Alclometasone Dipropionate

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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C₂₈H₃₇ClO₇  521.04

Pregna-1,4-diene-3,20-dione, 7-chloro-11-hydroxy-16-methyl-17,21-bis(1-oxopropoxy)-, (7α,11β,16α)-;

7α-Chloro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate CAS RN®: 66734-13-2; UNII: S56PQL4N1V.

1 DEFINITION

Alclometasone Dipropionate contains NLT 97.0% and NMT 102.0% of C₂₈H₃₇ClO₇, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, both relative to the Internal standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 6.80 mg/mL of monobasic potassium phosphate (0.05 M)

Mobile phase: Methanol and Solution A (2:1)

Internal standard solution: 2 mg/mL of betamethasone dipropionate in methanol

Standard stock solution: 1.2 mg/mL of USP Alclometasone Dipropionate RS in methanol

Standard solution: 4.0 mL of Standard stock solution and 4.0 mL of Internal standard solution. Dilute with methanol to 25 mL. [Note—This solution contains approximately 0.2 mg/mL of USP Alclometasone Dipropionate RS.]

Sample stock solution: 1.2 mg/mL of Alclometasone Dipropionate in methanol

Sample solution: 4 mL of Sample stock solution and 4 mL of Internal standard solution. Dilute with methanol to 25 mL. Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L1

Flow rate: 1.2 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for alclometasone dipropionate and betamethasone dipropionate are about 0.7 and 1.0, respectively.] Suitability requirements

Resolution: NLT 3.0 between the analyte and the internal standard peaks

Relative standard deviation: NMT 2%

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₈H₃₇ClO₇ in the portion of Alclometasone Dipropionate taken:

Result = (R_U /R_S ) × (C_S /C_U ) × 100

R_U = peak height ratio from the Sample solution  

R_S = peak height ratio from the Standard solution

C_S = concentration of USP Alclometasone Dipropionate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 97.0%–102.0% on the dried basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Mobile phase: Acetonitrile and water (3:2)

Diluent: Acetonitrile and water (2:1)

System suitability solution: 1.5 mg/mL of USP Alclometasone Dipropionate RS and 0.015 mg/mL of USP Alclometasone Dipropionate Related Compound A RS in Diluent

Sample solution: 1.5 mg/mL of Alclometasone Dipropionate in Diluent

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 5 µL

Run time: Three times the retention time of alclometasone

System suitability

Sample: System suitability solution

Suitability requirements

Tailing factor: NMT 1.5 for alclometasone dipropionate

Relative standard deviation: NMT 2.0% for alclometasone dipropionate

Resolution: NLT 2.0 between alclometasone dipropionate and alclometasone dipropionate related compound A

4.2 Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Alclometasone Dipropionate taken:

Result = (r_U /r_T ) × (1/F) × 100

r_U = peak area for each impurity from the Sample solution  

r_T = sum of all the peaks from the Sample solution  

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 2.0%

Impurity Table 1

a 11β,17,21-Trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate.

b 2-Bromo-7α-chloro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate.

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 30 mg/mL in dioxane

Acceptance criteria: +21° to +25°

Loss on Drying 〈731〉: Dry a sample in a vacuum at a pressure not exceeding 5 mm of mercury at 105° for 3 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Alclometasone Dipropionate RS

USP Alclometasone Dipropionate Related Compound A RS

11β,17,21-Trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate.

C₂₈H₃₈O₇        486.60