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 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)
[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 Compound 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 extraction starting with “heat at 50 in a water bath”. Transfer the supernatant to the volumetric flask containing the supernatant from the first extraction, dilute with methanol to volume, and mix.
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 extraction starting with “heat at 50 in a water bath”. Transfer the supernatant to the volumetric flask containing the supernatant from the first extraction, dilute with methanol to volume, and mix.
Chromatographic system
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. ]
Suitability requirements
Resolution:
NLT 2.0 between clotrimazole and clotrimazole 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.
and 30.
• Labeling:
Cream that is packaged and labeled for use as a vaginal preparation shall be labeled Clotrimazole Vaginal Cream.
• USP Reference Standards 
11
11
USP Clotrimazole RS 
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USP Clotrimazole Related Compound A RS
(o-Chlorophenyl)diphenylmethanol.
C19H15ClO 294.78
(o-Chlorophenyl)diphenylmethanol.
C19H15ClO 294.78
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison 1-301-816-8394 |
(SM12010) Monographs - Small Molecules 1 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2741
Pharmacopeial Forum: Volume No. 35(6) Page 1451