Clobetasol Propionate
(kloe bay' ta sol proe' pee oh nate).
Click to View Image

C25H32ClFO5 466.97
Pregna-1,4-diene-3,20-dione, 21-chloro-9-fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-, (11,16)-;    
21-Chloro-9-fluoro-11,17-dihydroxy-16-methylpregna-1,4-diene-3,20-dione 17-propionate     [25122-46-7; 25122-41-2].
DEFINITION
Clobetasol Propionate contains NLT 97.0% and NMT 102.0% of C25H32ClFO5, calculated on the dried basis.
IDENTIFICATION
ASSAY
•  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 
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 peak
Tailing factor:  NMT 2.0 for the clobetasol 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 = (RU/RS) × (CS/CU) × 100
RU== ratio of the clobetasol propionate peak area to the internal standard peak area from the Sample solution
RS== ratio of the clobetasol propionate peak area to the internal standard peak area from the Standard solution
CS== concentration of USP Clobetasol Propionate RS in the Standard solution (mg/mL)
CU== nominal concentration of clobetasol propionate in the Sample solution (mg/mL)
Acceptance criteria:  97.0%–102.0% on the dried basis
IMPURITIES
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%, using a platinum crucible
•  Heavy Metals, Method II 231: NMT 20 ppm
Organic Impurities 
•  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 = (rU/rT) × 100
rU== peak area for each impurity
rT== sum of the areas of all of the peaks
Acceptance criteria 
Any individual impurity:  NMT 1.0%
Total impurities:  NMT 2.5%
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.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers.
•  USP Reference Standards 11
USP Clobetasol Propionate RS Click to View Structure
USP Clobetasol Propionate Related Compound A RS Click to View Structure
9-Fluoro-11-hydroxy-16-methyl 3-oxo-androsta-1,4-diene-17(R)-spiro-2¢-[4¢-chloro-5¢-ethylfuran-3¢(2¢H)-one].
    C25H30ClFO4         448.96
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Domenick Vicchio, Ph.D.
Senior Scientific Liaison
1-301-998-6828
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2713
Pharmacopeial Forum: Volume No. 35(5) Page 1125