Clotrimazole Vaginal Inserts

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 Vaginal Inserts contain NLT 90.0% and NMT 110.0% 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 major 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 anhydrous monobasic sodium phosphate and 0.35 g/L of anhydrous dibasic sodium phosphate in water. The resulting solution has a pH of 6.6-7.0.

Mobile phase: Acetonitrile and Buffer (1:1)

Diluent: Acetonitrile and water (1:1)

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

Sample solution: Nominally 0.2 mg/mL of clotrimazole in Diluent prepared as follows. Transfer a portion of powdered Vaginal Inserts (from NLT 20 Vaginal Inserts) equivalent to 5 mg of clotrimazole to a 25-mL volumetric flask. Dilute with Diluent to volume. Sonicate for about 10 min, and centrifuge at 3500 rpm for about 15 min at ambient temperature to obtain a clear supernatant. Use the clear supernatant for injection.

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 200-400 nm.

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

Flow rate: 1 mL/min

Injection volume: 8 µL

Run time: 1.25 times the retention time of clotrimazole

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) in the portion of Vaginal Inserts 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%-110.0%

4 PERFORMANCE TESTS

4.1 DISINTEGRATION (701).

Time: 20 min

Acceptance criteria: Meet the requirements

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

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

Standard solution: 1 µg/mL each of USP Clotrimazole RS, USP Clotrimazole Related Compound A RS, and USP Imidazole RS in Diluent

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 4.0 between clotrimazole related compound A and imidazole peaks; NLT 4.0 between clotrimazole and clotrimazole related compound A peaks

Relative standard deviation: NMT 2.0% for clotrimazole, clotrimazole related compound A, and imidazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity in the portion of Vaginal Inserts taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of the corresponding specified impurity from the Sample solution

r_s = peak response of the corresponding specified impurity from the Standard solution s

C_s = concentration of the corresponding USP Reference Standard 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 Vaginal Inserts taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of any unspecified impurity from the Sample solution

r_s = peak response of 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

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE: Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Clotrimazole RS

USP Clotrimazole Related Compound A RS

(o-Chlorophenyl) diphenylmethanol.

C₁₉H₁₅CIO   294.78

USP Imidazole RS