Flutamide

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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C₁₁H₁₁F₃N₂O₃              276.21

Propanamide, 2-methyl-N-[4-nitro-3-trifluoromethyl)phenyl]-;

α,α,α-Trifluoro-2-methyl-4′-nitro-m-propionotoluidide CAS RN®: 13311-84-7; UNII: 76W6J0943E.

1 DEFINITION

Flutamide contains NLT 98.0% and NMT 101.0% of flutamide (C₁₁H₁₁F₃N₂O₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. The retention time of the major peak from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (45:55)

Diluent: Acetonitrile and water (20:80)

System suitability stock solution: 1 mg/mL of USP o-Flutamide RS, prepared as follows. Dissolve the Standard in acetonitrile using 20% of the nal volume. Sonicate to dissolve. Dilute with water to volume. Mix, and allow to warm to room temperature.

Standard solution: 0.2 mg/mL of USP Flutamide RS, prepared as follows. Dissolve the Standard in acetonitrile using 20% of the nal volume. Sonicate to dissolve. Dilute with water to volume. Mix, and allow to warm to room temperature.

System suitability solution: 10 µg/mL each of USP o-Flutamide RS and USP Flutamide RS in Diluent prepared from the System suitability stock solution and the Standard solution

Sample solution: 0.2 mg/mL of Flutamide, prepared as follows. Dissolve a previously dried sample in acetonitrile using 20% of the nal volume. Sonicate to dissolve. Dilute with water to volume. Mix, and allow to warm to room temperature.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Column temperature: 25 ± 5°

Flow rate: 1 mL/min

Injection volume: 20 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—For the relative retention times, see Table 1.]

Suitability requirements

Resolution: NLT 6.0 between utamide and o-utamide, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.5%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of utamide (C₁₁H₁₁F₃N₂O₃) in the portion of Flutamide taken:

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

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

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

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

Acceptance criteria: 98.0%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Mobile phase, Diluent, Standard solution, Sample solution, and Chromatographic system: Prepare as directed in the Assay.

System suitability stock solution: 1 mg/mL each of USP o-Flutamide RS, USP Flutamide Related Compound A RS, and USP Flutamide Related Compound B RS, prepared as follows. Dissolve the Standards in acetonitrile using 20% of the nal volume. Sonicate to dissolve. Dilute with water to volume. Mix, and allow to warm to room temperature.

System suitability solution: 10 µg/mL each of USP o-Flutamide RS, USP Flutamide Related Compound A RS, USP Flutamide Related Compound B RS, and USP Flutamide RS in Diluent, prepared from the System suitability stock solution and Standard solution

Sensitivity solution: 0.1 µg/mL of USP Flutamide RS from the Standard solution in Diluent

4.1 System suitability

Samples: System suitability solution and Sensitivity solution

[Note—For the relative retention times, see Table 1.]

Suitability requirements

Resolution: NLT 6.0 between utamide and o-utamide; NLT 2.0 between utamide related compound A and utamide related compound B, System suitability solution

Relative standard deviation: NMT 10.0% for utamide, Sensitivity solution

4.2 Analysis

Sample: Sample solution

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

Result = (r_U /r_T ) × (1/F) × 100

r_U = peak area for each impurity

r_T = sum of all the peak responses

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a N-[4-Nitro-3-(triuoromethyl)phenyl]acetamide.

^b 4-Nitro-3-(triuoromethyl)aniline.

^c N-[4-Nitro-3-(triuoromethyl) phenyl]propionamide.

^d N-[3-(Triuoromethyl)phenyl]isobutyramide.

^e N-[2-Nitro-3-(triuoromethyl)phenyl]isobutyramide.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry a sample in vacuum at 60° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Flutamide RS

USP o-Flutamide RS

N-[2-Nitro-3-(trifluoromethyl)phenyl]isobutyramide.

C₁₁H₁₁F₃N₂O₃               276.21

USP Flutamide Related Compound A RS

4-Nitro-3-(trifluoromethyl)aniline.

C₇H₅F₃N₂O₂                206.12

USP Flutamide Related Compound B RS

N-[4-Nitro-3-(trifluoromethyl)phenyl]acetamide.

C₉H₇F₃N₂O₃              248.16