Accessed from 128.83.63.

20 by nEwp0rt1 on Thu Nov 24 02:21:34 EST 2011

3154 Famotidine / Official Monographs

USP 35

Table 1
Approximate Relative
Retention Time
0.4
0.7
0.8
1.2

Relative Response
Factor (F)
1.0
1.0
1.0
1.3

Limit
(%)
1.0
0.5
0.5
0.5

Name
Impurity A 1
Impurity B 2
Impurity C 3
Impurity D 4

13-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylsulfinyl]-N-sulfamoyl-propanamidine
23-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-propanoic

acid

33-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-N-sulfamoyl-propanamide
43-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-propanamide

Uniformity of dosage units 905: meet the requirements.

Assay
Buffer solutionDissolve 13.6 g of sodium acetate trihydrate
in 750 mL of water. Add 1 mL of triethylamine, adjust with
glacial acetic acid to a pH of 6.0, and dilute with water to 1 L.
Mobile phasePrepare a mixture of Buffer solution and acetonitrile (93:7), mix, and degas. Make adjustments if necessar y
(see System Suitability under Chromatography 621).
DiluentDissolve 6.8 g of monobasic potassium phosphate
in 750 mL of water, adjust with 1 M potassium hydroxide to a
pH of 6.0, and dilute with water to 1 L.
System suitability stock solutionTransfer 10 mg of famotidine to a 50-mL volumetric flask, add 1 mL of 0.1 N hydrochloric acid, heat at 80 for 30 minutes, and cool to room
temperature. Add 2 mL of 0.1 N sodium hydroxide, heat at 80
for 30 minutes, cool to room temperature, and neutralize by
adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to
volume. Transfer 10 mL of this solution to a separate 50-mL
volumetric flask containing 5 mg of famotidine dissolved in 8
mL of methanol. Dilute with Diluent to volume. T ransfer 25 mL
of this solution to a 50-mL volumetric flask, and dilute with
Diluent to volume. [ NOTEThis solution is stable for up to 1
month.]
System suitability solutionTransfer approximately 1 to 1.5
mL of the System suitability stock solution to a suitable container,
add 1 drop of hydrogen peroxide solution, and mix well.
[NOTEPrepare fresh daily.]
Standard preparationTransfer about 10 mg of USP Famotidine RS, accurately weighed, into a 100-mL volumetric flask,
add 20 mL of methanol, and sonicate for 5 minutes. Dilute with
Diluent to volume, and mix.
Assay preparationTransfer not fewer than 10 T ablets to a 1L volumetric flask. Add 200 mL of Diluent, and swirl to erode
the Tablets. Add 200 mL of methanol, and stir by mechanical
means at 300 rpm for 1 hour. Dilute with Diluent to volume,
mix, and filter. Quantitatively dilute a portion of the clear filtrate with Diluent to obtain a solution containing about 0.1 mg
of famotidine per mL.
Chromatographic system (see Chromatography 621)The
liquid chromatograph is equipped with a 275-nm detector and
a 4.6-mm 15-cm column that contains packing L1. The column temperature is maintained at 40 . The flow rate is about
1.4 mL per minute. Chromatograph the System suitability solution, and identify the famotidine peak and the peaks due to
impurities listed in Table 1. Record the peak responses as directed for Procedure: the resolution, R, between the impurity C
and famotidine peaks is not less than 1.3; the resolution, R,
between the famotidine and impurity D peaks is not less than
1.3; and the capacity factor, k, for the famotidine peak is not
less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative
standard deviation for replicate injections is less than 2.0%.
ProcedureSeparately inject equal volumes (about 50 L) of
the Standard preparation and the Assay preparation into the
chromatograph, record the chromatograms, and measure the

responses for the major peaks. Calculate the quantity, in mg, of

famotidine (C 8H15N7O2S3) in each T ablet taken by the formula:
C(D/N)(rU / rS)
in which C is the concentration, in mg per mL, of USP Famotidine RS in the Standard preparation; D is the dilution factor
used to prepare the Assay preparation; N is the number of T ablets taken to prepare the Assay preparation; and rU and rS are the
peak areas obtained from the Assay preparation and the Standard preparation, respectively.

Felodipine
.

C18H19Cl2NO4 384.26
3,5-Pyridinedicarboxylic acid 4-(2,3-dichlorophenyl)-1,4dihydro-2,6-dimethyl-, ethyl methyl ester, ( )-.
()-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate [72509-76-3;
86189-69-7].

Felodipine contains not less than 98.0 per cent

and not more than 101.0 per cent of
C18H19Cl2NO4, calculated on the dried basis.
Packaging and storagePreserve in tight, light-resistant
containers, and store at controlled room temperature.
USP Reference standards 11
USP Felodipine RS
Color of solutionPrepare a solution in methanol having a
concentration of 20 mg per mL: the absorbance, determined in
a 5-cm cell at the wavelength of 440 nm in a suitable spectrophotometer, methanol being used as the blank, is not greater
than 0.2.
Identification
A: Infrared Absorption 197K.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Loss on drying 731Dry it at 105 for 3 hours: it loses not
more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Chromatographic purity
Mobile phase, Standard preparation, Resolution solution, and
Chromatographic systemProceed as directed in the Assay.

Official from May 1, 2012

Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.

Accessed from 128.83.63.20 by nEwp0rt1 on Thu Nov 24 02:21:34 EST 2011

USP 35

Official Monographs / Felodipine 3155

Test preparationUse the Assay preparation.

ProcedureInject a volume (about 40 L) of the Test preparation into the chromatograph. Allow the Test preparation to
elute for not less than two times the retention time of
felodipine. Record the chromatograms, and measure the areas
for the impurity peaks. Calculate the per centage of each impurity in the portion of Felodipine taken by the formula:
100(ri / rs)
in which ri is the peak response for each impurity; and rs is the
sum of all the responses of all the peaks: not more than 1.0%
of any individual impurity is found, and the sum of all impurities is not more than 1.5%.
Assay
Mobile phaseDissolve 6.9 g of monobasic sodium phosphate in 400 mL of water in a 1-liter volumetric flask. Add 8.0
mL of 1 M phosphoric acid, dilute with water to volume, and
mix. Prepare a filtered and degassed mixture of this solution,
acetonitrile, and methanol (40:40:20). Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solutionDissolve 150 mg of Felodipine in a mixture of 25 mL of tertiar y butyl alcohol and 25 mL of 1 N perchloric acid, add 10 mL of 0.1 M ceric sulfate, mix, and allow
to stand for 15 minutes. Add 3.5 mL of 10 N sodium hydroxide, and neutralize with 2 N sodium hydroxide. Shake the mixture with 25 mL of methylene chloride in a separator. Draw off
the lower layer, and evaporate it to dr yness under a stream of
nitrogen on a water bath. Dissolve 10 mg of the residue
(felodipine oxidation product) and 5 mg of USP Felodipine RS
in Mobile phase, dilute with Mobile phase to 100 mL, and mix.
Transfer 1.0 mL of the resulting solution to a 100-mL volumetric
flask, dilute with Mobile phase to volume, and mix.
Standard preparationDissolve an accurately weighed quantity of USP Felodipine RS in Mobile phase, and quantitatively
dilute with Mobile phase to obtain a solution having a known
concentration of about 0.3 mg per mL. [ NOTEPrepare this solution fresh prior to analysis.]
Assay preparationTransfer an accurately weighed quantity
of about 30 mg of Felodipine to a 100-mL volumetric flask,
dissolve in and dilute with Mobile phase to volume, and mix.
[NOTEPrepare this solution fresh prior to analysis.]
Chromatographic system (see Chromatography 621)The
liquid chromatograph is equipped with a 254-nm detector and
a 4.6-mm 15-cm column that contains 5- m packing L1. The
flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for
Procedure: the capacity factor, k, is not less than 5.0; the column efficiency is not less than 1500 theoretical plates; and the
tailing factor is not greater than 1.5. Inject 20 L of the Resolution solution into the chromatograph, and adjust the sensitivity
of the system so that the heights of the two peaks in the chromatogram are not less than 20% of recorder full scale. The
resolution, R, between the first peak (felodipine oxidation product) and the second peak (felodipine) is not less than 2.5.
ProcedureSeparately inject equal volumes (about 40 L) of
the Standard preparation and the Assay preparation into the
chromatograph, record the chromatograms, and measure the
responses for the major peaks. Calculate the quantity, in mg, of
C18H19Cl2NO4 in the portion of Felodipine taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP
Felodipine RS in the Standard preparation; and rU and rS are the
peak responses obtained from the Assay preparation and the
Standard preparation, respectively.

Felodipine Extended-Release Tablets

.

DEFINITION
Felodipine Extended-Release Tablets contain NLT 90.0% and
NMT 110.0% of the labeled amount of felodipine
(C18H19Cl2NO4).
IDENTIFICATION
The retention time of the major peak from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
PROCEDURE
Solution A: 6.9 mg/mL of monobasic sodium phosphate in
water. Adjust with 1 M phosphoric acid to a pH of 3.0
0.05.
Mobile phase: Acetonitrile, methanol, and Solution A (2:1:2)
Standard stock solution: 2 mg/mL of USP Felodipine RS in
methanol
Standard solution: 0.02 mg/mL from the Standard stock solution in Mobile phase
Sample solution: Dissolve a quantity equivalent to 10 mg of
felodipine from powdered T ablets (NLT 10 Tablets), in 40
mL of acetonitrile and 20 mL of methanol in a 100-mL volumetric flask, and sonicate for 5 min. Add about 30 mL of
Solution A, and shake by mechanical means for 30 min. Allow the solution to cool to room temperature, and dilute
with Solution A to volume. Centrifuge a portion of the solution at high speed for 15 min. T ransfer 10 mL of the supernatant to a 50-mL volumetric flask, and dilute with Mobile
phase to volume. Pass a portion of this solution through a
filter having a 0.5- m or finer porosity, discarding the first 4
mL of the filtrate.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 362 nm
Column: 4.6-mm 15-cm; packing L1
Flow rate: 1 mL/min
Injection size: 40 L
System suitability
Sample: Standard solution
Suitability requirements
Column efficiency: NLT 1500 theoretical plates
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the per centage of C 18H19Cl2NO4 in the portion of
Tablets taken:
Result = (r U/rS) (C S/CU) 100
rU
rS
CS

= peak response from the Sample solution

= peak response from the Standard solution
= concentration of USP Felodipine RS in the
Standard solution (mg/mL)
= nominal concentration of felodipine in the
CU
Sample solution (mg/mL)
Acceptance criteria: 90.0%110.0%
PERFORMANCE TESTS
DISSOLUTION 711
Test 1
Medium: pH 6.5 phosphate buffer with 1% sodium laur yl
sulfate (Transfer 206 mL of 1 M monobasic sodium
phosphate monohydrate, 196 mL of 0.5 M anhydrous
dibasic sodium phosphate, and 50.0 g of sodium laur yl
sulfate to a 5000-mL volumetric flask. Add about 4000 mL
of water, and mix well. If necessar y, adjust with 1 N
sodium hydroxide to a pH of 6.5. Dilute with water to
volume.); 500 mL

Official from May 1, 2012

Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.