Fluticasone Propionate
(floo tik' a sone proe' pee oh nate).
C25H31F3O5S 500.57 Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)-, (6,11,16,17)-S-(fluoromethyl) ester; S-Fluoromethyl 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxyandrosta-1,4-diene-17-carbothioate [80474-14-2]. DEFINITION
Fluticasone Propionate contains NLT 98.0% and NMT 101.0% of C25H31F3O5S, calculated on the anhydrous, solvent-free basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
1.15 g/L of monobasic ammonium phosphate, adjusted with phosphoric acid to a pH of 3.5 ± 0.05
Mobile phase:
Methanol, acetonitrile, and Buffer (50:15:35)
System suitability solution:
0.05 mg/mL of USP Fluticasone Propionate Resolution Mixture RS in Mobile phase
Standard solution:
0.04 mg/mL of USP Fluticasone Propionate RS in Mobile phase
Sample solution:
0.04 mg/mL of Fluticasone Propionate in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 239 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[NoteThe relative retention times for fluticasone propionate and fluticasone propionate related compound D are about 1.0 and 1.10, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between fluticasone propionate and fluticasone propionate related compound D, System suitability solution
Relative standard deviation:
NMT 2%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of fluticasone propionate (C25H31F3O5S) in the portion of Fluticasone Propionate taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%101.0% on the anhydrous, solvent-free basis
IMPURITIES
• Organic Impurities
Solution A:
0.5 mL of phosphoric acid in 1000 mL of acetonitrile
Solution B:
0.5 mL of phosphoric acid in 1000 mL of methanol
Solution C:
0.5 mL of phosphoric acid in 1000 mL of water
Mobile phase:
See Table 1.
Table 1
System suitability solution:
Dissolve 2.0 mg of USP Fluticasone Propionate System Suitability Mixture RS in 5 mL of Solution A using sonication. Add 5 mL of Solution C.
Sample solution:
2.0 mg/mL prepared as follows: Dissolve 2.0 mg of Fluticasone Propionate in 5 mL of Solution A using sonication. Add 5 mL of Solution C.
Chromatographic system
Mode:
LC
Detector:
UV 239 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
System suitability solution
Suitability requirements
Resolution:
NLT 0.6 between fluticasone propionate related compound B and fluticasone propionate related compound C; NLT 1.5 between fluticasone propionate related compound D and fluticasone propionate
Analysis
Sample:
Sample solution
Calculate the percentage of each impurity in the portion of Fluticasone Propionate taken:
Result = (rU/rT) × 100
Acceptance criteria:
See Table 2.
Table 2
• Limit of Acetone
Internal standard solution:
0.05% (v/v) solution of tetrahydrofuran in dimethylformamide
Standard solution:
0.05% (v/v) of acetone in Internal standard solution
Sample solution:
50 mg/mL of Fluticasone Propionate in the Internal standard solution
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
0.53-mm × 25-m; 2-µm film of phase G16
Carrier gas:
Nitrogen or helium
Temperature
Detector:
250
Splitless injector:
150
Column:
See Table 3.
Table 3
Flow rate:
5.5 mL/min
Injection size:
0.1 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 5.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of acetone (w/w) in the portion of Fluticasone Propionate taken:
Result = (RU/RS) × D × (CS/CU)
Acceptance criteria:
NMT 1.0% (w/w)
SPECIFIC TESTS
• Optical Rotation, Specific Rotation 781S:
+32 to +36 at 20, calculated on the anhydrous, solvent-free basis
Sample solution:
0.5% (w/v) of Fluticasone Propionate in dichloromethane (0.5 g in 100 mL)
• Water Determination, Method I 921:
NMT 0.2% (w/w)
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at a temperature not exceeding 30.
• Labeling:
Fluticasone Propionate in the form of microcrystals is so labeled.
• USP Reference Standards 11
USP Fluticasone Propionate Resolution Mixture RS
USP Fluticasone Propionate System Suitability Mixture RS
It is a mixture of USP Fluticasone Propionate RS and fluticasone propionate related compounds B, C, and D. Fluticasone propionate related compound A: 6,9-Difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxyandrosta-1,4-diene-17-carbonylsulfenic acid. Fluticasone propionate related compound B: 6,9-Difluoro-11-hydroxy-16-methyl-2¢,3,4¢-trioxo-17-spiro(androsta-1,4-diene-17,5¢-(1,3)oxathiolane). Fluticasone propionate related compound C: S-Fluoromethyl 17-acetyloxy-6,9-difluoro-11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothioate. Fluticasone propionate related compound D: S-Methyl 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothioate. Fluticasone propionate related compound E: 6,9-Difluoro-11,17-dihydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carboxylic acid 6,9-difluoro-17-(fluoromethylthio) carbonyl-11-hydroxy-16-methyl-3-oxo-androsta-1,4-dien-17-yl ester.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3261
Pharmacopeial Forum: Volume No. 32(2) Page 337
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