A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, both relative to the internal standard, as obtained in the Assay.

B: Remove the contents of 20 Capsules, and grind the contents to a fine powder. Dissolve a portion of the powder in a mixture of chloroform and methanol (5:1) to obtain a solution containing 3 mg of flutamide per mL. The test solution so obtained responds to the Thin-Layer Chromatographic Identification Test 201, a mixture of chloroform and ethyl acetate (3:1) being used as the developing solvent and 20 µL each of the test solution and the Standard solution being applied to the thin-layer chromatographic plate.

Medium: 2% sodium lauryl sulfate solution; 1000 mL.

Apparatus 2: 75 rpm.

Time: 60 minutes.

Procedure— Determine the amount of C11H11F3N2O3 dissolved from UV absorbances at the wavelength of maximum absorbances at the wavelength of maximum absorbance at about 306 nm on filtered portions of the solution under test, suitably diluted with Dissolution Medium, in comparison with a Standard solution having a known concentration of USP Flutamide RS in the same Medium.

Tolerances— Not less than 75% (Q) of the labeled amount of C11H11F3N2O3 is dissolved in 60 minutes.

Mobile phase— Prepare as directed in the Assay.

Standard solution— Prepare as directed in the Assay for Standard preparation.

Test solution— Use the Assay preparation.

Detector sensitivity solution— Transfer an accurately measured volume of the Standard solution into a volumetric flask, and dilute quantitatively, and stepwise if necessary, with a mixture of water and acetonitrile (4:1) to obtain a solution having a known concentration of about 0.2 µg per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The column temperature is maintained at 25 ± 5. The flow rate is about 1.0 mL per minute. Chromatograph the Detector sensitivity solution, and record the peak area responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 10% for flutamide.

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak area responses. Calculate the percentage of each impurity in the portion of Capsules taken by the formula: in which ri is the peak area response for each impurity, excluding those where peak area responses are less than those obtained from the Detector sensitivity solution; and rs is the sum of the responses of all the peaks: not more than 0.2% for any impurity having a relative retention time of about 0.45 is found; not more than 0.1% of any other impurity is found; and not more than 0.3% of total impurities is found.

(Official January 1, 2007)

Diluent— Prepare a mixture of acetronitrile and water (1:1).

Mobile phase— Prepare a filtered and degassed mixture of water and acetonitrile (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Flutamide RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.5 mg per mL. Transfer 20.0 mL of this solution into a 50-mL volumetric flask, and dilute with water to volume to obtain a final concentration of 0.2 mg per mL.

Assay preparation— Remove the contents of not fewer than 20 Capsules, and mix. Transfer an accurately weighed portion of the powder, equivalent to 125 mg of flutamide, into a 250-mL volumetric flask. Add 180 mL of Diluent. Shake the flask for 15 minutes. Dilute with Diluent to volume, and mix. Allow the insoluble material to settle. Transfer 20.0 mL of supernatant into a 50-mL volumetric flask, dilute with water to volume, mix, and pass through a polytef membrane filter having a 0.45-µm porosity.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The column temperature is maintained at 25 ± 5. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak area response as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak area response for the flutamide peak. Calculate the quantity, in mg, of flutamide (C11H11F3N2O3) in the portion of Capsules taken by the formula: in which C is the concentration, in mg per mL, of USP Flutamide RS in the Standard preparation; and rU and rS are the peak area responses obtained from the Assay preparation and the Standard preparation, respectively.