Clocortolone Pivalate

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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C₂₇H₃₆ClFO₅ 495.03

Pregna-1,4-diene-3,20-dione, 9-chloro-21-(2,2-dimethyl-1-oxopropoxy)-6-fluoro-11-hydroxy-16-methyl-, (6α,11β,16α)-;

9-Chloro-6α-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione 21-pivalate

CAS RN®: 34097-16-0; UNII: QBL8IZH14X.

1 DEFINITION 

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Clocortolone Pivalate contains NLT 98.0% and NMT 102.0% of clocortolone pivalate (C₂₇H₃₆ClFO₅), calculated on the dried basis.

2 IDENTIFICATION

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A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M or 197A

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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

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3.1 Procedure

3.1.1 Mobile phase: Acetonitrile and water (60:40)

Standard solution: 1 mg/mL of USP Clocortolone Pivalate RS in acetonitrile

Sample solution: 1 mg/mL of Clocortolone Pivalate in acetonitrile

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 240 nm
• Column: 4.0-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1 mL/min
• Injection volume: 10 µL
• Run time: NLT 2 times the retention time of clocortolone pivalate

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 1.5
• Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clocortolone pivalate (C₂₇H₃₆ClFO₅) in the portion of Clocortolone Pivalate taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clocortolone pivalate from the Sample solution

r_s = peak response of clocortolone pivalate from the Standard solution

C_s = concentration of USP Clocortolone Pivalate RS in the Standard solution (mg/mL)

C_u = concentration of Clocortolone Pivalate in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

Sample: 100 mg

Acceptance criteria: NMT 0.2%

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4.2 Organic Impurities

4.2.1 Mobile phase: Prepare as directed in the Assay.

System suitability solution: 0.5 mg/mL each of USP Clocortolone RS and USP Clocortolone Pivalate RS in acetonitrile

Sensitivity solution: 0.00125 mg/mL of USP Clocortolone Pivalate RS in acetonitrile

Standard solution: 0.0125 mg/mL of USP Clocortolone Pivalate RS in acetonitrile

Sample solution: 2.5 mg/mL of Clocortolone Pivalate in acetonitrile

Chromatographic system: Proceed as directed in the Assay except for the following.

• Injection volume: 20 µL
• Run time: NLT 3.3 times the retention time of clocortolone pivalate

System suitability

• Samples: System suitability solution, Sensitivity solution, and Standard solution
• Suitability requirements
• Resolution: NLT 1.5 between clocortolone and clocortolone pivalate, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clocortolone or any unspecified impurity in the portion of Clocortolone Pivalate taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clocortolone or any unspecified impurity from the Sample solution

r_s = peak response of clocortolone pivalate from the Standard solution

C_s = concentration of USP Clocortolone Pivalate RS in the Standard solution (mg/mL)

C_u = concentration of Clocortolone Pivalate in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

5 SPECIFIC TESTS

5.1 Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 40 mg/mL, in chloroform

Acceptance criteria: +125° to +135°

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

5.3 Delete the following

Color and Clarity of Solution:

• Sample solution: 1-in-100 solution of clocortolone pivalate in chloroform
• Acceptance criteria: Solution is clear and practically colorless.

6 ADDITIONAL REQUIREMENTS

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

Change to read:

• USP Reference Standards 〈11〉
• USP Clocortolone RS
• USP Clocortolone Pivalate RS