than 101.0% of isoflurane (C3H2ClF5O), calculated on
Description Isoflurane is a clear, colorless fluidal
liquid.
Isoflurane is slightly soluble in water. Isoflurane is
miscible with ethanol, methanol or o-xylene. Isoflurane
is volatile, and has no inflammability.
Isoflurane shows no optical rotation.
Refractive Index nD20 : about 1.30
Boiling PointBetween 47 C and 50 C
Identification (1) The test solution obtained by the
Oxygen Flask Combustion Method with 50 L of Isoflurane, using 40 mL of water as the absorbing liquid,
responds to the Qualitative Tests for chloride and fluoride.
(2) Determine the infrared spectra of Isoflurane and
Isoflurane RS as directed in the liquid film method under Infrared Spectrophotometry, respectively: both
same wave numbers.
Specific Gravity
20
: Between 1.500 and 1.520
d 20
Purity (1) Acidity or alkalinityTo 10 mL of Isoflurane add 5 mL of freshly boiled and cooled water, and
shake for 1 minute: the water layer is neutral.
(2) Soluble chlorideTo 60 g of Isoflurane add 40
mL of water, shake thoroughly, and separate the water
layer. To 20 mL of the water layer add 6 mL of dilute
nitric acid and water to make 50 mL. Perform the test
with this solution as the test solution directed under
Chloride Limit Test. Prepare the control solution with

than 3 ppm).
(3) Soluble fluorideTo 6 g of Isoflurane add 12
mL of diluted 0.01 mol/L sodium hydroxide TS (1 in
20), and shake for 10 minutes. Transfer 4.0 mL of the
0.01 mol/L sodium hydroxide TS (1 in 20) layer into a
Nessler tube, add 30 mL of a mixture of alizarin complexone TS, acetic acidpotassium acetate buffer solution (pH 4.3) and cerium (III) nitrate TS (1 : 1 : 1),
add water to make 50 mL, allow to stand for 60 minutes, and use this solution as the test solution. Separately, to 0.4 mL of the fluorine standard solution and
4.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1
in 20) in a Nessler tube add 30 mL of the mixture of
alizarin complexone TS, acetic acid-potassium acetate
buffer solution (pH 4.3) and cerium (III) nitrate TS (1 :
1 : 1), then proceed in the same manner as for the preparation of the test solution, and use the solution so obtained as the standard solution. Determine the absorbances of the test solution and the standard solution at
600 nm, respectively, as directed under Ultravioletvisible Spectrophotometry, using a solution, obtained
by proceeding in the same manner as above with 4.0
mL of diluted 0.01 mol/L sodium hydroxide TS (1 in
20), as the blank: the absorbance of the test solution is
not more than that of the standard solution (not more
than 2 ppm).
(4) Related substancesUse Isoflurane as the test
solution. To exactly 1 mL of the test solution add oxylene to make exactly 100 mL. Pipet exactly 1 mL of
this solution, add o-xylene to make exactly 100 mL,
the test with exactly 5 L each of the test solution and
the standard solution as directed under Gas Chromatography according to the following conditions, and determine each peak area by the automatic integration
method: the area of the peak other than isoflurane is not
more than the peak area of isoflurane from the standard
solution, and the total area of all peaks other than isoflurane is not more than 3 times the peak area of isoflurane from the standard solution.
Detector, column, column temperature, carrier gas,
and flow rate: proceed as directed in the operating conditions in the Assay.
System suitability
System performance and System repeatability :
proceed as directed in System suitability under the Assay.
Test for required detectability: To exactly 1 mL
of the standard solution add o-xylene to make exactly 2
mL. Confirm that the peak area of isoflurane obtained
that with 5 L of the standard solution.
Time span of measurement: About 5 times as
long as the retention time of isoflurane after injection
of the test solution.
(5) PeroxideTo 10 mL of Isoflurane add 1 mL of

a solution of potassium iodide (1 in 10), freshly prepared, shake vigorously, and allow to stand in a dark
place for 1 hour: the water layer is not yellow.
(6) Residue on evaporationPipet exactly 65 mL
of Isoflurane, evaporate on a water bath, and dry the residue at 105 C for 1 hour: not more than 1 mg.
Fluorine standard solution: Dissolve exactly 2.21 g of
sodium fluoride in water to make exactly 1000 mL. Pipet exactly 10 mL of this solution, and add water to
make exactly 1000 mL. Each mL of this solution contains 0.01 mg of fluorine (F).
Water Not more than 0.1% (2 g, Coulometric titration).
Assay Pipet exactly 5 mL each of Isoflurane and Isoflurane RS (separately determined water content in the
same manner as Isoflurane), add exactly 3 mL of ethyl
acetate as the internal standard, then add o-xylene to
make exactly 50 mL each. To 5 mL each of these solutions add o-xylene to make 50 mL, and use these solutions as the test solution and the standard solution, respectively. Perform the test with 2 L each of the test
solution and standard solution as directed under Gas
and determine the ratios, QT and QS , of the peak
area of isoflurane to that of the internal standard.
Amount (mg) of isoflurane (C3H2ClF5O)

in 5 mL of Isoflurane
= VS
QT
1000 1.506
QS
VS : Amount of Isoflurane RS, calculated on the anhydrous basis (mL)

20
) of isoflurane
1.506: Specific gravity ( d 20
Column: A stainless steel column about 3 mm in inside diameter and about 3.5 m in length, packed with
siliceous earth for gas chromatography (between 125
and 149 m in particle diameter), coated in 10% with
nonylphenoxypoly(ethyleneoxy)-ethanol for gas chromatography and 15% with polyalkylene glycol for gas
chromatography.
about 80 o C .
time of isolfurane is about 7 minutes.
System suitability
with 2 L of the standard solution under the above operating conditions, isoflurane and the internal standard
are eluted in this order with the resolution between
KP 9 533
above operating conditions, the relative standard deviation of the peak area of isoflurane is not more than
1.0%.
and store at not more than 30 C.
L-Isoleucine
H 5C 2
COOH
CH 3 NH 2
C6H13NO2: 131.17
L-Isoleucine, when dried, contains not less than 98.5%
and not more than 101.0% of L-isoleucine (C6H13NO2).
Description L-Isoleucine is a white crystal or crystalline powder, is odorless or has a slightly bitter taste.
L-Isoleucine is freely soluble in formic acid, sparingly
soluble in water and practically insoluble in ethanol or
in ether.
L-Isoleucine dissolves in dilute hydrochloric acid.
Identification Determine the infrared spectra of LIsoleucine and L-Isoleucine RS, previously dried, as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
D : Between +39.5
and +41.5 (after drying, 1 g, 6 mol/L hydrochloric acid TS. 25 mL, 100 mm).
pH Dissolve 1.0 g of L-Isoleucine in 100 mL of water: the pH of this solution is 5.5 - 6.5.
0.5 g of L-Isoleucine in 20 mL of 1mol/L hydrochloric
acid TS: the solution is clear and colorless.
(2) ChloridePerform the test with 0.5 g of LIsoleucine. Prepare the control solution with 0.30 mL
0.021%).
(3) SulfatePerform the test with 0.6 g of LIsoleucine. Prepare the control solution with 0.35 mL
of 0.005 mol/L sulfuric acid VS (not more than
0.028%).
(4) AmmoniumPerform the test with 0.25 g of LIsoleucine. Prepare the control solution with 5.0 mL of
standard ammonium solution (not more than 0.02%).
(5) Heavy metalsDissolve 1.0 g of L-Isoleucine in
40 mL of water and 2 mL of dilute acetic acid by
warming, cool and add water to make 50 mL. Perform
the test. Prepare the control solution as follows: to 2.0
mL of standard lead solution, add 2 mL of dilute acetic

acid and water to make 50 mL (not more than 20 ppm).
L-Isoleucine according to Method 2 and perform the
test. (not more than 2 ppm).
(7) Other amino acidsDissolve 0.10 g of LIsoleucine in 25 mL of water and use this solution as
add water to make exactly 50 mL. Pipet 5.0 mL of this
the test solution and the standard solution as directed
of the test solution and the standard solution on a plate
plate with a mixture of n-butanol, water and glacial
acetic acid (3 : 1 : 1) to a distance of about 10 cm and
air-dry the plate. Spray evenly the plate with a solution
of ninhydrin in acetone (1 in 50) and heat at 80 C for 5
minutes: the spots other than the principal spot from the
standard solution.
hours).
Residue on Ignition
Assay Weigh accurately about 0.25 g of L-Isoleucine,

previously dried and dissolve in 3 mL of formic acid,
add 50 mL of glacial acetic acid and titrate with 0.1
changes from orange-yellow through yellowish green
to green (indicator: 0.5 mL of -naphtholbenzeine TS).
correction.

= 13.117 mg of C6H13NO2
Isoniazid
N
CONHNH 2
Isonicotinic Acid Hydrazide
C6H7N3O: 137.14
Isoniazid, when dried, contains not less than 98.5% and

not more than 101.0% of isoniazid (C6H7N3O).
Description Isoniazid is a colorless crystal or a white,
Isoniazid is freely soluble in water, in glacial acetic acid, sparingly soluble in ethanol, slightly soluble in acet-

ic anhydride and very slightly soluble in ether.
Identification (1) Dissolve about 20 mg each of Isoniazid and Isoniazid RS in water to make 200 mL and
to 5 mL of these solutions, add 1 mL of 0.1 mol/L hydrochloric acid TS and water to make 50 mL. Determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
the same wavelengths..
(2) Determine the infrared spectra of Isoniazid and
Isoniazid RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Melting Point
pH Dissolve 1.0 g of Isoniazid in 10 mL of freshly

boiled and cooled water: the pH of this solution is between 6.5 and 7.5.
1.0 g of Isoniazid in 20 mL of water: the solution is
(2) Heavy metalsProceed with 1.0 g of Isoniazid
(3) ArsenicPrepare the test solution with 0.40 g
of Isoniazid according to Method 3 and perform the test.
In this case, add 10 mL of a solution of magnesium nitrate in ethanol (1 in 50), then add 1.5 mL of strong hydrogen peroxide water and ignite the ethanol to burn
(4) HydrazineDissolve 0.10 g of Isoniazid in 5
mL of water, add 0.1 mL of a solution of salicylaldehyde in ethanol (1 in 20), shake immediately and allow
to stand for 5 minutes: no turbidity is produced.
hours).
Assay Weigh accurately about 0.3 g of Isoniazid,
previously dried, Dissolve in 50 mL of glacial acetic
acid and 10 mL of acetic anhydride and titrate with 0.1
changes from yellow to seen (indicator: 0.5 mL of naphtholbenzeine TS). Perform a blank determination

= 13.714 mg of C6H7N3O
tight containers.
Isoniazide Injection
Isonicotinic acid hydrazid Injection
Isoniazid Injection is an aqueous solution for injection.
Isoniazid Injection contains not less than 95.0% and not
more than 105.0% of the labeled amount of isoniazid
(C6H7N3O: 137.14).
Method of Preparation Prepare as directed under Injections, with Isoniazide.
Description Isoniazide Injection is a clear, colorless
liquid.
Identification To a volume of Isoniazid Injection,
equivalent to 20 mg of Isoniazid according to the labeled amount, and add water to make 200 mL. To 5 mL
of the solution add 1 mL of 0.1 mol/L hydrochloric acid TS and water to make 50 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry: it exhibits a maximum absorption between 264 - 268 nm.
Foregin Insoluble Matter Test
ment

Assay To an exactly measured volume of Isoniazid
Injection, equivalent to about 50 mg of isoniazid
(C6H7N3O), add water to make exactly 100 mL. Pipet 5
mL of the solution, add exactly 5 mL of the internal
standard and the mobile phase to make 50 mL, and use
this solution as athe sample solution. Separately, weigh
accurately about 50 mg of isoniazid for assay, previously drid at 105 C for 2 hours, and dissolve in water
to make exactly 100 mL. Pipet 5 mL of this solution.
Add exactly 5 mL of the internal standard and the mobile phase to make 50 mL, and use this solution as the
the sample solution and standard solution as directed
under Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS ,
of the peak area of isoniazid to that of the internal standard.
Amount (mg) of isoniazid (C6H7N3O) = amount (mg)

of Isoniazide RS
QT
QS
KP 9 535
(wavelength : 265 nm).
diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in
particle diameter).
about .
Mobile phase: Disssolve 6.80 g of potassium dihydrogen phosphate in water to make 1000 mL. Separately, to 5.76 g of phosphoric acid add water to make 1000
mL. Mix these solutions to make a solution having pH
2.5. To 500 mL of this solution add 500 mL of methanol, and add 2.86 g of sodium tridecanesulfonate to dissolve.
time of isoniazid is about 5 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, isoniazid and the internal standard
are eluted in this order with the resolution between
above operating conditions, the relative standard deviation of the ratios of the peak areas of isoniazid to that of
lution 20 minutes after starting the test and filter

through a membrane filter with pore size of not more
than 0.45 m. Discard the first 10 mL of the filtrate,
pipet 5.0 mL of the subsequent, add water to make exactly 50 mL and use this solution as the test solution.
Separately, weigh accurately about 0.10 g of Isoniazid
RS, previously dried at 105 C, for 2 hours, dissolve in
water to make exactly 100 mL, then pipet 5.0 mL of
this solution, add water to make exactly 50 mL and
then pipet 5.0 mL of this solution, add water to make
exactly 50 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of
the test solution and the standard solution, respectively,
at 267 nm as directed under the Ultraviolet-visible
Spectrophotometry.
The dissolution rate of Isoniazid Tablets in 20 minutes
Light-resistant, hermetic

Isoniazid Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.10 g of isoniazid
(C6H7N3O), add 150 mL of water, shake for 30 minutes,
then add water to make exactly 200 mL and filter. Discard the first 10 mL of the filtrate, pipet 5.0 mL of the
subsequent filtrate, add the mobile phase to make exactly 50 mL and use this solution as the test solution.
Separately, weigh accurately about 50 mg of Isoniazid
RS, previously dried at 105 o C for 2 hours, dissolve in
water to make exactly 100 mL. Pipet 5.0 mL of this solution, add the mobile phase to make exactly 50 mL
the test with 10 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine the peak areas, AT and AS , of Isoniazid of the test solution and the standard solution, respectively.

containers.
Isoniazid Tablets
Isonicotinic Acid Hydrazide Tablets
Isoniazid Tablets contain not less than 95.0% and not
more than 105.0% of the labeled amount of isoniazid
(C6H7N3O: 137.14).
Tablets, with Isoniazid.
Identificatlon Take a portion of powdered Isoniazid

Tablets, equivalent to 20 mg of Isoniazid according to
the labeled amount, add 200 mL of water, shake well
and filter. To 5 mL of the filtrate, add 1 mL of 0.1
mol/L hydrochloric acid TS and water to make 50 mL
and determine the absorption spectrum of this solution
as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 264 nm and 268
nm.
Isoniazid Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of water. Take 20 mL or more of the dissolved so-
Dissolution rate (%) with respect to the labeled

amount of isoniazid (C6H7N3O) = W S
AT 90
AS
C
WS : Amount (mg) of Isoniazid RS.

C: Labeled amount (mg) of isoniazid (C6H7N3O) in
1 tablet.

ment.
Amount (mg) of isoniazid (C6H7N3O)

= amount (mg) of Isoniazid RS
AT
AS
Operoting condition

octadecysilanized silica gel for liquid chromatography
about 40 C.
Mobile phase: Dissolve 6.80 g of monobasic potassium phosphate in water to make 1000 mL. Separately,
dissolve 5.76 g of phosphoric acid in water to make
1000 mL. Mix these solutions, to adjust the pH to 2.5.
To 400 mL of this solution, add 600 mL of methanol
and dissolve 2.86 g of sodium tridodecane sulfonate.
time of Isoniazid is about 5 minutes.
System suitability
System performance: Dissolve 5 mg of Isoniazid
and 5 mg of isonicotinic acid in 100 mL of the mobile
phase. When the procedure is run with 10 L of this solution under the above operating conditions, isonicotinic acid and Isoniazid are eluted in this order with the
above operatig conditions, the relative standard deviation of the ratios of the peak area of isoniazid to that of
tight containers.
Isophane Iusulin Injection

Isophane Insulin Injection (Aqueous Suspension) is an
aqueous suspension for injection. Isophane Insulin Injection contains not less than 90.0% and not more than
110.0% of the labeled insulin units and not less than
0.01 mg and not more than 0.04 mg of zinc (Zn: 65.41)
for each labeled 100 units. When sodium chloride is
used in the preparation of Isophane Insulin Injection
(Aqueous Suspension), this should be stated on the label.
Method of Preparation Prepare as directed under Injections, with Insulin and Protamine Sulfate. To each
100 mL of Isophane Insulin Injection (Aqueous Suspension), add either 0.38 to 0.63 g of dibasic sodium
phosphate, 1.4 to 1.8 g of concentrated glycerin, 0.15 to
0.17 g of cresol and 0.06 to 0.07 g of phenol, or 0.38 to
0.63 g of dibasic sodium phosphate, 0.42 to 0.45 g of
sodium chloride, 0.7 to 0.9g of concentrated glycerin
and 0.18 to 0.22 g of cresol.
Description Isophane Insulin Injection (Aqueous
Suspension) is a white aqueous suspension. When allowed to stand, it separates into a white precipitate and
colorless supernatant liquid and the precipitate returns
easily to the suspension state on gentle shaking. When
examined microscopically, the precipitate mostly con-
sists of fine, oblong crystals of 5 to 30 m in major axis

and does not contain amorphous substances or large
aggregates.
Identification Adjust the pH of Isophan Insulin Injection (Aqueous suspension to Between 2.5 and 3.5
with dilute hydrochloric acid; Particles dissolve and the
solution is clear and colorless..
pH
Between 7.0 and 7.4
Purity (1) ProteinPerform the test as directed under the Nitrogen Determination: not exceeding 0.85 mg
of nitrogen is found for each labeled 100 units.
(2) Isophane ratio (i) Buffer solution A: Dissolve
2.0 g of anhydrous dibasic sodium phosphate, 16 g of
glycerin, 1.6 g of m-cresol and 0.65 g of phenol in water to make exactly 200 mL.
(ii) Buffer solution B: Dissolve 2.0 g of anhydrous dibasic sodium phosphate, 4.35 g of sodium chloride, 8.0
g of glycerin and 2.0 g of n-cresol in water to make exactly 200 mL.
(iii) Insulin solution: Weigh accurately 1000 units of
insulin RS, dissolve in 1.5 mL of diluted hydrochloric
acid (1 in 360) and add 5.0 mL of buffer solution A and
water to make 20 mL. Adjust the pH to 7.2 with dilute
hydrochloric acid or sodium hydroxide TS. The solution is clear. Dilute with water to make exactly 25 mL,
The solution is clear and the pH is between 7.1 and 7.4.
When it is stated on the label that sodium chloride is
used in the preparation, use 5.0 mL of buffer solution B
instead of buffer solution A in the above procedure.
(iv) Protamine solution: Weigh accurately 50 mg of
protamine sulfate RS and dissolve in 2 mL of buffer solution A and water to make 8 mL. Adjust the pH to 7.2
with dilute hydrochloric acid or sodium hydroxide TS
and dilute with water to exactly 10 mL. The solution is
clear and the pH is between 7.1 and 7.4. When it is
stated on the label that sodium chloride is used in the
preparation, use 2 mL of buffer solution B instead of
buffer solution A in the above procedure.
(v) Procedure: When Isophane Insulin Injection
(Aqueous Suspension) contains 40 units per ml, centrifuge a portion of the suspension, measure exactly two
10 mL volumes of the supernatant liquid in two tubes A
and B, respectively, add exactly 1 mL of the Insulin solution to tube, A and 1 mL of the protamine solution to
tube B, mix the contents of each tube, allow to stand
for 10 minutes and determine the turbidity of each mixture by using a photometer or a nephelometer: the turbidity of the mixture in tube B is not greater than that in
tube A. When Isophane Insulin Injection (Aqueous
Suspension) contains 80 units per ml, measure exactly
5 mL of the supernatant liquid and proceed in the same
manner.
KP 9 537
Assay (1) InsulinTake Isophane Insulin Injection
(Aqueous Suspension), add diluted hydrochloric acid (1
in 100) to adjust pH to about 2.5 and proceed with the
clear solution as directed in the Assay under Insulin Injection.
(2) ZincPipet a volume of Isophane Insulin Injection (Aqueous Suspension), equivalent to about 400
units according to the labeled units, add 1 mL of 0.1
mol/L hydrochloric acid TS and water to make exactly
100 mL, dilute, if necessary, with water to contain 0.6
to 1.0 g of zinc pet mL and use this solution as the test
solution. Separately, pipet a volume of standard zinc
solution for the Atomic Absorption Spectrophotometry,
dilute with water to contain 0.4 to 1.2 g of zinc per
mL and use this solution as the standard solution. Perform the test with the test solution and the standard solution according to the Atomic Absorption Spectrophotometry under the following conditions and determine
the amount of zinc in the test solution using the analytical curve obtained from the absorbance of the standard
solution.

Supporting gas-Air.
Purity (1) Clarity and color of solutionTo 2.0 mL

of Isopropanol, add 8 mL of water and shake: the solution is clear.
(2) AcidTo 15.0 mL of Isopropanol, add 50 mL
of freshly boiled and cooled water and 2 drops of phenolphthalein TS and add 0.40 mL of 0.01 mol/L sodium hydroxide VS: a red color develops.
(3) Residue on evaporationEvaporate 20.0 mL
of Isopropanol on a water-bath to dryness and dry at
105 C for 1 hour: the weight of the residue is not more
than 1.0 mg.
Water Not more than 0.75% (2 mL, volumetric titration, direct titration).
Between 81 C and 83 C, not less
Distilling Range
than 94 vol%.
Packaging and Storage Preserve in remoting from

fire, tight containers.
Isopropylantipyrine
CH3
H3C
Packaging and Storage Preserve in hermetic containers in a cold place and avoid freezing.
N
N
H3C
CH
O
CH3
Propyphenazone
Isopropanol
Isopropylantipyrine, when dried, contains not less than

98.0% and not more than 101.0% of isopropylantipyrine (C14H18N2O).
OH
CH3CHCH3
Isopropyl Alcohol
C3H8O: 60.10
Description Isopropanol is a clear, colorless liquid

and has a characteristic odor.
Isopropanol is miscible with water, with methanol, with
ethanol,or with ether.
Isopropanol is flammable and volatile.
Identification (1) To 1 mL of Isopropanol, add 2 mL
of iodine TS and 2 mL of sodium hydroxide TS and
shake: pale yellow precipitate is formed.
(2) To 5 mL of Isopropanol, add 20 mL of potassium dichromate TS and 5 mL of sulfuric acid with
caution and warm gently on a water-bath: the produced
gas has the odor of acetone and the gas turns the filter
paper, previously wetted with a solution of salicylaldehyde in ethanol (1 in 10) and with a solution of sodium
hydroxide (3 in 10), to red brown.
Specific Gravity
C14H18N2O: 230.31
20
: Between 0.785 and 0.788
d 20
Description Isopropylantipyrine is a white crystal or

taste.
Isopropylantipyrine is very soluble in glacial acetic acid, freely soluble in ethanol or in acetone, soluble in
ether and slightly soluble in water.
Identification (1) To 2 mL of a solution of Isopropylantipyrine (1 in 500), add 1 drop of ferric chloride TS:
a pale red color develops. Further add 3 drops of sulfuric acid to this solution: the color changes to pale yellow.
(2) Add 5 mL of a solution of Isopropylantipyrine
(1 in 500) to a mixture of 5 mL of potassium ferricyanide TS and 1 to 2 drops of ferric chloride TS: A dark
green color gradually develops.
(3) To 2 mL of a solution of Isopropylantipyrine (1
in 500), add 2 to 3 drops of tannic acid TS: a white precipitate is produced.
Melting Point
Purity (1) ChlorideDissolve 1.0 g of Isopropylan-

tipyrine in 30 mL of dilute ethanol and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the
test. Prepare the control solution as follows: to 0.40 mL
of 0.01 mol/L hydrochloric acid VS, add 6 mL of dilute
nitric acid, 30 mL of dilute ethanol and water to make
(2) SulfateDissolve 1.0 g of Isopropylantipyrine
in 30 mL of dilute ethanol and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the
test. Prepare the control solution as follows: to 0.40 mL
of 0.005 mol/L sulfuric acid VS, add 1 mL of dilute
hydrochloric acid and 30 mL of dilute ethanol and dilute with water to make 50 mL (not more than 0.019%).
(3) Heavy metalsDissolve 1.0 g of Isopropylantipyrine in 25 mL of acetone, add 2 mL of dilute acetic
acid and water to make 50 mL and perform the test.
standard lead solution, add 2 mL of dilute acetic acid,
25 mL of acetone and dilute with water to make 50 mL
Isopropylantipyrine according to Method 3 and perform
(5) AntipyrineDissolve 1.0 g of Isopropylantipyrine in 10 mL of dilute ethanol and add 1 mL of sodium
nitrite TS and 1 mL of dilute sulfuric acid: no green
color develops.
less than 97.0% and not more than 101.5% of isoproterenol hydrochloride (C11H17NO3HCl).


1.0 g of Isoproterenol Hydrochloride in 20 mL of 0.1
mol/L hydrochloric acid TS: the solution is clear and
colorless.
(2) SulfatePerform the test with 0.10 g of Isoproterenol Hydrochloride. Prepare the control solution
with 0.40 mL of 0.005mol/L sulfuric acid VS (not more
than 0.2%).
(3) IsoproterenoneDissolve 50 mg of Isoproterenol Hydrochloride in 0.01 mol/L hydrochloric acid TS
to make exactly 25 mL and determine the absorbance
of the solution at 310 nm as directed under the Ultraviolet-visible Spectrophotometry: not more than 0.2.

Assay Weigh accurately about 0.4 g of Isopropylantipyrine, previously dried, dissolve in 60 mL of a mixture
of glacial acetic acid and acetic anhydride (2 : 1) and titrate with 0.1 mol/L perchloric acid VS (potentiometric
titration, Endpoint Detection Method in Titrimetry),
correction.

= 23.031 mg of C14H18N2O
Description Isoproterenol Hydrochloride is a white,

Isoproterenol Hydrochloride is freely soluble in water,
sparingly soluble in ethanol and practically insoluble in
glacial acetic acid, in acetic anhydride, in ether or in
chloroform.
Isoproterenol Hydrochloride is gradually colored by air
and by light.
Identification (1) Determine the absorption spectra
of solutions of Isoproterenol Hydrochloride and Isoproterenol Hydrochloride RS in 0.1 mol/L hydrochloric acid TS(1 in 20000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit the
(2) Determine the infrared spectra of Isoproterenol
Hydrochloride and Isoproterenol Hydrochloride RS,
previously dried, as directed in the potassium disk method under the Infrared Spectrophotometry: both spectra exhibit the similar intensities of absorption at the
same wavenumbers.
Melting Point Between 165 o C and 170 o C .

Isoproterenol Hydrochloride
OH
H
N
CH3
HCl
H
CH3
HO
OH
Isoprenaline hydrochloride
and enantiomer
C11H17NO3HCl: 247.72
Isoproterenol Hydrochloride, when dried, contains not
Assay Weigh accurately about 0.125 g of Isoproterenol Hydrochloride, dissolve in a solution of sodium bisulfite (3 in 1000), dilute with the solution of sodium
bisulfite to make 25 mL and mix. Transfer 5.0 mL of
this solution, dilute with 0.17 mol/L acetic acid to make
exactly 100 mL and mix. Use this solution as the test
solution. Separately, weigh accurately a portion of Isoproterenol Hydrochloride RS to make a solution containing about 2.5 mg per mL and dissolve in mobile
phase. Pipet 5.0 mL of this solution and dilute with
0.17 mol/L acetic acid to make exactly 50 mL. Use this
10 L each of the test solution and the standard solu-
KP 9 539
tion as directed under the Liquid Chromatography. Determine, AT and AS , the peak areas of isoproterenol
Amount (mg) of isoproterenol hydrochloride
(C11H17NO3.HCl) = 0.5 C
AT
AS
C: Concentration (g/mL) of Isoproterenol Hydrochloride RS in the standard solution.

Mobile phase: 0.17 mol/L of acetic acid.
System suitability
System repeatabily: When the test is repeated 6
standard deviation of the peak area of isoproterenol is
not more than 3.0%.

Isosorbide
H
HO
O
H
H
OH
C6H10O4: 146.14
Isosorbide, contains not less than 98.5% and not more
than 101.0% of isosorbide (C6H10O4), calculated on the
anhydrous basis.
Description Isosorbide is a white crystal or mass, is
odorless or has a faint, characteristic odor and has a bitter taste.
Isosorbide is very soluble in water or in methanol, freely soluble in ethanol and slightly soluble in ether.
Isosorbide is hygroscopic.
Identification (1) To 0.1 g of Isosorbide, add 6 mL
of diluted sulfuric acid (1 in 2) and dissolve by heating
in a water-bath. After cooling, shake well with 1 mL of
a solution of potassium permanganate (1 in 30) and
heat in a water-bath until the color of potassium permanganate disappears. To this solution, add 10 mL of
2,4-dinitrophenylhydrazine TS and heat in a water-
bath: an orange preciptate is formed.

(2) To 2 g of Isosorbide, add 30 mL of pyridine and
4 mL of benzoyl chloride, boil under a reflux condenser
for 50 minutes, cool and pour gradually the solution into 100 mL of cold water. Filter the formed precipitate
by suction through a glass filter (G3), wash with water,
recrystallize twice from ethanol and dry in a desiccator
(in vacuum, silica gel) for 4 hours: it melts between
102 o C and 103 o C .
(3) Determine the infrared spectrum of Isosorbide
and Isosorbide TS as directed in the potassium bromide
disk method under the Infrared Spectrophotometry:
D : Between +45.0
and +46.0 (5 g, calculated on the anhydrous basis, water, 50 mL, 100 mm).
Purity (1) Clarity and color of solutionTake 25 g
of Isosorbide in a Nessier tube and dissolve in 50 mL
of water: the solution is clear and has no more color
Control solutionTo a mixture of 1.0 mL of cobaltous chloride stock CS, 3.0 mL of ferric chloride
stock CS and 2.0 mL of cupric sulfate stock CS, add
water to make 10.0 mL. To 3.0 mL of this solution, add
(2) SulfatePerform the test with 2.0 g of Isosorbide. Prepare the control solution with 1.0 mL of 0.005
mol/L sulfuric acid VS (not more than 0.024%).
(3) Heavy metalsProceed with 5.0 g of Isosorbide according to Method 1 and perform the test. Prepare the control solution with 2.5 mL of standard lead
Isosorbide according to Method 1 and perform the test
(5) Related substancesDissolve 0.10 g of Isosorbide in 10 mL of methanol and use this solution as the
test solution. Pipet 2.0 mL of the test solution, add methanol to make exactly 100 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the
Thin-layer Chromatography. Spot 10 L each of the
test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate
with a mixture of ethanol and cyclohexane (1 : 1) to a
evenly a mixture of ethanol and sulfuric acid (9 : 1) on
the plate and heat at 105 C for 30 minutes: the spots
other than the principal spot from the test solution are
direct titration).

Assay Weigh accurately about 10 g of Isosorbide and
dissolve in water to make exactly 100 mL. Determine
the optical rotation, D , of this solution at 20 1 C
in a 100 mm cell.
Amount (g) of isosorbide (C6H10O4) = D 2.1978

Isosorbide Dinitrate
ONO 2
H
H
O
O
H
H
ONO 2
C6H8N2O8: 236.14
Isosorbide Dinitrate, contains not less than 95.0% and
not more than 101.0% of isosorbide dinitrate
(C6H8N2O8), calculated on the anhydrous basis.
Description Isosorbide Dinitrate is a white crystal or
crystalline powder, is odorless or has a faint odor like
that of nitric acid.
Isosorbide Dinitrate is very soluble in dimethylformamide or in acetone, freely soluble in chloroform or in
toluene, soluble in methanol, in ethanol or in ether and
Isosorbide Dinitrate explodes if heated quickly or subjected to percussion.
Identification (1) Dissolve 10 mg of Isosorbide Dinitrate in 1 mL of water and dissolve by adding 2 mL of
sulfuric acid cautiously. After cooling, superimpose 3
mL of ferrous sulfate TS and allow to stand for 5
minute to 10 minutes: a brown ring is produced at the
zone of contact.
(2) Dissolve 0.1 g of Isosorbide Dinitrate in 6 mL
of diluted sulfuric acid (1 in 2) by heating in a waterbath. After cooling, add 1 mL of a solution of potassium permanganate (1 in 30), stir well and heat in a water-bath until the color of potassium permanganate disappears. Add 10 mL of 2,4-dinitrophenylhydrazine TS
and heat in a water-bath: an orange precipitate is produced.
D : Between + 134
and + 139 (1 g, calculated on the anhydrous basis,
ethanol, 100 mL, 100 mm).
1.0 g of Isosorbide Dinitrate in 10 mL of acetone: the
(2) SulfateDissolve 1.5 g of Isosorbide Dinitrate

in 15 mL of dimethylformamide, add 60 mL of water,
cool and filter. Wash the filter paper with three 20 mL
volumes of water, combine the washings with the filtrate and add water to make 150 mL. To 40 mL of this
solution, add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test. Prepare the control
solution with 0.40 mL of 0.005 mol/L sulfuric acid VS
(3) NitrateDissolve 50 mg of Isosorbide Dinitrate
in 30 mL of toluene and extract with three 20 mL volumes of water. Combine the aqueous layers and wash
with two 20 mL volumes of toluene. To the aqueous
layer, add water to make exactly 100 mL and use this
solution as the test solution. Pipet 5.0 mL of standard
nitric acid solution and 25.0 mL of the test solution in
each Nessler tube and add water to make exactly 50 mL,
respectively. To each of them, add 60 mg of GrissRomijin's nitric acid reagent, stir well, allow to stand
for 30 minutes and observe from the side of the Nessler
tube: the test solution has no more color than the standard solution.
(4) Heavy metalsDissolve 1.0 g of Isosorbide Dinitrate in 30 mL of acetone and add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 30 mL of acetone, 2 mL of dilute acetic acid and water to make 50 mL (not more
than 20 ppm).
Assay Weigh accurately about 0.1 g of Isosorbide
Dinitrate in a Kjedahl flask as described under the Nitrogen Deterimination, dissolve in 10 mL of methanol,
add 3 g of Devardas alloy and 50 mL of water and
connect the flask with the distillation apparatus as described under the Nitrogen Determination. Measure exactly 25 mL of 0.05 mol/L sulfuric acid VS in an absorption flask, add 5 drops of bromocresol greenmethyl red TS and immerse the lower end of the condenser tube in it. Add 15 mL of a solution sodium hydroxide (1 in 2) through the funnel, cautiously rinse the
funnel with 20 mL of water, immediately close the
clamp attached to the rubber tubing, then begin the distillation until the distillate measures 100 mL. Remove
the absorption flask, rinse the end of the condenser tube
with a small quantity of water and titrate the distillate
and the rinsings with 0.1 mol/L sodium hydroxide VS
until the color of the solution changes from red through
pale red-purple to pale bluegreen. Perform a blank determination and make any necessary correction.

= 11.807 mg of C6H8N2O8
KP 9 541
Isosorbide Dinitrate Tablets
C: the amount (%) of Isosorbide Dinitrate in Isosorbide Dinitrate RS
Isosorbide Dinitrate Tablets contain not less than 93.0%

isosorbide dinitrate (C6H8N2O8: 236.14).
Internal standard solutionDissolve 3 g of Nitroglycerin RS (10% diluted with lactose) in 100 mL of

mobile Phase.

Tablets, with Isosorbide Dinitrate.
inside diameter and about 15 cm to 30 cm in length,
packed with octadeylsilanizd silica gel for liquid chromatography (5 m to 10 m in particle diameter).
Mobile phase: To the mixture of methanol and
0.005 mol/L triethylamine solution (50 : 50), add acetic
acid to adjust pH to 5.0.
System suitability
with 10 L of the standard solution under the above
operating conditions, Isosorbide Dinitrate and internal
standard are eluted in this order with a resolution between their peaks being not more than 2.0.
above operating conditions, the relative standard deviation of the ratios of peak area of Isosorbide Dinitrate to
Identification Weigh a portion of powdered Isosorbide Dinitrate Tablets equivalent to 0.1 g of lsosorbide
Dinitrate, according to the labeled amount, add 50 mL
of ether, shake well and filter. Measure 5 mL of the filtrate, evaporate to dryness cautiously, add 1 mL of water to the residue and dissolve by adding 2 mL of sulfuric acid cautiously. After cooling, superimpose 3 mL
of ferrous sulfate TS and allow to stand for 5 to 10 minutes: a brown ring is produced at the zone of contact.
Purity NitrateWeigh accurately a quantity of powdered Isosorbide Dinitrate Tablets, equivalent to 50 mg
of Isosorbide Dinitrate according to the labeled amount,
transfer to a separator, add 30 mL of toluene, shake thoroughly, extract with three 20 mL volumes of water and
proceed as directed in Purity (3) under Isosorbide Dinitrate.
For sublingual tablets, the time limit of the test is 2 minutes and omit the use of the auxiliary disk.

ment.

Isosorbide Dinitrate. Weigh accurately a portion of the
powder, equivalent to about 5 mg of isosorbide dinitrate (C6H8N2O8), dissolve in mobile phase add 5.0 mL
of interal standard solution and mobile phase to make
exactly 20 mL, filtrate and use this filter as the test solution. Separately, 0.2 g of Isosorbide Nitrate RS (25%,
diluted with lactose), dissolve in mobile phase and to
5.0 mL of internal standard solution and mobile phase
standard solution. Perform the test with 10L each of
the test solution and the standard solution as directed
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and
QS ,of the peak area of Isosorbide Dinitrate to that of
the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of isosorbide dinitrate (C6H8N2O8)

= amount (mg) of Isosorbide Dinitrate RS
C
Q
1
T
100 QS 10
Isotretinoin
H3C
CH3
CH3
CH3
CH3
HO
C20H28O2 : 300.44
Isotretinoin contains not less than 98.0% and not more
than 102.0% of isotretinoin (C20H28O2),calculated on
the dried basis.
Description Isotretinoin is a yellow crystal.
Isotretinoin is soluble in chloroform, slightly soluble in
ethanol, in isopropanol or in polyethylene glycol 400,
Identification (1) Determine the absorption spectra
of solutions of a solution of 0.01 mol/L hydrochloric
acid TS in isopropanol (1 in 1000) of Isotretinoin and
Isotretinoin RS (1 in 25000) as directed under the Ultraviolet-Visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave-

lengths.
(2) Determine the infrared spectra of Isotretinoin
and Isotretinoin RS as directed under the paste method
of Infrared Spectrophotometry: both spectra exhibit
Purity (1) Heavy metalsProceed with 1.0 g of Isotretinoin according to Method 2 and perform the test.
(2) TretinoinWeigh accurately about 0.25 g of
Isotretinoin dissolve, in a small amount of dichloromethane TS, and dilute with isooctane accurately to 100
mL and use this solution as the test solution. Separately, weigh accurately about 25 mg of tretinoin RS,
dissolve in a small amount of dichloromethane TS, and
dilute with isooctane acculately to 100 mL and use this
solution as the standard stock solution, add isooctane to
1.0 mL of this solution to make 100 mL and use this
each 20 L of test solution and standard solution as directed under the Liquid Chromatography according to
the following operating conditions. Determine each
peak area of tretinoin from the test solution , AT , and
standard solution , AS , by the automatic integration method. The amount of Tretinoin is not more than 1.0 %
Amount of Tretinoin (%) = 10 C AT

W
AS
times with 50 L of the standard solution according to

the above operating conditions, the relative standard
deviation of the peak of Tretinoin is not more than
2.0%.
Loss on Drying Not more than 0.5% (1 g, room temperature, vaccum, 16 hours)
Assay Weigh accurately about 0.24 g of Isotretinoin,
dissolve in 50 mL of dimethylformamide and titrate
with 0.1 mol/L sodium methoxide VS. [indicator: 3
drops of a solution of thymol blue in dimethyl formamide (1 in 100)] until the color of solution changes
to green. Perform the blank determination and make
Each ml of 0.1 mol/L sodium methoxide VS

= 30.04 mg of C20H28O2.
tight containers filled with an atmosphere of an inert
gas.
Isradipine
CH3
O
H3C
O
CH3
C : Concentration of Tretinoin (g/mL) in the standard solution.

W : Mass of Tretinoin (mg) used in the test.
(wavelength : 352 nm)
porous silica gel for liquid chromatography (5 m in
particle diameter).
Mobile phase: A mixture of isooctane, isopropanol and glacial acetic acid (99.65 : 0.25 : 0.1)
Flow rate: 1 mL/min
System suitability
System performance: Dissolve 25 mg of Isotretinoin RS in a small amount of dichloromethane, dilute
with isooctane to make 100 mL and use this solution as
the system suitability standard solution. Add the system
suitability standard solution to 1 mL of standard stock
solution to make 100 mL and use this solution as the
system suitability solution. When the procedure is run
conditions, the relative retention times of Isotretinoin
and Tretinoin are 0.84 and 1.0, respectively and the
resolution between the peaks of Isotretinoin and Tretinoin is not less than 2.0.
NH
CH3
N
O
OCH3
C19H21N3O5 : 371.39
Isradipine contains not less than 98.0% and not more
than 102.0% of isradipine (C19H21N5O5), calculated on
the dried basis.
Description Isradipine is a yellow, crystalline powder.
Isradipine is freely soluble in acetone, soluble in acetonitrile or in methanol, and practically insoluble in nhexane or in water.
Identification Determine the infrared spectra of Isradipine and Isradipine RS as directed in the potassium
disk method under Infrared Spectrophotometry: both
same wavenumbers.
KP 9 543
Isradipine according to Method 2 and perform the test.
(2) Related substancesWeigh exactly 50 mg of
Isradipine, dissolve in 5.0 mL of methanol, add the
mobile phase to make exactly 25 mL, and use this solution as the test solution. Weigh exactly 6 mg of Isradipine RS, dissolve in 5 mL of methanol, add the mobile
phase to make exactly 100 mL, add the mobile phase to
5.0 mL of this solution to make exactly 50 mL, and use
with each 25 L of the test solution and the standard
according to the following operating conditions. Determine the peak area other than Isradipine peak from
the test solution: the total area of each peak other than
Isradipine peak obtained from the test solution is not
greater than 4 times the peak area of Isradipine obtained from the standard solution (1.2%), the area of
the largest peak other than Isradipine peak obtained
from the test solution is not greater than 1.6 times the
peak area of Isradipine obtained from the standard solution (0.5%), the area of each peak other than the peak
area of Isradipine obtained from the test solution is not
greater than the peak area of Isradipine obtained from
the standard solution (0.3%).
Detector: An ultraviolet-visible spectrophotometry
Mobile phase: A mixture of water, ethanol and tetrahydrofuran (50 : 40 : 10).
inside diameter and 10 cm in length, packed with porous silica gel for liquid chromatography (3 m to 10
System suitability
System performance: Weigh 0.2 g of Isradipine
RS and 10 mg of Isradipine related substance I RS, dissolve in 5 mL of methanol, add the mobile phase to
make 100 mL. Add the mobile phase to 5.0 mL of this
solution to make 50 mL, and use this solution as the solution of the system suitability. When the procedure is
run test with 25 L of this solution as directed under
operating conditions, the resolution between the peak
of isradipine and the peak of isradipine related substance I is not less than 1.5%.
times with 25 L of the standard solution of the system
suitability under the above operating conditions, the
relative standard deviation of the peak area of isradipine is not more than 1.5%.
Time span of measurement: Not less than 3 times
as long as the retention time of Isradipine peak.
Loss on Drying Not more than 0.2% (105 C, 4 hours,
constant mass).

Assay Use the light-resistant containers in this procedure. Weigh accurately about 20 mg of Isradipine, dissolve in 20 mL of methanol, add the mobile phase to
solution. Separately, weigh accurately a constant mass
of Isradipine RS and Isradipine related substances [isopropylmethyl
4-(4-benzofurzanyl)-2,6-dimethyl-3,5pyridinedicarboxylate] RS, dissolve in methanol, add
the mobile phase to make the solutions containing 0.2
mg/mL and 10 g /mL respectively, and use these solutions as the standard solution. Perform the test with 25
the following operating conditions: determine the peak
area, AT and AS , of Isradipine .
Amount (mg) of isradipine C19H21N3O5)

= 100 C AT
AS
C: Concentration (mg/mL) of Isradipine in the standard solution.

Detector: An ultraviolet-visible absorption photometer (wavelength : 326 nm)
Mobile phase: A misture of water , methanol and
tetrahydrofuran (50:40:10)
inside diameter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (between 3 and 10 m in particle diameter).
System suitability
with 25 L of the system suitability under the above
operating conditions, the resolution between isradipine
peak and Isradipine related substance peak are not more
than 1.5.
above operating conditions, the relative standard deviation of the peak area of Isradipine is not more than
1.5%.
tight containers.

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KP 9 21

Loss on Drying Not more than 1.0% (0.5 g, 105 C, 3

obtained from the standard solution (3) composes 50% of

Acetaminophen, when dried, contains not less than

Between 169 C and 172 C.

System performance: When the procedure is run

= amount (mg) of Acetaminophen RS AT 5

Identification (1) To 0.1 g of Acetazolamide, add 5 mL

Purity (1) Clarity and color of solutionDissolve 1.0

Amount (mg) of acetaminophen (C8H9NO2)

Packaging and Storage

sparingly soluble in acetone, slightly soluble in methanol

1000 mL of 0.05 mol/L sodium dihydrogen phosphate

Acetylcholine Chloride for

line Chloride for Injection according to Method 1 and

Insoluble Particulate Matter Test for Injections

Uniformity of Dosage Units It meets the requirement.

Amount (mg) of Acetylcysteine (C5H9NO3S)

Internal standard solutionDissolve of 1 g of dlphenylalanine in freshly prepared sodium metabisulfite

Loss on Drying Not more than 0.1% (1 g, in vacuum

Residue on Ignition Not more than 0.5% (2 g, 600 C).

Assay Weigh accurately about 1.0 g of Acetylcysteine,

Acrinol Hydrate, contains not less than 98.5% and not

C: Concentration of the standard solution (g/mL),

Residue on Ignition Not more than 0.1% (1.0 g).

C: Concentration of Acyclovir RS in the standard solution (g/mL)

Specific Optical Rotation [ ]20

of water. Stir for 30 seconds, pass through a coarse filter,

Between 233 and 238 C

Specific Optical Rotation [ ]20

Residue on Ignition Not more than 0.2% (0.5 g).

WS : Amount (mg) of Ajmaline RS,

well and allow to stand for 20 minutes at 40 1 C in a

Packaging and Storage Preserve in well-closed containers.

Albumin Tannate is a compound of tannic acid and a

Dihydroxyaluminum Allantoinate C4H7AlN4O5: 218.10

Description Alfuzosin Hydrochloride is a white crystalline powder.

Amount (mg) of alfacalcidol (C27H44O2)

= amount (mg) of Alfacalcidol RS

(1 in 50) is between 5.0 and 6.5.

Between 159 C and 163 C.

Purity (1) Clarity and color of solution Dissolve

Residue on Ignition Not more than 0.1% (1 g).

make exactly 10 mL and use this solution as test solution

Identification (1) Boil 20 mg with a mixture of 1 mL

Loss on Drying Not more than 0.1% (2 g, 105 C,

Specific Optical Rotation [ ]20

Each mL of 0.1 mol/L sodium hydroxide VS

Purity (1) Acidity or alkalinityTo a 10 mL solution

Packaging and Storage Preserve in well-closed containers

Residue on Ignition Not more than 0.1% (1 g).

Allopurinol, when dried, contains not less than 98.0%

absorbances, AT and AS , of the test solution and the

Internal standard solutionA solution of 50 mg of

15 L of the standard solution under the above operating

tal or crystalline powder.

Alprostadil, when dried, contains not less than 97.0%

Specific Optical Rotation [ ]20

Between 114 C and 118 C.

Purity Related substancesDissolve 4 mg of Alprostadil in 2 mL of a mixture of acetonitrile and water (9 : 1)

Internal standard solutionA solution of dimethyl

Aluminum Hydroxide Gel