A: Infrared Absorption 197M.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Mobile phase and System suitability solution— Prepare as directed in the Assay.

Standard solution— Use the Standard preparation, prepared as directed in the Assay.

Test solution— Use the Assay preparation, prepared as directed in the Assay.

Detector sensitivity solution— Transfer 1.0 mL of the Standard solution into a 100-mL volumetric flask, dilute with a mixture of water and acetonitrile (4:1) to volume, and mix. 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 0.1 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 System suitability solution, and record the peak area responses as directed for Procedure: the relative retention times are about 1.4 for o-flutamide and 1.0 for flutamide; and the resolution, R, between flutamide and o-flutamide is not less than 6.0. 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 10.0% 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 Flutamide taken by the formula: in which F is the relative response factor of the impurities according to the table below; ri is the peak area response for each impurity; and rs is the sum of the responses of all the peaks: the impurities meet the requirements tabulated below.

(Official January 1, 2007)

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 50 mL of acetonitrile, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.2 mg per mL.

System suitability solution— Transfer about 50 mg of USP o-Flutamide RS, accurately weighed, to a 50-mL volumetric flask, dissolve in 10 mL of acetonitrile, dilute with water to volume, and mix. Transfer 1.0 mL of this solution and 5.0 mL of the Standard preparation into a 100-mL volumetric flask, dilute with a mixture of water and acetonitrile (4:1) to volume, and mix.

Assay preparation— Transfer about 50 mg of Flutamide, previously dried and accurately weighed, to a 250-mL volumetric flask. Add 50 mL of acetonitrile, and sonicate until the Flutamide dissolves. Add 150 mL of water, mix, and allow to warm to room temperature. Dilute with water to volume, and mix.

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 System suitability solution, and record the peak area responses as directed for Procedure: the relative retention times are about 1.4 for o-flutamide and 1.0 for flutamide; and the resolution, R, between flutamide and o-flutamide is not less than 6.0. Chromatograph the Standard preparation, and record the peak area responses 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 responses for the major peaks. Calculate the quantity, in mg, of C11H11F3N2O3 in the portion of Flutamide 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.