Halobetasol 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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C₂₅H₃₁CIF₂O₅ 484.96

Pregna-1,4-diene-3,20-dione, 21-chloro-6,9-difluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-, (6α,11β,16β)-;

21-Chloro-6α,9-difluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate CAS RN^®: 66852-54-8; UNII: 91A0K1TY3Z.

1 DEFINITION

Halobetasol Propionate contains NLT 98.0% and NMT 102.0% of halobetasol propionate (C₂₅H₃₁CIF₂O₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy : 197K

B. The retention time 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

Solution A: Acetonitrile and water (90:110)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 0.2 mg/mL of USP Halobetasol Propionate RS in acetonitrile

Sample solution: 0.2 mg/mL of Halobetasol Propionate in acetonitrile

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 20 µL

3.3 System suitability

Sample: Standard solution

Tailing factor: 0.9-1.1

Suitability requirements

Relative standard deviation: NMT 0.73%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of halobetasol propionate (C₂₅H₃₁CIF₂O₅) in the portion of Halobetasol Propionate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of halobetasol propionate from the Sample solution

r_S = peak response of halobetasol propionate from the Standard solution

C_S = concentration of USP Halobetasol Propionate RS in the Standard solution (mg/mL)

C_U = concentration of Halobetasol Propionate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Mobile phase, Standard solution, and Sample solution: Prepare as directed in the Assay.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 15,000 theoretical plates

Tailing factor: 0.9-1.1

Relative standard deviation: NMT 0.73%

Analysis

Sample: Sample solution

Calculate the percentage of any impurity in the portion of Halobetasol Propionate taken:

Result = (r_U/r_T) x 100

r_U = peak response of any individual impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 2.

Table 2

^a 21-Chloro-6α,9-difluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione.

^b 6α,9-Difluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 21-acetate 17-propionate.

^c 21-Chloro-6α,9-difluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 11-propionate.

^d 9,21-Dichloro-6α,-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate.

^e 6α,21-Dichloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate.

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry a sample under vacuum at 105° for 3 h.

Acceptance criteria: NMT 1.0%

5.2 OPTICAL ROTATION, Specific Rotation(781S).

Sample solution: 10 mg/mL in dioxane

Acceptance criteria: +87° to +99°

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed, light-resistant containers. Store between 2° and 8°.

6.2 USP REFERENCE STANDARDS (11)

USP Halobetasol Propionate RS