Clotrimazole Cream

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Clotrimazole Cream contains NLT 90.0% and NMT 110.0% of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂).

2 IDENTIFICATION

The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 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.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection size: 25 µL

3.1.2 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.]

3.1.3 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.]

3.1.4 Suitability requirements

Resolution: NLT 2.0 between clotrimazole and clotrimazole related compound A, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.1.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂H,CIN, in the portion of Cream taken: 17

                Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of clotrimazole from the Sample solution

r_S = peak response of clotrimazole from the Standard solution

C_S = concentration of USP Clotrimazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of clotrimazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 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 Vaginal Cream.

USP REFERENCE STANDARDS (11)

USP Clotrimazole RS

USP Clotrimazole Related Compound A RS

(o-Chlorophenyl)diphenylmethanol.

C₁₉H₁₅ClO            294.78