A: Thin-Layer Chromatographic Identification Test 201—

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: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 30 minutes.

Procedure— Determine the amount of C25H30N2O5 dissolved by employing the procedure set forth in the Assay, using a filtered portion of the solution under test as the Assay preparation, using methanol to prepare the Standard preparation, and making any necessary volumetric adjustments with water.

Tolerances— Not less than 80% (Q) of the labeled amount of C25H30N2O5 is dissolved in 30 minutes.

PROCEDURE FOR CONTENT UNIFORMITY—

Solvent, Buffered solvent, and Mobile phase— Prepare as directed in the Assay.

Resolution solution— Dissolve accurately weighed quantities of USP Quinapril Hydrochloride RS, USP Quinapril Related Compound A RS, and USP Quinapril Related Compound B RS in Solvent to obtain a solution having known concentrations of about 0.1 mg of USP Quinapril Hydrochloride RS and 0.005 mg each of USP Quinapril Related Compound A RS and USP Quinapril Related Compound B RS per mL.

Standard solution— Dissolve accurately weighed quantities of USP Quinapril Related Compound A RS and USP Quinapril Related Compound B RS in Solvent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having known concentrations of about 0.5 µg each of USP Quinapril Related Compound A RS and USP Quinapril Related Compound B RS per mL.

Test solution— Use the Assay preparation.

Chromatographic system— Prepare as directed in the Assay. Chromatograph the Resolution solution, and record the peak areas as directed for Procedure: the relative retention times are about 0.6 for quinapril related compound B, 1.0 for quinapril, and 2.0 for quinapril related compound A; and the resolution, R, between quinapril and quinapril related compound A and between quinapril and quinapril related compound B is not less than 2.0. Chromatograph the Standard solution, and record the peak areas as directed for Procedure: the column efficiency is not less than 600 theoretical plates; the tailing factor for the quinapril and quinapril related compound A peaks is less than 1.5 and that for the quinapril related compound B peak is less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0% for quinapril and not more than 3.0% for each quinapril related compound.

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 of the major peaks. Calculate the quantity, in mg, of each quinapril related compound in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard solution; D is the dilution factor used to prepare the Test solution; and rU and rS are the peak areas of the corresponding quinapril related compound obtained from the Test solution and the Standard solution, respectively: not more than 1.0% of quinapril related compound A is found; not more than 3.0% of quinapril related compound B is found; and not more than 3.6% of total impurities is found.

(Official January 1, 2007)

Solvent— Prepare a mixture of water and acetonitrile (65:35).

Buffered solvent— Prepare a mixture of pH 6.5, 0.05 M dibasic potassium phosphate and acetonitrile (65:35).

Mobile phase— Prepare a filtered and degassed mixture of water, acetonitrile, and methanesulfonic acid (65:35:0.2). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Quinapril Hydrochloride RS in Solvent to obtain a solution having a known concentration of about 1.08 mg per mL. Quantitatively dilute with Buffered solvent to obtain a solution having a known concentration of about 0.108 mg per mL.

Assay preparation— Transfer 10 Tablets to a 500-mL volumetric flask, add about 300 mL of Solvent, and sonicate until the Tablets have disintegrated. Shake by mechanical means for about 15 minutes, dilute with Solvent to volume, mix, and centrifuge. Dilute quantitatively, and stepwise if necessary, with Solvent to obtain a solution having a concentration of about 0.1 mg of quinapril per mL; and pass through a suitable filter, discarding the first portion of the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 214-nm detector and a 6.0-mm × 4-cm column that contains 3-µm packing L10. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the column efficiency is not less than 600 theoretical plates; the tailing factor is not more than 1.5; 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 areas for the major peaks. Calculate the quantity, in mg, of quinapril (C25H30N2O5) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Quinapril Hydrochloride RS in the Standard preparation; D is the dilution factor used to prepare the Assay preparation; 438.52 and 474.98 are the molecular weights of quinapril and quinapril hydrochloride, respectively; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.