Clobetasol Propionate 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)

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1 DEFINITION

Clobetasol Propionate Topical Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of clobetasol propionate (C₂₅H₃₂ClFO₅).

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 0.75 mg/mL of USP Clobetasol Propionate RS in chloroform

Test solution: Nominally 0.75 mg/mL of clobetasol propionate. Transfer a portion of Topical Solution equivalent to 1.5 mg of clobetasol to a 50-mL separatory funnel. Add 5 mL of water, and extract with 5 mL of chloroform. Collect the lower layer through a cotton wool plug, and evaporate with the aid of a stream of nitrogen to dryness. Dissolve the residue in 2 mL of chloroform.

Developing solvent system: Chloroform, acetone, and alcohol (100:10:5)

Acceptance criteria: The Rf value of the principal spot obtained from the Test solution corresponds to that from the Standard solution.

3 ASSAY

3.1 Procedure

Buffer: 0.05 M monobasic sodium phosphate. Adjust with 85% phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile, methanol, and Buffer (95:20:85)

Internal standard solution: 0.2 mg/mL of beclomethasone dipropionate in methanol

System suitability solution: 0.001 mg/mL of USP Clobetasol Propionate Related Compound A RS and 0.1 mg/mL of USP Clobetasol Propionate RS in Mobile phase

Standard solution: 0.04 mg/mL of USP Clobetasol Propionate RS and 0.08 mg/mL of beclomethasone dipropionate prepared as follows. Transfer 1.0 mg of USP Clobetasol Propionate RS to a 25-mL volumetric flask, add 10.0 mL of the Internal standard solution, and dilute with methanol to volume.

Sample solution: Nominally 0.04 mg/mL of clobetasol propionate. Transfer a portion of Topical Solution equivalent to 1.0 mg of clobetasol propionate to a 25-mL volumetric flask, add 10.0 mL of the Internal standard solution, and dilute with Mobile phase to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 240 nm
• Column: 4.6-mm × 15-cm; packing L1
• Flow rate: 1 mL/min
• Injection size: 10 µL

System suitability

• Sample: System suitability solution
• [Note-The relative retention times for clobetasol propionate and clobetasol propionate related compound A are 1.0 and 1.1, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between clobetasol propionate and clobetasol propionate related compound A
• Column efficiency: NLT 5000 theoretical plates for the clobetasol propionate peak
• Tailing factor: NMT 2.0 for the clobetasol propionate peak
• Relative standard deviation: NMT 2.0% for the clobetasol propionate peak

Analysis

Samples: Standard solution and Sample solution

[Note-The relative retention times for clobetasol propionate and beclomethasone dipropionate are 1.0 and 1.6, respectively.]

Calculate the percentage of clobetasol propionate (C₂₅H₃₂ClFO₅) in the portion of Topical Solution taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = ratio of the clobetasol propionate peak area to the internal standard peak area from the Sample solution

R_s = ratio of the clobetasol propionate peak area to the Internal standard peak area from the Standard solution

C_s = concentration of USP Clobetasol Propionate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Minimum Fill 〈755〉: Meets the requirements

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/g. It meets the requirements of the tests for absence of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella species.

pH 〈791〉: 4.5-6.0

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature. Do not refrigerate.

USP Reference Standards 〈11〉

• USP Clobetasol Propionate RS
• USP Clobetasol Propionate Related Compound A RS

9α-Fluoro-11β-hydroxy-16β-methyl 3-oxo-androsta-1,4-diene-17(R)-spiro-2′-[4′-chloro-5′-ethylfuran-3′(2′H)-one].

C₂₅H₃₀ClFO₄ 448.96