Printed on: Mon Apr 03 2023, 05:38:26 AM(EST) Status: Currently Official on 03-Apr-2023 DocId: GUID-5B365E21-6343-40BC-9ED4-430313F805FC_4_en-US

Printed by: Elizabete Bete Official Date: Official as of 01-May-2020 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: gal6i DOI: https://doi.org/10.31003/USPNF_M18334_04_01
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[NOTE—The relative retention times for clobetasol

Clobetasol Propionate propionate and beclomethasone dipropionate are
1.0 and 1.6, respectively.]
Calculate the percentage of C25H32ClFO5 in the portion of
Clobetasol Propionate taken:

Result = (RU/RS) × (CS/CU) × 100

RU = ratio of the clobetasol propionate peak area to the

C25H32ClFO5 466.97 internal standard peak area from the Sample
Pregna-1,4-diene-3,20-dione, 21-chloro-9-fluoro-11- solution
hydroxy-16-methyl-17-(1-oxopropoxy)-, (11β,16β)-; RS = ratio of the clobetasol propionate peak area to the
21-Chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna- internal standard peak area from the Standard
1,4-diene-3,20-dione 17-propionate CAS RN®: 25122-46- solution
7; 25122-41-2; UNII: ADN79D536H. CS = concentration of USP Clobetasol Propionate RS
in the Standard solution (mg/mL)
DEFINITION CU = nominal concentration of clobetasol propionate
Clobetasol Propionate contains NLT 97.0% and NMT 102.0% in the Sample solution (mg/mL)
of C25H32ClFO5, calculated on the dried basis.
Acceptance criteria: 97.0%–102.0% on the dried basis
IDENTIFICATION
IMPURITIES
Change to read: INORGANIC IMPURITIES

al
• Residue on Ignition á281ñ: NMT 0.1%, using a platinum
▲
• SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared crucible
Spectroscopy: 197M▲ (CN 1-May-2020) ORGANIC IMPURITIES
ASSAY • Procedure
• PROCEDURE
ci Solution A, Mobile phase, System suitability solution, and
Solution A: 0.05 M monobasic sodium phosphate. Adjust Chromatographic system: Proceed as directed in the
with 85% phosphoric acid to a pH of 2.5. Assay.
Mobile phase: Acetonitrile, methanol, and Solution A Sample solution: 0.1 mg/mL of Clobetasol Propionate in
(19:4:17) Mobile phase
Internal standard solution: 0.2 mg/mL of beclomethasone Analysis
Sample: Sample solution
ffi
dipropionate in methanol
Standard solution: Dissolve a quantity of USP Clobetasol Calculate the percentage of each impurity in the portion of
Propionate RS in methanol and Internal standard solution to Clobetasol Propionate taken:
obtain a final solution of 0.04 mg/mL of USP Clobetasol
Propionate RS and 0.08 mg/mL of beclomethasone Result = (rU/rT) × 100
dipropionate.
rU = peak area for each impurity
O

System suitability solution: 0.001 mg/mL of USP

Clobetasol Propionate Related Compound A RS and rT = sum of the areas of all of the peaks
0.1 mg/mL of USP Clobetasol Propionate RS in Mobile phase
Sample solution: Transfer 4 mg of Clobetasol Propionate Acceptance criteria
to a 100-mL volumetric flask, add 40.0 mL of Internal Any individual impurity: NMT 1.0%
standard solution, and dilute with methanol to volume. Total impurities: NMT 2.5%
Chromatographic system SPECIFIC TESTS
(See Chromatography á621ñ, System Suitability.) • MELTING RANGE OR TEMPERATURE á741ñ: Approximately
Mode: LC 196°
Detector: UV 240 nm • OPTICAL ROTATION, Specific Rotation á781Sñ: +98° to +104°
Column: 4.6-mm × 15-cm; packing L1 at 20°
Flow rate: 1 mL/min Sample solution: 10 mg/mL in dioxane
Injection size: 10 µL • LOSS ON DRYING á731ñ: Dry a sample at 105° for 3 h: it loses
System suitability NMT 2.0% of its weight.
Sample: System suitability solution
[NOTE—The relative retention times for clobetasol ADDITIONAL REQUIREMENTS
propionate and clobetasol propionate related • PACKAGING AND STORAGE: Preserve in tight, light-resistant
compound A are 1.0 and 1.1, respectively.] containers.
Suitability requirements • USP REFERENCE STANDARDS á11ñ
Resolution: NLT 1.5 between clobetasol propionate and USP Clobetasol Propionate RS
clobetasol propionate related compound A USP Clobetasol Propionate Related Compound A RS
Column efficiency: NLT 5000 theoretical plates for the 9α-Fluoro-11β-hydroxy-16β-methyl 3-oxo-androsta-1,4-
clobetasol propionate peak diene-17(R)-spiro-2′-[4′-chloro-5′-ethylfuran-3′(2′H)-
Tailing factor: NMT 2.0 for the clobetasol one].
propionate peak C25H30ClFO4 448.96
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution

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