Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2: 50 rpm.

Time: 30 minutes.

Mobile phase and Chromatographic system—Prepare as directed in the Assay.

procedure for pooled sample— Proceed as directed for Procedure in Apparatus 1 and Apparatus 2, Immediate-Release Dosage Forms under Dissolution 711. Combine equal volumes of the filtered solutions of the 6 or 12 individual specimens withdrawn, and use the pooled sample as the test solution. Inject a volume of the pooled sample into the chromatograph, record the chromatogram, and measure the response for the major peak. Calculate the quantity of C21H31N3O5 dissolved in comparison with a Standard solution having a known concentration of USP Lisinopril RS in the same Medium and similarly chromatographed.

Tolerances— Not less than 80% (Q) of the labeled amount of C21H31N3O5 in the Tablets is dissolved in 30 minutes: the requirements are met if the quantities of active ingredient dissolved from the pooled sample conform to the accompanying Acceptance Table for a Pooled Sample. Continue testing through the three stages unless the results conform at either S1 or S2. The quantity, Q, is the amount of dissolved active ingredient specified, expressed as a percentage of the labeled content.

procedure for unit sample— Proceed as directed for Procedure in Apparatus 1 and Apparatus 2, Immediate-Release Dosage Forms under Dissolution 711. Inject a volume of a filtered portion of the solution under test into the chromatograph, record the chromatogram, and measure the response for the major peak. Calculate the amount of C21H31N3O5 dissolved in comparison with a Standard solution having a known concentration of USP Lisinopril RS in the Medium and similarly chromatographed.

Tolerances— Not less than 80% (Q) of the labeled amount of C21H31N3O5 is dissolved in 30 minutes.

Procedure for content uniformity—

Phosphate solution, Mobile phase, and Chromatographic system— Prepare as directed in the Assay.

Diluent— Dissolve 2.72 g of monobasic potassium phosphate in 800 mL of water, adjust with phosphoric acid to a pH of 4.0, dilute with water to 1000 mL, and mix.

Standard preparation— Dissolve an accurately weighed quantity of USP Lisinopril RS in Diluent to obtain a solution having a known concentration of about 0.2 mg per mL.

Test preparation— Place one Tablet in a volumetric flask of appropriate size, based on the labeled quantity, in mg, of lisinopril in the Tablet, to obtain a solution containing 0.2 mg of lisinopril per mL. Fill the flask to about 50% volume with Diluent, sonicate for 5 minutes, and shake by mechanical means for 20 minutes. Dilute with Diluent to volume, mix, and filter.

Procedure— [note—Use peak areas where peak responses are indicated.] Separately inject equal volumes (about 20 µL) of the Test preparation and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C21H31N3O5 in the Tablet taken by the formula: in which T is the labeled quantity, in mg, of lisinopril in the Tablet; C is the concentration, in mg per mL, calculated on the anhydrous basis, of USP Lisinopril RS in the Standard preparation; D is the concentration, in mg per mL, of lisinopril in the Test preparation, based upon the labeled quantity per Tablet and the extent of dilution; and rU and rS are the lisinopril peak responses obtained from the Test preparation and the Standard preparation, respectively.

Phosphate solution, Mobile phase, Diluent, and Chromatographic system— Prepare as directed in the Assay.

Standard solution— Dilute the Standard preparation, prepared as directed in the Assay, with Diluent to obtain a solution having a known concentration of about 20 µg per mL.

Test solution— Use the Assay preparation.

Procedure— Proceed as directed in the Assay. Measure the responses of the lisinopril peak obtained from the Standard solution, and of all peaks other than that of lisinopril obtained from the Test solution. Calculate the percentage of related compounds in each Tablet taken by the formula: in which V is the volume, in mL, of the Test solution; C is the concentration, in mg per mL, calculated on the anhydrous basis, of USP Lisinopril RS in the Standard solution; L is the quantity, in mg, of lisinopril in each Tablet, taken as determined in the Assay; rU is the sum of all peak responses other than that of lisinopril obtained from the Test solution; and rS is the lisinopril peak response obtained from the Standard solution: not more than 2.0%, calculated on the basis of the quantity, in mg, of lisinopril in the portion of Tablets taken, as determined in the Assay, is found.

Phosphate solution— Dissolve 4.1 g of monobasic potassium phosphate in about 900 mL of water in a 1000-mL volumetric flask, and adjust with phosphoric acid to a pH of 2.0. Dilute with water to volume, and mix.

Mobile phase— Dissolve 1.0 g of sodium 1-hexanesulfonate in 820 mL of Phosphate solution. Add 180 mL of acetonitrile, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Prepare a mixture of water and methanol (4:1).

Standard preparation— Dissolve an accurately weighed quantity of USP Lisinopril RS in Diluent to obtain a solution having a known concentration of about 0.2 mg per mL.

Assay preparation— Transfer to a suitable size volumetric flask 10 Tablets, which when diluted with Diluent will yield a solution having a concentration of about 0.2 mg per mL. Add Diluent, and sonicate for 5 minutes. Shake the flask by mechanical means for 20 minutes, dilute with Diluent to volume, mix, and filter.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 20-cm column that contains packing L7 and is maintained at a temperature of 40. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the analyte peak is not less than 700 theoretical plates; the tailing factor for the analyte peak is not more than 2.0; the capacity factor, k¢, for the analyte peak is greater than 1.5; and the relative standard deviation for replicate injections is not more than 2%.

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 area responses for the major peaks. Calculate the quantity, in mg, of C21H31N3O5 in each Tablet taken by the formula: in which L is the labeled quantity, in mg, of lisinopril in each Tablet, D is the concentration, in mg per mL, of lisinopril in the Assay preparation based on the labeled quantity per Tablet and the extent of dilution; C is the concentration, in mg per mL, calculated on the anhydrous basis, of USP Lisinopril RS in the Standard preparation; and rU and rS are the lisinopril peak area responses obtained from the Assay preparation and the Standard preparation, respectively.