Fluocinolone Acetonide

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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C₂₄H₃₀F₂O₆ (anhydrous) 452.49

Dihydrate 488.53

Pregna-1,4-diene-3,20-dione, 6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, (6α,11β,16α)-;

6α,9-Difluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione, cyclic 16,17-acetal with acetone CAS RN^®: 67-73-2; UNII: 0CD5FD6S2M.

1 DEFINITION

Fluocinolone Acetonide is anhydrous or contains two molecules of water of hydration. It contains NLT 97.0% and NMT 102.0% of fluocinolone acetonide (C₂₄H₃₀F₂O₆), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K: If a difference appears, dissolve portions of both the sample and the USP Reference Standard in ethyl acetate, evaporate to dryness, and repeat the test on the residues.

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: Acetonitrile, tetrahydrofuran, and water (13:10:77)

Diluent: Acetonitrile and tetrahydrofuran (13:10)

Standard solution: 0.2 mg/mL of USP Fluocinolone Acetonide RS, prepared as follows. Transfer a suitable amount of USP Fluocinolone Acetonide RS to a suitable volumetric flask, and dissolve in a volume of Diluent equal to 23% of the flask volume. Dilute with water to volume.

Sample solution: 0.2 mg/mL of Fluocinolone Acetonide, prepared as follows. Transfer a suitable amount of Fluocinolone Acetonide to a suitable volumetric flask, and dissolve in a volume of Diluent equal to 23% of the flask volume. Dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 10-cm; 5-µm packing L1

Flow rate: 2.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluocinolone acetonide (C₂₄H₃₀F₂O₆) in the portion of Fluocinolone Acetonide taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%-102.0% on the dried basis

Change to read:

3.2 ORGANIC IMPURITIES

Protect the solutions from light throughout the test.

Mobile phase: Acetonitrile and water (45:55), prepared as follows. Mix 450 mL of acetonitrile and 500 mL of water, and allow to equilibrate. Add water to make 1000 mL.

System suitability solution: 0.25 mg/mL each of USP Fluocinolone Acetonide RS and USP Triamcinolone Acetonide RS, prepared as follows. Transfer suitable amounts of USP Fluocinolone Acetonide RS and USP Triamcinolone Acetonide RS to a suitable volumetric flask. Dissolve in 45% of the flask volume of acetonitrile, and dilute with water to volume.

Standard solution: 0.025 mg/mL of USP Fluocinolone Acetonide RS in acetonitrile

Sample solution: 2.5 mg/mL of Fluocinolone Acetonide in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 238 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: 4 times the retention time of fluocinolone acetonide

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for triamcinolone acetonide and fluocinolone acetonide are 0.85 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between triamcinolone acetonide and fluocinolone acetonide, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Fluocinolone Acetonide taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of fluocinolone acetonide from the Standard solution

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

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

Acceptance criteria

Any individual impurity: NMT 1%; NMT one such peak is greater than 0.5%.

Total impurities: NMT 2.5%. Disregard any peak below 0.05% of the peak area of fluocinolone acetonide from the Sample solution (ERR 1-Jun-2022).

4 SPECIFIC TESTS

4.1 OPTICAL ROTATION, Specific Rotation(781S)

Sample solution: 10 mg/mL in methanol

Acceptance criteria: +98° to +108°

4.2 LOSS ON DRYING (731)

Analysis: Dry under vacuum at 105° for 3 h.

Acceptance criteria: NMT 1.0% for anhydrous Fluocinolone Acetonide; NMT 8.5% for hydrous Fluocinolone Acetonide

5 ADDITIONAL REQUIREMENTS

5.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

5.2 LABELING

Label it to indicate whether it is anhydrous or hydrous.

5.3 USP REFERENCE STANDARDS (11)

USP Fluocinolone Acetonide RS

USP Triamcinolone Acetonide RS