Fluorometholone Acetate

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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C₂₄H₃₁FO₅ 418.51

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

9-Fluoro-11β,17-dihydroxy-6α-methylpregna-1,4-diene-3,20-dione, 17 acetate;

9-Fluoro-11β-hydroxy-6α-methyl-3,20-dioxopregna-1,4-dien-17-yl acetate. CAS RN®: 3801-06-7; UNII: 9I50C3I3OK.

Change to read:

1 DEFINITION

Fluorometholone Acetate contains NLT 98.0% and NMT 102.0% (USP 1-Dec-2021) of fluorometholone acetate (C₂₄H₃₁FO₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A (USP 1-Dec-2021)

Delete the following:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 10 μg/mL in methanol

Acceptance criteria: Meets the requirements (USP 1-Dec-2021)

Add the following:

B. The retention time of the fluorometholone acetate peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Dec-2021)

3 ASSAY

Change to read:

3.1 Procedure

Mobile phase: Acetonitrile and water (40:60)

System suitability stock solution: 1.0 mg/mL of USP Fluorometholone RS prepared as follows. Accurately weigh and transfer a portion of USP Fluorometholone RS to a suitable volumetric flask. Add methanol to 8% of the total volume and dilute with acetonitrile to volume. (USP 1-Dec-2021)

Standard solution: 1.0 mg/mL of USP Fluorometholone Acetate RS in acetonitrile

System suitability solution: 0.03 mg/mL each of USP Fluorometholone RS and USP Fluorometholone Acetate RS from System suitability stock solution and Standard solution, respectively, in acetonitrile

Sample solution: 1.0 mg/mL of Fluorometholone Acetate in acetonitrile

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.5 mL/min

Injection volume: 10 μL

Run time: NLT 2.5 times the retention time of the fluorometholone acetate peak (USP 1-Dec-2021)

3.3 System suitability

Samples: Standard solution and System suitability solution

[Note-See Table 1 for the relative retention times.] (USP 1-Dec-2021)

3.4 Suitability requirements

Resolution: NLT 10 between fluorometholone and fluorometholone acetate, System suitability solution (USP 1-Dec-2021)

Tailing factor: NMT 2.0 for fluorometholone acetate, Standard solution (USP 1-Dec-2021)

Relative standard deviation: NMT 0.73%, (USP 1-Dec-2021) Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluorometholone acetate (C₂₄H₃₁FO₅) in the portion of Fluorometholone Acetate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of fluorometholone acetate from the Sample solution

r_S = peak response of fluorometholone acetate from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% (USP 1-Dec-2021) on the dried basis

4 IMPURITIES

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4.1 Organic Impurities

Mobile phase and Sample solution: Prepare as directed in the Assay.

System suitability stock solution A: Prepare as directed for the System suitability stock solution in the Assay.

System suitability stock solution B: Prepare as directed for the Standard solution in the Assay.

System suitability solution: 0.03 mg/mL each of USP Fluorometholone RS and USP Fluorometholone Acetate RS, from System suitability stock solution A and System suitability stock solution B, respectively, in acetonitrile

Sensitivity solution: 0.5 μg/mL of USP Fluorometholone Acetate RS in acetonitrile (USP 1-Dec-2021)

Standard solution: 0.03 mg/mL of USP Fluorometholone RS from System suitability stock solution A in acetonitrile (USP 1-Dec-2021)

Chromatographic system: Proceed as directed in the Assay except for the Injection volume.

Injection volume: 20 μL

4.2 System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note-See Table 1 for the relative retention times.] (USP 1-Dec-2021)

4.3 Suitability requirements

Resolution: NLT 10 between fluorometholone and fluorometholone acetate, System suitability solution (USP 1-Dec-2021)

Relative standard deviation: NMT 5.0% based on peak height response, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Dec-2021)

4.4 Analysis

Samples: Standard solution and Sample solution (USP 1-Dec-2021)

Calculate the percentage of fluorometholone or fluorometholone diacetate in the portion of Fluorometholone Acetate taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak height response of fluorometholone or fluorometholone diacetate from the Sample solution

r_S = peak height 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 Acetate in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Calculate the percentage of all other fluorometholone acetate impurities in the portion of Fluorometholone Acetate taken:

Result = (r_U/r_T) × (1/F) × 100

r_U = peak area response of each impurity (except the fluorometholone and fluorometholone diacetate peaks) from the Sample solution

r_T = sum of the peak area responses of all impurity peaks plus the fluorometholone acetate peak from the Sample solution

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%. (USP 1-Dec-2021)

Table 1

^a Relative to fluorometholone. All other impurities relative to fluorometholone acetate unless otherwise marked. (USP 1-Dec-2021)

^b 9β,11β-Epoxy-17α-hydroxy-6α-methylpregna-1,4-diene-3,20-dione.

^c 9-Fluoro-6α-methyl-3,20-dioxopregna-1,4-dien-11β,17-diyl diacetate. (USP 1-Dec-2021)

^d 9β,11β-Epoxy-6α-methyl-3,20-dioxapregna-1,4-dien-17-yl acetate. (USP 1-Dec-2021)

^e 6α-Methyl-3,20-dioxopregna-1,4,7,9(11)-tetraen-17-yl acetate. (USP 1-Dec-2021)

^f 6α-Methyl-3,20-dioxopregna-1,4,9(11)-trien-17-yl acetate. (USP 1-Dec-2021)

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 20 mg/mL, in chloroform

Acceptance criteria: +25.0° to +31.0°

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 well-closed containers.

USP Reference Standards 〈11〉

USP Fluorometholone RS

USP Fluorometholone Acetate RS