Bicalutamide

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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Bicalutamide

C₁₈H₁₄F₄N₂O₄S 430.37

Propanamide, N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-, (±)-;

(±)-4′-Cyano-α,α,α-trifluoro-3-[(p-fluorophenyl)sulfonyl]-2-methyl-m-lactotoluidide

CAS RN®: 90357-06-5; UNII: A0Z3NAU9DP.

1 DEFINITION

Bicalutamide contains NLT 98.0% and NMT 102.0% of C₁₈H₁₄F₄N₂O₄S, calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (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

Solution A: 0.01% (v/v) of trifluoroacetic acid in water

Solution B: 0.01% (v/v) of trifluoroacetic acid in acetonitrile

Mobile phase: Solution A and Solution B (52:48)

Diluent: Solution A and Solution B (1:2)

System suitability solution: 5 µg/mL of USP Bicalutamide Related Compound A RS and 50 µg/mL of USP Bicalutamide RS in Diluent

Standard solution: 0.05 mg/mL of USP Bicalutamide RS in Diluent

Sample solution: 0.05 mg/mL of Bicalutamide in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.0-mm × 10-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for bicalutamide related compound A isomer A and bicalutamide related compound A isomer B are 0.75 and 0.78, respectively.]

Suitability requirements

Resolution: NLT 2.0 between bicalutamide related compound A isomer B and bicalutamide, System suitability solution

Relative standard deviation: NMT 2%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₈H₁₄F₄N₂O₄S in the portion of Bicalutamide taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Bicalutamide RS in the Standard solution (mg/mL)

Cᵤ = concentration of the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Solution A, Solution B, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Mobile phase: See the gradient table below.

Standard solution: 1 µg/mL of USP Bicalutamide RS in Diluent

Sample solution: 1 mg/mL of Bicalutamide in Diluent

System suitability

Sample: System suitability solution

Suitability requirements

Resolution 1: NLT 0.8 between bicalutamide related compound A isomer A and bicalutamide related compound A isomer B

Resolution 2: NLT 8.5 between bicalutamide related compound A isomer B and bicalutamide

Analysis

Samples: Standard solution and Sample solution

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

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak area of each impurity from the Sample solution

rₛ = peak area of bicalutamide from the Standard solution

Cₛ = concentration of bicalutamide in the Standard solution (mg/mL)

Cᵤ = concentration of Bicalutamide in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.5%

a. 4-Amino-2-(trifluoromethyl)benzonitrile.

b. N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide.

c. N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methyl-3-(phenylsulfonyl)propanamide.

d. N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-(2-fluorophenylsulfonyl)-2-hydroxy-2-methylpropanamide.

e. N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenylsulfonyl)-2-methylpropanamide.

f. N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenylthio)-2-hydroxy-2-methylpropanamide.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Bicalutamide RS

USP Bicalutamide Related Compound A RS

[N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide]

(C₁₈H₁₄F₄N₂O₃S 414.37)