Butoconazole Nitrate Vaginal 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

Butoconazole Nitrate Vaginal Cream contains Butoconazole Nitrate in a suitable cream base. It contains NLT 90.0% and NMT 110.0% of the labeled amount of butoconazole nitrate (C₁₉H₁₇Cl₃N₂S . HNO₃).

2 IDENTIFICATION

A.

Sample solution: Prepare a mixture of the Standard solution and the Sample solution (1:1), as directed in the Assay.

Analysis: Chromatograph the Sample solution, as directed in the Assay.

Acceptance criteria: The chromatogram exhibits two main peaks that correspond to butoconazole nitrate and the internal standard.

3 ASSAY

3.1 PROCEDURE

Buffer: 1.4 g of potassium acetate in 980 mL of water. Adjust with about 2 mL of glacial acetic acid to a pH of 4.3 ± 0.1, dilute with water to 1000 mL. Adjust the buffer molarity (0.018–0.072 M) as necessary to obtain suitable chromatographic performance. Increased retention time may be achieved by a decrease in the buffer molarity.

Diluent: Methanol and Buffer (60:40)

Mobile phase: Methanol and Buffer (65:35)

Internal standard solution: 1.6 mg/mL of 1-benzylimidazole in methanol

Standard stock solution: 0.4 mg/mL of USP Butoconazole Nitrate RS in methanol

Standard solution: Transfer 2.0 mL of the Standard stock solution and 3.0 mL of the Internal standard solution to a 50-mL flask, and add 35.0 mL of Diluent.

Sample stock solution: Nominally 0.4 mg/mL of butoconazole nitrate in methanol from Vaginal Cream prepared as follows. Add 200 mL of methanol to a 250-mL volumetric flask. Transfer to the flask a weighed quantity of Vaginal Cream equivalent to about 100 mg of butoconazole nitrate. Sonicate to dissolve, and cool to room temperature. Dilute with methanol to volume.

Sample solution: Transfer 2.0 mL of the Sample stock solution and 3.0 mL of the Internal standard solution to a 50-mL flask, and add 35.0 mL of Diluent. Allow the precipitated excipients that form to rise to the top of the solution, remove them by aspiration, and discard. Centrifuge or filter the remaining solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; packing L9 that has been converted to the potassium form by the use of 0.555 M potassium acetate solution

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for butoconazole nitrate and 1-benzylimidazole are 0.6 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between the analyte and internal standard peaks

Column efficiency: NLT 1100 theoretical plates for the analyte peak

Tailing factor: NMT 2.1 for the analyte peak

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of butoconazole nitrate (C₁₉H₁₇Cl₃N₂S . HNO₃) in the portion of Vaginal Cream taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak response ratio of butoconazole nitrate to the internal standard from the Sample solution

R_S = peak response ratio of butoconazole nitrate to the internal standard from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0% of the labeled amount

4 PERFORMANCE TESTS

MINIMUM FILL (755): Meets the requirements

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in collapsible tubes or tight containers. Avoid excessive heat, and avoid freezing.

USP REFERENCE STANDARDS (11)

USP Butoconazole Nitrate RS