Accessed from 10.6.1.

1 by brunswick20 on Tue Feb 21 02:00:19 EST 2017

3524 Clorsulon / Official Monographs USP 40

Acceptance criteria 2 Suitability requirements

Any individual impurities: 0.5%; no spot other than Resolution: NLT 2.0 between clotrimazole and clo-
the principal spot of the Sample solution is larger or trimazole related compound A, System suitability
more intense than that of the principal spot of the solution
5-µL portion of Standard solution B. Relative standard deviation: NMT 2.0%, Standard
Total impurities: NMT 2.0% solution
Analysis
SPECIFIC TESTS Samples: Standard solution and Sample solution
• MELTING RANGE 〈741〉: 197°–203° Calculate the percentage of C22H17ClN2 in the portion
• LOSS ON DRYING 〈731〉 of Clotrimazole taken:
Analysis: Dry a sample under vacuum at 100° for 4 h.
Acceptance criteria: NMT 0.5% Result = (rU/rS) × (CS/CU) × 100
ADDITIONAL REQUIREMENTS rU = peak response of clotrimazole from the Sample
• PACKAGING AND STORAGE: Preserve in well-closed solution
containers. rS = peak response of clotrimazole from the
• LABELING: Label it to indicate that it is for veterinary use Standard solution
only. CS = concentration of USP Clotrimazole RS in the
• USP REFERENCE STANDARDS 〈11〉 Standard solution (mg/mL)
USP Clorsulon RS CU = concentration of Clotrimazole in the Sample
solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the dried basis
.

IMPURITIES
Clotrimazole Inorganic Impurities
• RESIDUE ON IGNITION 〈281〉: NMT 0.1%

Delete the following:

•• HEAVY METALS, Method II 〈231〉: NMT 10 ppm• (Official 1-
.

Jan-2018)
Organic Impurities
• PROCEDURE 1: LIMIT OF IMIDAZOLE
C22H17ClN2 344.84 Adsorbent: 0.25-mm layer of chromatographic silica
1H-Imidazole, 1-[(2-chlorophenyl)diphenylmethyl]-; gel mixture
1-(o-Chloro-α,α-diphenylbenzyl)imidazole [23593-75-1]. Standard solution: 500 µg/mL of USP Imidazole RS in
DEFINITION chloroform
USP Monographs

Clotrimazole contains NLT 98.0% and NMT 102.0% of
C22H17ClN2, calculated on the dried basis.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197M〉
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
ASSAY
• PROCEDURE
Buffer: 4.35 mg/mL of dibasic potassium phosphate
Mobile phase: Acetonitrile and Buffer (3:1). Pass
through a membrane filter having a 0.2-µm or finer
pore size. The ratio of volumes may be changed to ob-
tain the required resolution.
Standard solution: 0.5 mg/mL of USP Clotrimazole RS
in methanol
System suitability solution: 0.1 mg/mL each of USP
Clotrimazole RS and USP Clotrimazole Related Com-
pound A RS in methanol
Sample solution: 0.5 mg/mL of Clotrimazole in
methanol
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 254 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1.5 mL/min
Injection size: 25 µL
System suitability
Samples: Standard solution and System suitability
solution
[NOTE—The relative retention times for clotrimazole and
clotrimazole related compound A are 1.0 and 1.2,
respectively.]
Sample solution: 100 mg/mL of Clotrimazole in
chloroform
Application volume: 5 µL
Developing solvent system: Methanol and chloroform
(3:2)
Analysis
Samples: Standard solution and Sample solution
Proceed as directed for Chromatography 〈621〉, Thin-
Layer Chromatography. After air-drying the plate for
5 min, place it in a closed container with a dish
containing 100 g of iodine in a shallow layer, and
allow to remain for 60 min. Remove the plate from
the container, and observe the chromatogram.
Acceptance criteria: Any brown spot from the Sample
solution at an RF value corresponding to the principal
spot from the Standard solution is not greater in size or
intensity than the principal spot from the Standard so-
lution: NMT 0.5% of imidazole.
• PROCEDURE 2: LIMIT OF CLOTRIMAZOLE RELATED COMPOUND
A
Buffer, Mobile phase, System suitability solution, and
Chromatographic system: Proceed as directed in the
Assay.
Standard solution: 50 µg/mL of USP Clotrimazole Re-
lated Compound A RS prepared by dissolving in meth-
anol using about 75% of the final flask volume. Dilute
with Buffer to volume.
Sample solution: Transfer 100 mg of Clotrimazole to a
10-mL volumetric flask, add 5 mL of methanol to dis-
solve, add 2.5 mL of Buffer, dilute with methanol to
volume, and mix.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of clotrimazole related com-
pound A in the portion of Clotrimazole taken:
Result = (rU/rS) × (CS/CU) × 100

Official from null

Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 10.6.1.1 by brunswick20 on Tue Feb 21 02:00:19 EST 2017
USP 40
rU = peak response of clotrimazole related
compound A from the Sample solution
rS = peak response of clotrimazole related
compound A from the Standard solution
CS = concentration of the Standard solution
(mg/mL)
CU = concentration of the Sample solution (mg/mL)
Acceptance criteria: NMT 0.5%
SPECIFIC TESTS
• LOSS ON DRYING 〈731〉: Dry a sample at 105° for 2 h: it
loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers.
• USP REFERENCE STANDARDS 〈11〉
USP Clotrimazole RS
USP Clotrimazole Related Compound A RS
(o-Chlorophenyl)diphenylmethanol.
C19H15ClO 294.78
USP Imidazole RS
.
Clotrimazole Cream
DEFINITION
Clotrimazole Cream contains NLT 90.0% and NMT 110.0%
of the labeled amount of clotrimazole (C22H17ClN2).
IDENTIFICATION
• The retention time of the major peak of the Sample solu-
tion corresponds to that of the Standard solution, as ob-
tained in the Assay.
ASSAY
• PROCEDURE
Buffer: 4.35 mg/mL of dibasic potassium phosphate
Mobile phase: Acetonitrile and Buffer (3:1)
[NOTE—The ratio of volumes may be changed to obtain
the required resolution.]
Standard solution: 0.5 mg/mL of USP Clotrimazole RS
in methanol
System suitability solution: 0.1 mg/mL each of USP
Clotrimazole RS and USP Clotrimazole Related Com-
pound A RS in methanol
Sample solution: Transfer the equivalent of 25 mg of
clotrimazole from the Cream to a 50-mL screw-capped
centrifuge tube. Add 25.0 mL of methanol, and heat at
50° in a water bath for 5 min, with occasional shaking.
Remove the tube from the bath, and shake vigorously
for 5 min. Cool in a methanol–ice bath for 15 min, and
promptly centrifuge. Transfer the supernatant to a
50-mL volumetric flask. Add 20.0 mL of methanol to
the residue in the centrifuge tube, and repeat the ex-
traction starting with “heat at 50° in a water bath”.
Transfer the supernatant to the volumetric flask contain-
ing the supernatant from the first extraction, dilute with
methanol to volume, and mix.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 254 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1.5 mL/min
Injection size: 25 µL
System suitability
Samples: Standard solution and System suitability
solution
[NOTE—The relative retention times for clotrimazole and
clotrimazole related compound A are 1.0 and 1.2,
respectively.]
Official from null
Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Clotrimazole 3525
Suitability requirements
Resolution: NLT 2.0 between clotrimazole and clo-
trimazole related compound A, System suitability
solution
Relative standard deviation: NMT 2.0%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of C22H17ClN2 in the portion
of Cream taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of clotrimazole from the Sample
solution
rS = peak response of clotrimazole from the
Standard solution
CS = concentration of USP Clotrimazole RS in the
Standard solution (mg/mL)
CU = nominal concentration of clotrimazole in the
Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in collapsible tubes or
tight containers, at a temperature between 2° and 30°.
• LABELING: Cream that is packaged and labeled for use as
a vaginal preparation shall be labeled Clotrimazole Vagi-
nal Cream.
• USP REFERENCE STANDARDS 〈11〉
USP Clotrimazole RS
USP Clotrimazole Related Compound A RS
(o-Chlorophenyl)diphenylmethanol.
C19H15ClO 294.78
USP Monographs
.
Clotrimazole Lotion
DEFINITION
Clotrimazole Lotion contains NLT 90.0% and NMT 110.0%
of the labeled amount of clotrimazole (C22H17ClN2).
IDENTIFICATION
• A. The retention time of the major peak for clotrimazole
of the Sample solution corresponds to that of the Stan-
dard solution, as obtained in the Assay.
ASSAY
• PROCEDURE
Buffer: 4.35 g/L of dibasic potassium phosphate in
water
Mobile phase: Methanol and Buffer (3:1). Pass through
a filter of 0.5-µm or finer pore size.
Internal standard solution: 0.07 mg/mL of testoster-
one propionate in dehydrated alcohol
Standard stock solution A: 2 mg/mL of USP Clo-
trimazole RS in dehydrated alcohol
Standard stock solution B: 0.1 mg/mL of USP Clo-
trimazole Related Compound A RS in dehydrated
alcohol
Standard solution: Standard stock solution A, Standard
stock solution B, and Internal standard solution
(5.0: 5.0: 10.0)
Sample solution: Nominally 1 mg/mL, prepared as fol-
lows. Transfer the equivalent of 10 mg of clotrimazole
from freshly mixed Lotion to a screw-capped, 50-mL
centrifuge tube. Add 10.0 mL of Internal standard solu-
tion, place the cap on the tube, and heat at 50° in a
water bath for 5 min, with occasional shaking. Remove
the tube from the bath, and shake vigorously for 5 min.
Cool in a methanol–ice bath for 15 min, and promptly
centrifuge. Transfer the supernatant to a test tube. Add
10.0 mL of dehydrated alcohol to the residue in the