Clotrimazole Topical Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
DOWNLOAD PDF HERE

1 DEFINITION

Clotrimazole Topical Solution is a solution of Clotrimazole in a suitable nonaqueous, hydrophilic solvent. It contains NLT 90.0% and NMT 115.0% of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂).

2 IDENTIFICATION

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

B. The UV spectrum of the clotrimazole peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Buffer: 0.3 g/L of monobasic sodium phosphate, anhydrous and 0.35 g/L of dibasic sodium phosphate, anhydrous in water. The resulting solution has a pH of 6.6-7.0.

Mobile phase: Acetonitrile and Buffer (50:50)

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.2 mg/mL of USP Clotrimazole RS in Diluent

Sample solution: Nominally equivalent to 0.2 mg/mL of clotrimazole from Topical Solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 206 nm. For Identification test B, use a diode array detector in the range of 200-300 nm.

Column: 4.6-mm × 15-cm; 5-µm packing L85

Flow rate: 1 mL/min

Injection volume: 8 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

FICIAL

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) in the portion of Topical Solution taken:

Result = (r_u/r_s) × (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%-115.0%

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Buffer, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.001 mg/mL each of USP Clotrimazole RS, USP Imidazole RS, and USP Clotrimazole Related Compound A RS in Diluent

System suitability

Sample: Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 4 between imidazole and clotrimazole related compound A, and between clotrimazole and clotrimazole related compound A

Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of clotrimazole related compound A and imidazole in the portion of Topical Solution taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clotrimazole related compound A or imidazole from the Sample solution

r_s = peak response of clotrimazole related compound A or imidazole from the Standard solution

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

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

Calculate the percentage of any unspecified impurity in the portion of Topical Solution taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each unspecified impurity from the Sample solution Γυ

r_s = peak response of the clotrimazole from the Standard solution s

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: See Table 1. Disregard any impurity peak less than 0.05%.

Table 1

5 ADDITIONAL REQUIREMENTS

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

5.2 USP REFERENCE STANDARDS (11)

USP Clotrimazole RS

USP Clotrimazole Related Compound A.RS

(o-Chlorophenyl) diphenylmethanol.

C₁₉H₁₅CIO 294.78

USP Imidazole RS C₃H₄C₂ 68.08