1122 Ketoconazole Cream / Official Monographs
Operating conditions—
Detector: An ultraviolet absorption photometer (wave-
length: 220 nm).
Column: A stainless steel column 4.6 mm in inside diame-
ter and 10 cm in length, packed with octadecylsilanized silica
gel for liquid chromatography (3 mm in particle diameter).
Column temperature: A constant temperature of about
259 C.
Mobile phase A: Acetonitrile for liquid chromatography.
Mobile phase B: A solution of tetrabutylammonium
hydrogensulfate (17 in 5000).
Flowing of mobile phase: Control the gradient by mixing
the mobile phases A and B as directed in the following table.
Time after injection Mobile phase A Mobile phase B
of sample (min) (volz) (volz)
0 – 10 5 → 50 95 → 50
10 – 15 50 50
Flow rate: 2.0 mL per minute.
Time span of measurement: For 15 minutes after injec-
tion, beginning after the solvent peak.
System suitability—
Test for required detectability: Pipet 2 mL of the standard
solution, and add methanol to make exactly 20 mL. Confirm
that the peak area of ketoconazole obtained from 10 mL of
this solution is equivalent to 7 to 13z of that of ketocona-
zole obtained from 10 mL of the standard solution.
System performance: When the procedure is run with 10
mL of the standard solution under the above operating con-
ditions, the number of theoretical plates and the symmetry
factor of the peak of ketoconazole are not less than 40,000
and not more than 1.5, respectively.
System repeatability: When the test is repeated 6 times
with 10 mL of the standard solution under the above operat-
ing conditions, the relative standard deviation of the peak
area of ketoconazole is not more than 2.5z.
Loss on drying <2.41> Not more than 0.5z (1 g, 1059C,
4 hours).
Residue on ignition <2.44> Not more than 0.1z (1 g).
Assay Weigh accurately about 0.2 g of Ketoconazole, pre-
viously dried, dissolve in 70 mL of a mixture of 2-butanone
and acetic acid (100) (7:1), and titrate <2.50> with 0.1 mol/L
perchloric acid VS (potentiometric titration). Perform a
blank determination in the same manner, and make any nec-
essary correction.
Each mL of 0.1 mol/L perchloric acid VS
＝ 26.57 mg of C26H28Cl2N4O4
Containers and storage Containers—Tight containers.
Storage—Light-resistant.
Ketoconazole Cream
ケトコナゾールクリーム
Ketoconazole Cream contains not less than 95.0z
and not more than 105.0z of the labeled amount of
ketoconazole (C26H28Cl2N4O4: 531.43).
Method of preparation Prepare as directed under Creams,
with Ketoconazole.
JP XVII
Identification To a quantity of Ketoconazole Cream,
equivalent to 0.1 g of Ketoconazole, add 20 mL of 2-
propanol, shake for 20 minutes, centrifuge, and use the su-
pernatant liquid as the sample solution. Separately, dissolve
25 mg of ketoconazole in 5 mL of 2-propanol, and use this
solution as the standard solution. Perform the test with these
solutions as directed under Thin-layer Chromatography
<2.03>. Spot 5 mL each of the sample solution and standard
solution on a plate of silica gel with fluorescent indicator for
thin-layer chromatography. Develop the plate with a mixture
of ethyl acetate, hexane, methanol, water and ammonia so-
lution (28) (40:40:25:2:1) to a distance of about 12 cm, and
air-dry the plate. Examine under ultraviolet light (main
wavelength: 254 nm): the principal spot obtained from the
sample solution has the same R f value as the spot obtained
from the standard solution.
Assay Weigh accurately an amount of Ketoconazole
Cream, equivalent to about 25 mg of ketoconazole
(C26H28Cl2N4O4), dissolve in methanol to make exactly 100
mL. Pipet 10 mL of this solution, add exactly 4 mL of the
internal standard solution, add methanol to make 50 mL,
and use this solution as the sample solution. Separately,
weigh accurately about 25 mg of ketoconazole for assay,
previously dried at 1059C for 4 hours, and dissolve in metha-
nol to make exactly 50 mL. Pipet 5 mL of this solution, add
exactly 4 mL of the internal standard solution, add methanol
to make 50 mL, and use this solution as the standard solu-
tion. Perform the test with 10 mL each of the sample solution
and standard solution as directed under Liquid Chromatog-
raphy <2.01> according to the following conditions, and cal-
culate the ratios, QT and QS, of the peak area of ketocona-
zole to that of the internal standard.
Amount (mg) of ketoconazole (C26H28Cl2N4O4)
＝ MS × QT/QS
MS: Amount (mg) of ketoconazole for assay taken
Internal standard solution—A solution of xanthone in meth-
anol (1 in 10,000).
Operating conditions—
Detector: An ultraviolet absorption photometer (wave-
length: 230 nm).
Column: A stainless steel column 4.6 mm in inside diame-
ter and 15 cm in length, packed with octadecylsilanized silica
gel for liquid chromatography (5 mm in particle diameter).
Column temperature: A constant temperature of about
409C.
Mobile phase: To ammonium acetate solution (1 in 200)
add acetic acid (100) to adjust the pH to 5.0. To 250 mL of
this solution add 750 mL of methanol.
Flow rate: Adjust so that the retention time of ketocona-
zole is about 8 minutes.
System suitability—
System performance: When the procedure is run with 10
mL of the standard solution under the above operating con-
ditions, the internal standard and ketoconazole are eluted in
this order with the resolution between these peaks being not
less than 5.
System repeatability: When the test is repeated 6 times
with 10 mL of the standard solution under the above operat-
ing conditions, the relative standard deviation of the ratio of
the peak area of ketoconazole to that of the internal stand-
ard is not more than 1.0z.
Containers and storage Containers—Tight containers.
JP XVII
Ketoconazole Lotion
ケトコナゾールローション
Ketoconazole Lotion is an emulsion lotion.
It contains not less than 93.0z and not more
than 107.0z of the labeled amount of ketoconazole
(C26H28Cl2N4O4: 531.43).
Method of preparation Prepare as directed under Lotions,
with Ketoconazole.
Description Ketoconazole Lotion occurs as a white emul-
sion.
Identification Shake well and take an amount of Ketocona-
zole Lotion, equivalent to 0.1 g of Ketoconazole, add 20 mL
of 2-propanol, shake for 20 minutes, centrifuge, and use the
supernatant liquid as the sample solution. Separately, dis-
solve 25 mg of ketoconazole in 5 mL of 2-propanol, and use
this solution as the standard solution. Perform the test with
these solutions as directed under Thin-layer Chromatogra-
phy <2.03>. Spot 5 mL each of the sample solution and stand-
ard solution on a plate of silica gel with fluorescent indicator
for thin-layer chromatography. Develop the plate with a
mixture of ethyl acetate, hexane, methanol, water and am-
monia solution (28) (40:40:25:2:1) to a distance of about 12
cm, and air-dry the plate. Examine under ultraviolet light
(main wavelength: 254 nm): the principal spot obtained from
the sample solution has the same R f value as the spot ob-
tained from the standard solution.
Assay Shake well and weigh accurately an amount of Keto-
conazole Lotion, equivalent to about 25 mg of ketoconazole
(C26H28Cl2N4O4), dissolve in methanol to make exactly 100
mL. Pipet 10 mL of this solution, add exactly 4 mL of the
internal standard solution, add methanol to make 50 mL,
and use this solution as the sample solution. Separately,
weigh accurately about 25 mg of ketoconazole for assay,
previously dried at 1059C for 4 hours, dissolve in methanol
to make exactly 50 mL. Pipet 5 mL of this solution, add ex-
actly 4 mL of the internal standard solution, add methanol
to make 50 mL, and use this solution as the standard solu-
tion. Perform the test with 10 mL each of the sample solution
and standard solution as directed under Liquid Chromatog-
raphy <2.01> according to the following conditions, and cal-
culate the ratios, QT and QS, of the peak area of ketocona-
zole to that of the internal standard.
Amount (mg) of ketoconazole (C26H28Cl2N4O4)
＝ M S × QT / QS
MS: Amount (mg) of ketoconazole for assay taken
Internal standard solution—A solution of xanthone in meth-
anol (1 in 10,000).
Operating conditions—
Detector: An ultraviolet absorption photometer (wave-
length: 230 nm).
Column: A stainless steel column 4.6 mm in inside diame-
ter and 15 cm in length, packed with octadecylsilanized silica
gel for liquid chromatography (5 mm in particle diameter).
Column temperature: A constant temperature of about
409 C.
Mobile phase: To ammonium acetate solution (1 in 200)
add acetic acid (100) to adjust the pH to 5.0. To 250 mL of
this solution add 750 mL of methanol.
Flow rate: Adjust so that the retention time of ketocona-
zole is about 8 minutes.
Official Monographs / Ketoconazole Solution 1123
System suitability—
System performance: When the procedure is run with 10
mL of the standard solution under the above operating con-
ditions, the internal standard and ketoconazole are eluted in
this order with the resolution between these peaks being not
less than 5.
System repeatability: When the test is repeated 6 times
with 10 mL of the standard solution under the above operat-
ing conditions, the relative standard deviation of the ratio of
the peak area of ketoconazole to that of the internal stand-
ard is not more than 1.0z.
Containers and storage Containers—Tight containers.
Ketoconazole Solution
ケトコナゾール液
Ketoconazole Solution is a liquid for external use.
Ketoconazole Solution contains not less than 95.0z
and not more than 105.0z of the labeled amount of
ketoconazole (C26H28Cl2N4O4: 531.43).
Method of preparation Prepare as directed under Liquids
and Solutions for Cutaneous Application, with Ketocona-
zole.
Description Ketoconazole Solution is a clear liquid.
Identification To a volume of Ketoconazole Solution,
equivalent to 10 mg of Ketoconazole, add methanol to make
10 mL, and use this solution as the sample solution. Sepa-
rately, dissolve 10 mg of ketoconazole in 10 mL of metha-
nol, and use this solution as the standard solution. Perform
the test with these solutions as directed under Thin-layer
Chromatography <2.03>. Spot 5 mL each of the sample solu-
tion and standard solution on a plate of silica gel with fluo-
rescent indicator for thin-layer chromatography. Develop
the plate with a mixture of ethyl acetate, hexane, methanol,
water and ammonia solution (28) (40:40:30:2:1) to a distance
of about 10 cm, and air-dry the plate. Examine under ultra-
violet light (main wavelength: 254 nm): the principal spot
obtained from the sample solution has the same R f value as
the spot obtained from the standard solution.
pH Being specified separately when the drug is granted ap-
proval based on the Law.
Assay To an exact amount of Ketoconazole Solution,
equivalent to about 10 mg of ketoconazole (C26H28Cl2N4O4),
add exactly 5 mL of the internal standard solution, and add
15 mL of methanol. To 1 mL of this solution add methanol
to make 25 mL, and use this solution as the sample solution.
Separately, weigh accurately about 50 mg of ketoconazole
for assay, previously dried at 1059C for 4 hours, and dis-
solve in methanol to make exactly 50 mL. Pipet 10 mL of
this solution, add exactly 5 mL of the internal standard solu-
tion, add methanol to make 20 mL. Take 1 mL of this solu-
tion, add methanol to make 25 mL, and use this solution as
the standard solution. Perform the test with 20 mL each of
the sample solution and standard solution as directed under
Liquid Chromatography <2.01> according to the following
conditions, and calculate the ratios, QT and QS, of the peak
area of ketoconazole to that of the internal standard.
Amount (mg) of ketoconazole (C26H28Cl2N4O4)
＝ MS × QT/QS × 1/5
MS: Amount (mg) of ketoconazole for assay taken