Fluorometholone

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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C₂₂H₂₉FO₄376.46

Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17-dihydroxy-6-methyl-, (6α,11β)-;

9-Fluoro-11β,17-dihydroxy-6α-methylpregna-1,4-diene-3,20-dione CAS RN®: 426-13-1; UNII: SV0CSG527L.

1 DEFINITION

Fluorometholone contains NLT 97.0% and NMT 103.0% of fluorometholone (C₂₂H₂₉FO₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

3.1 Procedure

Mobile phase: Mix 425 g (538 mL) of methanol and 400 g (400 mL) of water. Adjust with phosphoric acid to a pH of 2.4.

Standard stock solution: 0.25 mg/mL of USP Fluorometholone RS prepared as follows. Transfer a suitable amount of USP Fluorometholone RS to a suitable volumetric flask and dissolve in 2% of the final volume of tetrahydrofuran. Dilute with Mobile phase to volume.

Standard solution: 50 μg/mL of USP Fluorometholone RS in Mobile phase from Standard stock solution

Sample stock solution: 0.25 mg/mL of Fluorometholone prepared as follows. Transfer a suitable amount of Fluorometholone to a suitable volumetric flask and dissolve in 2% of the final volume of tetrahydrofuran. Dilute with Mobile phase to volume.

Sample solution: 50 μg/mL of Fluorometholone in Mobile phase from Sample stock solution

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Flow rate: 0.6 mL/min

Injection volume: 20 μL

Run time: NLT 1.6 times the retention time of fluorometholone

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 1.3

Relative standard deviation: NMT 0.73%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluorometholone (C₂₂H₂₉FO₄) in the portion of Fluorometholone taken:

Result =( r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of fluorometholone from the Sample solution

r_S = peak response of fluorometholone from the Standard solution

C_S = concentration of USP Fluorometholone RS in the Standard solution (μg/mL)

C_U = concentration of Fluorometholone in the Sample solution (μg/mL)

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

4.1 Organic Impurities

Mobile phase: Proceed as directed in the Assay.

System suitability stock solution: 0.5 mg/mL each of USP Fluorometholone RS and USP Fluorometholone Related Compound A RS prepared as follows. Transfer a suitable amount of USP Fluorometholone RS and USP Fluorometholone Related Compound A RS to a suitable volumetric flask and dissolve in 4% of the final volume of tetrahydrofuran. Dilute with Mobile phase to volume.

System suitability solution: 0.005 mg/mL each of USP Fluorometholone RS and USP Fluorometholone Related Compound A RS in Mobile phase from System suitability stock solution

Standard stock solution: 0.5 mg/mL of USP Fluorometholone RS prepared as follows. Transfer a suitable amount of USP Fluorometholone RS to a suitable volumetric flask and dissolve in 4% of the final volume of tetrahydrofuran. Dilute with Mobile phase to volume.

Standard solution: 0.5 μg/mL of USP Fluorometholone RS in Mobile phase from Standard stock solution

Sample solution: 0.5 mg/mL of Fluorometholone prepared as follows. Transfer a suitable amount of Fluorometholone to a suitable volumetric flask and dissolve in 4% of the final volume of tetrahydrofuran. Dilute with Mobile phase to volume.

Chromatographic system: Proceed as directed in the Assay except for the Run time.

Run time: NLT 2.1 times the retention time of fluorometholone

4.2 System suitability

Samples: System suitability solution and Standard solution

4.3 Suitability requirements

Resolution: NLT 3 between fluorometholone and fluorometholone related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Fluorometholone taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of fluorometholone from the Standard solution

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

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

Acceptance criteria: See Table 1. Disregard any peaks below 0.02%.

Table 1

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL in dimethyl sulfoxide

Acceptance criteria: +62° to +70°

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 60° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Fluorometholone RS

USP Fluorometholone Related Compound A RS

11β,17α-Dihydroxy-6α-methylpregna-1,4-diene-3,20-dione.

C₂₂H₃₀O₄ 358.47