A: Infrared Absorption—

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.

Medium: 0.1 N hydrochloric acid; 500 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Mobile phase— Prepare a filtered and degassed mixture of water and acetonitrile (65:35), and add 1 mL of trifluoroacetic acid to each 1 L of the mixture. Adjust with ammonium hydroxide to a pH of 3.0. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard solution— Dissolve an accurately weighed quantity of USP Risperidone RS in Medium, and dilute quantitatively, and stepwise if necessary, with Medium to obtain a solution having a known concentration of about 0.006 mg per mL.

Test solution— Use portions of the solution under test, and pass through a suitable filter having a porosity of 35 µm.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 237-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard solution and the Test solution as directed for Procedure: the retention time of risperidone is about 2.1 minutes, and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of C23H27FN4O2 dissolved by the formula: in which rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of USP Risperidone RS in the Standard solution; 500 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the Tablet label claim in mg.

Tolerances— Not less than 75% (Q) of the labeled amount of C23H27FN4O2 is dissolved in 45 minutes.

Mobile phase and Chromatographic system— Proceed as directed for Dissolution.

Standard solution— Dissolve an accurately weighed quantity of USP Risperidone RS in a suitable volumetric flask, and dilute quantitatively with 0.1 N hydrochloric acid to obtain a solution having a known concentration of about 0.03 mg of risperidone per mL.

Test solution— Transfer one Tablet into a 100-mL volumetric flask, add 50 mL of 0.1 N hydrochloric acid, and shake mechanically for about 30 minutes. Dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of this solution through a suitable filter having a 0.2-µm or finer porosity, and use the filtrate.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the risperidone peak. Calculate the quantitiy, in mg, of risperidone (C23H27FN4O2) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Risperidone RS in the Standard solution; and rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively.

Add the following:

Mobile phase and Diluent— Proceed as directed in the Assay.

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

Diluted sodium hydroxide— To 1 L of water in a beaker, add 0.1 N sodium hydroxide dropwise to obtain a pH of about 8.5.

Diluted hydrogen peroxide— Dilute 1 mL of hydrogen peroxide with water to 500 mL.

Peak identification solution— Suspend 10 mg of USP Risperidone RS in 10 mL of Diluted sodium hydroxide in a 100-mL volumetric flask. Store the flask at 90 for 24 hours. Cool the solution to room temperature. Add 10 mL of aqueous Diluted hydrogen peroxide to the flask, and store at 90 for an additional two hours. Cool the mixture to room temperature, and dilute with methanol to volume.

Test solution— Use the Assay preparation.

Chromatographic system (see Chromatography 621)— Proceed as directed in the Assay. Chromatograph about 20 µL of the Peak identification solution, record the peak responses as directed for Procedure, and identify the peaks using the relative retention times given in Table 1: the resolution, R, between the trans-N-oxide and cis-N-oxide is not less than 1.2. [note—The approximate relative retention times given in Table 1 are for identification purposes only.]

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the responses for all of the peaks. Calculate the percentage of each impurity in the portion of Tablets taken by the formula: in which R is the appropriate relative response factor as listed in Table 1; ri is the peak response for each impurity in the Test solution; and rS is the peak response of risperidone in the Test solution: not more than 0.3% of any individual unidentified impurity is found, not more than 0.5% of any individual specified impurity is found, and not more than 1.0% of total impurities is found.USP31

Diluent— Prepare a degassed mixture of methanol and water (80:20).

Solution A— Prepare a filtered and degassed mixture of water, acetonitrile, and trifluroacetic acid (80:19.5:0.1). Adjust with ammonium hydroxide to a pH of 3.0.

Solution B— Prepare a filtered and degassed mixture of water, methanol, and trifluoroacetic acid (61:39:0.1). Adjust with ammonium hydroxide to a pH of 3.0.

Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Transfer an accurately weighed quantity of USP Risperidone RS to a suitable volumetric flask, and dissolve in and dilute quantitatively with Diluent to obtain a solution having a known concentration of about 0.1 mg per mL.

Assay preparation— Transfer an accurately weighed portion of not fewer than 10 Tablets to a volumetric flask that can accommodate a final concentration of 0.1 mg of risperidone per mL. Add an appropriate amount of water equivalent to 20% of the total volume of the volumetric flask, and mechanically shake for about 30 minutes. Add a volume of methanol equivalent to 60% of the total volume of the volumetric flask, and mechanically shake for about 30 minutes. Dilute with methanol to volume, and mix to obtain the final 0.1 mg per mL concentration. Pass a portion of this solution through a suitable filter having a 0.45-µm or finer porosity, and use the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 2.5 mL per minute. The column is maintained at room temperature. The chromatograph is programmed as follows. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor of risperidone is not more than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.

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 risperidone peak. Calculate the quantity, in mg, of risperidone (C23H27FN4O2) in the portion of Tablets taken by the formula: in which CS is the concentration, in mg per mL, of USP Risperidone RS in the Standard preparation; CU is the concentration, in mg per mL, of risperidone in the Assay preparation; and rU and rS are the peak responses of risperidone obtained from the Assay preparation and the Standard preparation, respectively.