Fluticasone Propionate
(floo tik' a sone proe' pee oh nate).
Click to View Image

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
[Note—The 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
rU== peak response of fluticasone propionate from the Sample solution
rS== peak response of fluticasone propionate from the Standard solution
CS== concentration of USP Fluticasone Propionate RS in the Standard solution (mg/mL)
CU== concentration of Fluticasone Propionate in the Sample solution (mg/mL)
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
Time
(min)
Solution A
(%)
Solution B
(%)
Solution C
(%)
0 42 3 55
40 53 3 44
60 87 3 10
70 87 3 10
75 42 3 55
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
rU== peak response for each impurity
rT== sum of the responses of all the peaks
Acceptance criteria:  See Table 2.
Table 2
Name Relative
Retention
Time
Acceptance
Criteria,
NMT (%)
Fluticasone propionate related compound A 0.5 0.2
Fluticasone propionate related compound B 0.75 0.1
Fluticasone propionate related compound C 0.8 0.1
Fluticasone propionate related compound D 0.95 0.3
Fluticasone propionate 1.0
Fluticasone propionate related compound E 1.3 0.3
Any individual unspecified impurity 0.1
Total impurities* 1.0
*   Include all impurity peaks greater than or equal to 0.05%.
•  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
Initial
Temperature
()
Temperature
Ramp
(/min)
Final
Temperature
()
Hold Time at Final
Temperature
(min)
60 0 60 3.5
60 30 180 3.0
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)
RU== peak response ratio of acetone to tetrahydrofuran from the Sample solution
RS== peak response ratio of acetone to tetrahydrofuran from the Standard solution
D== density of acetone at 20 (g/mL)
CS== concentration of acetone in the Standard solution (%v/v)
CU== concentration of Fluticasone Propionate in the Sample solution (g/mL)
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 RS Click to View Structure
USP Fluticasone Propionate Resolution Mixture RS
USP Fluticasone Propionate System Suitability Mixture RS
It is a mixture of USP Fluticasone Propionate RS Click to View Structure 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.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
1-301-816-8330
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
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USP35–NF30 Page 3261
Pharmacopeial Forum: Volume No. 32(2) Page 337