Clobetasol Propionate

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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C₂₅H₃₂ClFO₅ 466.97

Pregna-1,4-diene-3,20-dione, 21-chloro-9-fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-, (11β,16β)-;

21-Chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate

CAS RN®: 25122-46-7; UNII: 779619577M.

CAS RN®: 25122-41-2; UNII: ADN79D536H.

1 DEFINITION

Clobetasol Propionate contains NLT 97.0% and NMT 102.0% of C₂₅H₃₂ClFO₅, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

3 ASSAY

3.1 Procedure

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

Mobile phase: Acetonitrile, methanol, and Solution A (19:4:17)

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

Standard solution: Dissolve a quantity of USP Clobetasol Propionate RS in methanol and Internal standard solution to obtain a final solution of 0.04 mg/mL of USP Clobetasol Propionate RS and 0.08 mg/mL of beclomethasone dipropionate.

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

Sample solution: Transfer 4 mg of Clobetasol Propionate to a 100-mL volumetric flask, add 40.0 mL of Internal standard solution, and dilute with methanol 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%

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 C₂₅H₃₂ClFO₅ in the portion of Clobetasol Propionate 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: 97.0%–102.0% on the dried basis

4 IMPURITIES

4.1 Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%, using a platinum crucible

4.2 Organic Impurities

4.2.1 Procedure

Solution A, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Sample solution: 0.1 mg/mL of Clobetasol Propionate in Mobile phase

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Clobetasol Propionate taken:

Result = (r_u/r_T) × 100

r_u = peak area for each impurity

r_T = sum of the areas of all of the peaks

Acceptance criteria

• Any individual impurity: NMT 1.0%
• Total impurities: NMT 2.5%

5 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: Approximately 196°

Optical Rotation, Specific Rotation 〈781S〉: +98° to +104° at 20°

Sample solution: 10 mg/mL in dioxane

Loss on Drying 〈731〉: Dry a sample at 105° for 3 h: it loses NMT 2.0% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

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