Fluorouracil Cream

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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1 DEFINITION

Fluorouracil Cream contains NLT 90.0% and NMT 110.0% of the labeled amount of fluorouracil (C₄H₃FN₂O₂). It may contain Sodium Hydroxide to adjust the pH.

2 IDENTIFICATION

Change to read:

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

Sample: Dry a portion of Cream nominally equivalent to 50 mg of fluorouracil at a pressure NMT 0.7 kPa. Mix with 100 mL of ether. Decant, wash the residue with 50 mL of ether, and allow to air dry.

Acceptance criteria: Meets the requirements

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

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with 5 M potassium hydroxide to a pH of 5.7 ± 0.1.

Mobile phase: Acetonitrile and Buffer (5:95)

Standard solution: 10 μg/mL of USP Fluorouracil RS in water

Sample stock solution: Nominally equivalent to 0.1 mg/mL of fluorouracil prepared as follows. Transfer a portion of Cream, nominally equivalent to 10 mg of fluorouracil, into a 100-mL volumetric flask. Add 20 mL of methanol, and mix on a vortex mixer to dissolve. Dilute with water to volume.

Sample solution: 10 μg/mL of fluorouracil in water, from Sample stock solution. Mix, and filter.

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: 1.0 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Relative standard deviation: NMT 0.73%, Standard solution

Tailing factor: NMT 1.5, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluorouracil (C₄H₃FN₂O₂) in the portion of Cream taken:

Result = (r_U/r_S) × (C_S/C_U)× 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Limit of Urea

Standard solution: 0.05 mg/mL of USP Urea RS in water

Sample solution: Nominally equivalent to 5 mg/mL of fluorouracil prepared as follows. Shake a portion of Cream containing 100 mg of fluorouracil with 10 mL of water for 5 min. Add 10 mL of alcohol, and mix. Pass through a glass-ber filter, and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: Chromatographic silica gel

Application volume: 20 μL

Developing solvent system: Ethyl acetate, acetone, and water (70:40:10)

Reagent solution: Prepare a 10-mg/mL solution of p-dimethylaminobenzaldehyde in alcohol. Prepare a mixture of this solution and hydrochloric acid (10:1).

Analysis

Samples: Standard solution and Sample solution

Procedure: Develop with Developing solvent system, followed by air drying. Spray the plate at least twice with Reagent solution, and dry the plate in an oven at 100° until the maximum intensity of the spots is obtained. Examine the plate under daylight.

Acceptance criteria: NMT 1.0%; the spot of urea in the Sample solution is not more intense than the spot of urea from the Standard solution.

5 PERFORMANCE TESTS

Minimum Fill 〈755〉: Meets the requirements

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fluorouracil RS

USP Urea RS

Urea.

CH₄N₂O 60.06