Bicalutamide Tablets

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

Bicalutamide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S).

2 IDENTIFICATION

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Mobile phase: Acetonitrile, tetrahydrofuran, and water (15:20:65)

System suitability stock solution: 0.8 mg/mL of USP Bicalutamide RS and 0.4 mg/mL of USP Bicalutamide Related Compound B RS in tetrahydrofuran

System suitability solution: 0.04 mg/mL of USP Bicalutamide RS and 0.02 mg/mL of USP Bicalutamide Related Compound B RS from the system suitability stock solution in Mobile phase

Standard stock solution: 0.8 mg/mL of USP Bicalutamide RS in tetrahydrofuran

Standard solution: 0.04 mg/mL of USP Bicalutamide RS from the standard stock solution in Mobile phase

Sample stock solution: Nominally 0.5 mg/mL of bicalutamide from Tablets in tetrahydrofuran prepared as follows. Transfer an equivalent to 50 mg of bicalutamide from finely powdered Tablets (NLT 20) into a 100-mL volumetric flask. Add 50 mL of tetrahydrofuran, and sonicate for NLT 10 min to complete dissolution. Allow to cool to room temperature, and dilute with tetrahydrofuran to volume. Pass through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 0.04 mg/mL of bicalutamide from the sample stock solution in Mobile phase.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm. For Identification B, use a diode array detector in the range of 190–400 nm.

Column: 5-mm × 12.5-cm; 3-µm packing L1

Column temperature: 50°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 1.5 times the retention time of bicalutamide

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for bicalutamide and bicalutamide related compound B are 1.0 and 1.1, respectively.]

Suitability requirements

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

Tailing factor: NMT 1.2, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak area of bicalutamide from the Sample solution

rₛ = peak area of bicalutamide from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 10 mg/mL of sodium lauryl sulfate in water; 1000 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: 0.05 mg/mL of USP Bicalutamide RS in Medium prepared as follows. Transfer an appropriate amount of USP Bicalutamide RS to a suitable volumetric flask, dissolve in tetrahydrofuran equivalent to 1% of the final volume, and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 270 nm

Path length: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) dissolved:

Result = (Aᵤ/Aₛ) × Cₛ × V × (1/L) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

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

V = volume of Medium (mL)

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: 10 mg/mL of sodium lauryl sulfate in water; 1000 mL

Apparatus 2: 50 rpm

Time: 45 min

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

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Instrumental conditions and analysis: Same as Test 1

Tolerances: NLT 75% (Q) of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) is dissolved.

Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.

Medium: 10 mg/mL of sodium lauryl sulfate in water; 1000 mL

Apparatus 2: 75 rpm

Time: 60 min

Standard solution: 0.01 mg/mL of USP Bicalutamide RS in Medium, sonicate to aid dissolution.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Discard the first few milliliters of the filtrate. Dilute with Medium to a concentration that is similar to that of the Standard solution.

Instrumental conditions: Same as Test 1

Tolerances: NLT 80% (Q) of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

Procedure for content uniformity

Diluent: 10 mg/mL of sodium lauryl sulfate in water

Standard solution: 0.05 mg/mL of USP Bicalutamide RS in Diluent. Dissolve USP Bicalutamide RS in a minimum volume of tetrahydrofuran before dilution with Diluent.

Sample stock solution: Nominally 0.5 mg/mL of bicalutamide prepared as follows. Transfer 1 Tablet to a 100-mL volumetric flask. Add 10 mL of water, and sonicate for approximately 30 min. Add 80 mL of tetrahydrofuran, and sonicate for 30 min to complete dissolution of bicalutamide. Allow to cool to room temperature, and dilute with tetrahydrofuran to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 0.05 mg/mL of bicalutamide prepared as follows. Transfer 10.0 mL of the Sample stock solution into a 100-mL volumetric flask, and dilute with Diluent to volume.

Instrumental conditions: Same as Test 1

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of bicalutamide (C₁₈H₁₄F₄N₂O₄S) in the Tablet taken:

Result = (Aᵤ/Aₛ) × (Cₛ/Cᵤ) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

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

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

5 IMPURITIES

Limit of Bicalutamide Aminobenzonitrile

Mobile phase, system suitability stock solution, and system suitability solution: Prepare as directed in the Assay.

Standard stock solution: 0.2 mg/mL of USP Bicalutamide RS in tetrahydrofuran

Standard solution: 0.02 mg/mL of USP Bicalutamide RS from the standard stock solution in Mobile phase

Sample solution: Nominally 2 mg/mL of bicalutamide from Tablets prepared as follows. Transfer the equivalent to 50 mg of bicalutamide from powdered Tablets (NLT 20) to a 25-mL volumetric flask. Add 2 mL of tetrahydrofuran, and allow to stand for 5 min. Add 20 mL of Mobile phase, sonicate for 10 min, and allow to cool to room temperature. Dilute with Mobile phase to volume, and pass through a suitable filter of 0.2-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 5-mm × 12.5-cm; 3-µm packing L1

Column temperature: 50°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of bicalutamide

System suitability

Sample: System suitability solution

[Note—The relative retention times of bicalutamide aminobenzonitrile, bicalutamide, and bicalutamide related compound B are about 0.4, 1.0, and about 1.1, respectively.]

Suitability requirements

Resolution: NLT 2.0 between bicalutamide and bicalutamide related compound B

Tailing factor: NMT 1.2 for bicalutamide

Relative standard deviation: NMT 2.0% for bicalutamide

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bicalutamide aminobenzonitrile in the portion of Tablets taken:

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

rᵤ = peak area of bicalutamide aminobenzonitrile from the Sample solution

rₛ = peak area of bicalutamide from the Standard solution

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

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

F = relative response factor for bicalutamide aminobenzonitrile, 1.4

Acceptance criteria: NMT 0.1%

6 ADDITIONAL REQUIREMENTS

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

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Bicalutamide RS

USP Bicalutamide Related Compound B RS

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

Also known as (RS)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(3-fluorophenylsulfonyl)-2-hydroxy-2-methylpropanamide.

C₁₇H₁₁F₄N₂O₃S 430.37