Nilutamide

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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C₁₂H₁₀F₃N₃O₄         317.22

2,4-Imidazolidinedione, 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-;

5,5-Dimethyl-3-(α,a,a-trifluoro-4-nitro-m-tolyl)hydantoin;

5,5-Dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-imidazolidine-2,4-dione CAS RN^®: 63612-50-0.

1 DEFINITION

Nilutamide contains NLT 98.0% and NMT 102.0% of nilutamide (C₁₂H₁₀F₃N₃O₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K _{▲(CN 1-May-2020)}

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

PROCEDURE

[NOTE-Throughout the following procedures, protect the sample, the Reference Standard, and solutions containing them by conducting the procedures under subdued light or using low-actinic glassware.]

Buffer: 2.0 g/L of monobasic.potassium phosphate in water. Adjust with a solution of 1 N sodium hydroxide in water to a pH of 7.5.

Mobile phase: Acetonitrile and Buffer (40:60)

Diluent: Acetonitrile and water (35:65)

Standard solution: 0.5 mg/mL of USP Nilutamide RS in Diluent

Sample solution: 0.5 mg/mL of Nilutamide in Diluent

Chromatographic system

(See Chromatography (621), Systern Suitability.)

Mode: LC

Detector: UV 267 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 5 times the retention time of nilutamide

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of nilutarnide (C₁₂H₁₀F₃N₃O₄) in the portion of Nilutamide taken:

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

r_U = peak response of nilutamide from the Sample solution

r_S = peak response of nilutamide from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

Analysis: Use a platinum crucible.

Acceptance criteria: NMT 0.1%

4.2 ORGANIC IMPURITIES

Solution A: 2.0 g/L of monobasic potassium phosphate in water. Adjust with a solution of 1 N sodium hydroxide in water to a pH of 7.5.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (35:65)

System suitability solution: 0.04 mg/mL each of USP Nilutamide RS and USP Flutamide Related Compound A RS in Diluent

Standard solution: 0.002 mg/mL of USP Nilutamide RS in Diluent

Sample solution: 1.0 mg/mL of Nilutamide in Diluent

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between nilutamide and flutamide related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Nilutamide taken:

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of nilutamide from the Standard solution

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

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

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

Table 2

^a 5-Imino-4,4-dimethyl-1-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidin-2-one.

^b 5,5-Dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)oxazolidine-2,4-dione.

^c 1,3-Bis[4-nitro-3-(trifluoromethyl)phenyl]urea.

5 SPECIFIC TESTS

WATER DETERMINATION (921): NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Protect from light. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Flutamide Related Compound A RS

4-Nitro-3-(trifluoromethyl) aniline.

C₂H₅F₃N₂O₂

USP Nilutamide RS