Clotrimazole Lotion

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

2 IDENTIFICATION

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

3 ASSAY

3.1 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 Testosterone propionate in dehydrated alcohol

Standard stock solution A: 2 mg/mL of USP Clotrimazole RS in dehydrated alcohol

Standard stock solution B: 0.1 mg/mL of USP Clotrimazole 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 follows. 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 solution, 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 centrifuge tube, and repeat the extraction as directed above, beginning with "place the cap on the tube". Transfer the supernatant to the test tube containing the supernatant from the first extraction.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Columns

Guard: 2.1-mm x 6-cm, 10-µm packing L2

Analytical: 3.9-mm x 30-cm; 10-µm packing L1

Flow rate: 1 mL/min.

Injection volume: 20 µL

3.1.2 System suitability

Sample: Standard solution

[NOTE-The relative retention times for clotrimazole related compound A, clotrimazole, and testosterone propionate are 0.9, 1.0, and 1.5, respectively.]

3.1.3 Suitability requirements

Resolution: NLT 1.2 between clotrimazole related compound A and clotrimazole, and NLT 1.9 between clotrimazole and testosterone. propionate

Relative standard deviation: NMT 2.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount clotrimazole (C₂H₂, CIN₂) in the portion of Lotion taken:

                Result = (R_U/R_S) x (C_S/C_U) × 100

R_U = peak response ratio of clotrimazole to testosterone propionate from the Sample solution

R_S = peak response ratio of clotrimazole to testosterone propionate 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 IMPURITIES

ORGANIC IMPURITIES: LIMIT OF CLOTRIMAZOLE RELATED COMPOUND A

Analysis: Using the chromatograms of the Standard solution and Sample solution as obtained in the Assay, calculate the percentage of clotrimazole related compound A in the portion of Lotion taken:

                Result = (R_U/R_S) x (C_S/C_U) × 100

R_U = peak response ratio of clotrimazole related compound A to testosterone propionate from the Sample solution

R_S = peak response ratio of clotrimazole related compound A to testosterone propionate from the Standard solution

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

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

Acceptance criteria: NMT 5%

5 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): It meets the requirements for absence of Staphylococcus aureus and Pseudomonas aeruginosa.

PH (791): 5.0-7.0

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at a temperature between 2° and 30°.

USP REFERENCE STANDARDS (11)

USP Clotrimazole RS

USP Clotrimazole Related Compound A RS

(o-Chlorophenyl)diphenylmethanol.

C₁₉H₁₅ClO              294.78