Fluticasone Propionate

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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C₂₅H₃₁F₃O₅S 500.57

Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)-, (6α,11β,16α,17α)-S-(fluoromethyl) ester, S-Fluoromethyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate;

6α,9-Difluoro-17-{[(fluoromethyl)sulfanyl] carbonyl}-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl propanoate (USP 1-Dec-2022) CAS RN^®: 80474-14-2; UNII: O2GMZ0LF5W.

Change to read:

1 DEFINITION

Fluticasone Propionate contains NLT 98.0% and NMT102.0% (USP 1-Dec-2022) of fluticasone propionate (USP 1-Dec-2022) (C₂₅H₃₁F₃O₅S), calculated on the anhydrous, solvent-free basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A, 197K (USP 1-Dec-2022), or 197M

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

Buffer: 1.15 g/L of monobasic ammonium phosphate, adjusted with phosphoric acid to a pH of 3.5 (USP 1-Dec-2022)

Mobile phase: Methanol, acetonitrile, and Buffer (50:15:35)

System suitability solution: 0.04 mg/mL of USP Fluticasone Propionate RS and 0.008 mg/mL of USP Fluticasone Propionate Related Compound D RSA (USP 1-Dec-2022) 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

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

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 volume: 20 µL

3.3 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 0.73%, (USP 1-Dec-2022) Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluticasone propionate (C₂₅H₃₁F₃O₅S) in the portion of Fluticasone Propionate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of fluticasone propionate from the Sample solution

r_S = peak response of fluticasone propionate from the Standard solution

C_S = concentration of USP Fluticasone Propionate RS in the Standard solution (mg/mL)

C_U = concentration of Fluticasone Propionate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%- 102.0% (USP 1-Dec-2022) on the anhydrous, solvent-free basis

4 IMPURITIES

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4.1 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: 0.2 mg/mL of USP Fluticasone Propionate System Suitability Mixture RS prepared as follows. Transfer a suitable amount of USP Fluticasone Propionate System Suitability Mixture RS to an appropriate volumetric flask and dissolve in 50% of the flask volume of Solution A. Sonication may be used to aid dissolution. Dilute with Solution C to volume.

Sensitivity stock solution: 0.1 mg/mL of USP Fluticasone Propionate RS prepared as follows. Transfer a suitable amount of USP Fluticasone Propionate RS to an appropriate volumetric flask and dissolve in 50% of the flask volume of Solution A. Sonication may be used to aid dissolution. Dilute with Solution C to volume.

Sensitivity solution: 0.1 µg/mL of USP Fluticasone Propionate RS from Sensitivity stock solution in Solution CA (USP 1-Dec-2022)

Sample solution: 0.2 mg/mL of Fluticasone Propionate (USP 1-Dec-2022) prepared as follows. Transfer a suitable amount of Fluticasone Propionate to an appropriate volumetric flask and dissolve in 50% of the flask volume of Solution A. Sonication may be used to aid dissolution. Dilute with Solution C to volume. (USP 1-Dec-2022)

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 239 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Sensitivity solution (USP 1-Dec-2022)

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, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Dec-2022)

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Fluticasone Propionate taken:

Result = (r_U/r_T) x 100

r_U = peak response for each impurity

r_T = sum of the responses of all the peaks

Acceptance criteria: See Table 2. The reporting threshold is 0.05% (USP 1-Dec-2022)

Table 2

^a 6α,9-Difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbonylsulfenic acid.

^b 6α,9-Difluoro-17-{[(fluoromethyl)sulfanyl]carbonyl}-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl 64,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylate.

Change to read:

4.2 LIMIT OF ACETONE

Internal standard solution: 0.05% (v/v) solution of tetrahydrofuran in dimethylformamide

Standard solution: 0.05% (v/v) acetone in Internal standard solution

Sample solution: 50 mg/mL of Fluticasone Propionate in the Internal standard solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 25-m; 2-µm film of phase G16

Carrier gas: Nitrogen or helium

Temperatures

Detector: 250°

Splitless injector: 150°

Column: See Table 3.

Table 3

Flow rate: 5.5 mL/min

Injection volume: 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 (USP 1-Dec-2022) in the portion of Fluticasone Propionate taken:

Result = (R_U/R_S) x D x (C_S/C_U)

R_U = peak response ratio of acetone to tetrahydrofuran from the Sample solution

R_S = peak response ratio of acetone to tetrahydrofuran from the Standard solution

D = density of acetone at 20° (g/mL)

C_S = concentration of acetone in the Standard solution (% v/v)

C_U = concentration of Fluticasone Propionate in the Sample solution (g/mL)

Acceptance criteria: NMT 1.0% (USP 1-Dec-2022)

5 SPECIFIC TESTS

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5.1 OPTICAL ROTATION (781S), Procedures, Specific Rotation:

Sample solution: 0.5 g/100 mL (USP 1-Dec-2022) of Fluticasone Propionate in dichloromethane (USP 1-Dec-2022)

Acceptance criteria: +32° to +36° at 20°, calculated on the anhydrous, solvent-free basis

Change to read:

5.2 WATER DETERMINATION (921), Method I

NMT 0.2% (USP 1-Dec-2022)

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight, light-resistant containers, and store at a temperature not exceeding 30°.

Delete the following:

LABELING (USP 1-Dec-2022)

Change to read:

6.2 USP REFERENCE STANDARDS (11)

USP Fluticasone Propionate RS

USP Fluticasone Propionate Related Compound D RS

6α,9-Difluoro-11β-hydroxy-16α-methyl-17-[(methylsulfanyl) carbonyl]-3-oxoandrosta-1,4-dien-17α-yl propanoate;

Also known as S-methyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate.

C₂₅H₃₂F₂O₅S 482.58 (USP 1-Dec-2022)

USP Fluticasone Propionate System Suitability Mixture RS

Contains a mixture of the following 4 compounds:

Fluticasone propionate.

Fluticasone propionate related compound B: 6α,9-Difluoro-11β-hydroxy-16α-methyl-2',3,4'-trioxo-17α-spiro [androsta-1,4-diene-17,5'-(1,3)oxathiolane].

C₂₂H₂₄F₂O₅S 438.49

Fluticasone propionate related compound C: 6α, 9-Difluoro-17-{[(fluoromethyl) sulfanyl]carbonyl}-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl acetate;

Also known as S-Fluoromethyl 17α-acetyloxy-6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate.

C₂₄H₂₉F₃O₅S 486.55

Fluticasone propionate related compound D. (USP 1-Dec-2022)