Flucytosine Capsules

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

Flflucytosine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of flucytosine (C₄H₄FN₃O).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet Absorption: 197U

Wavelength range: 260–350 nm

Diluent: 0.1 N hydrochloric acid

Standard solution: 8 µg/mL of USP Flucytosine RS in Diluent

Sample stock solution: Nominally 1 mg/mL of flucytosine in Diluent prepared as follows. Remove the contents of Capsules (NLT 20) as completely as possible, and weigh. Transfer a portion of the powder, nominally equivalent to 250 mg of flucytosine, to a 250-mL volumetric ask. Add 50 mL of Diluent, shake by mechanical means for 30 min and dilute with Diluent to volume. Pass the solution through a suitable membrane filter of 0.45-µm pore size.

Sample solution: Nominally 8 µg/mL of flucytosine in Diluent from Sample stock solution

Blank: Diluent

Acceptance criteria: Meet the requirements _{(USP 1-May-2022)}

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B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _{(USP 1-May-2022)}

3 ASSAY

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Procedure

Buffer: 13.6 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.0.

Solution A: Buffer and methanol (98:2)

Solution B: Buffer and methanol (85:15)

Mobile phase: See Table 1.

Table 1

Diluent: Dissolve 13.6 g of monobasic potassium phosphate in 980 mL of water. Add 20 mL of methanol and mix. Standard solution: 0.05 mg/mL of USP Flucytosine RS in Diluent

Sample solution: Nominally 0.05 mg/mL of flucytosine in Diluent prepared as follows. Remove the contents of Capsules (NLT 10) as completely as possible, and weigh. Transfer a portion of the powder, nominally equivalent to 10 mg of flucytosine, to a 200-mL volumetric ask. Add 100 mL of Diluent and shake for 30 min. Dilute with Diluent to volume and mix. Pass a portion of the solution under test through a suitable filter.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 284 nm

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

Flow rate: 1.1 mL/min

Injection volume: 20 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of flucytosine (C₄H₄FN₃O) in the portion of Capsules taken:

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

r_U = peak response of flucytosine from the Sample solution

r_S = peak response of flucytosine from the Standard solution

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

C_U = nominal concentration of flucytosine in the Sample solution (mg/mL) (USP 1-May-2022)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

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Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 75 rpm

Time: 60 min

(USP 1-May-2022)

Standard solution: USP Flucytosine RS in Medium

Sample solution: Dilute with Medium to a concentration that is similar to that of the Standard solution. Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 276 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of flucytosine (C₄H₄FN₃O) dissolved:

Result = (A_U /A_S ) × C_S × D × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

L = label claim (mg/Capsule) (USP 1-May-2022)

Tolerances: NLT 80% (Q) of the labeled amount of flucytosine (C₄H₄FN₃O) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

Add the following:

5 IMPURITIES

Organic Impurities

Buffer, Solution A, Solution B, Mobile phase, and Diluent: Prepare as directed in the Assay.

Sensitivity solution: 0.00015 mg/mL of USP Flucytosine RS in Diluent

Standard solution: 0.00030 mg/mL of USP Flucytosine RS and 0.00045 mg/mL of USP Fluorouracil RS in Diluent

Sample solution: Nominally 0.3 mg/mL of flucytosine in Diluent prepared as follows. Remove the contents of Capsules (NLT 10) as completely as possible, and weigh. Transfer a portion of the powder, nominally equivalent to 15 mg of flucytosine, to a 50-mL volumetric ask. Add 25 mL of Diluent and shake for 30 min. Dilute with Diluent to volume and mix. Pass a portion of the solution under test through a suitable filter.

5.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

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

Flow rate: 1.1 mL/min

Injection volume: 20 µL

5.2 System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0% each for flucytosine and fluorouracil, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluorouracil in the portion of Capsules taken:

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

r_U = peak response of fluorouracil from the Sample solution

r_S = peak response of fluorouracil from the Standard solution

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

C = nominal concentration of flucytosine in the Sample solution (mg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Capsules taken:

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

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of flucytosine from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature. _{(USP 1-May-2022)}

Change to read:

USP Reference Standards 〈11〉

USP Flucytosine RS

USP Fluorouracil RS (USP 1-May-2022)