A:Infrared Absorption á197Kñ.

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

Test solution: 20mg per mL,in methanol.

Standard stock solution— Transfer about 50mLof dimethylformamide to a 200-mLvolumetric flask.Add about 75mg each of acetone and acetonitrile and 30mg each of methylene chloride and toluene,each accurately weighed by difference,and mix.Dilute with dimethylformamide to volume,and mix.

System suitability solution 1— Transfer about 25mLof dimethylformamide to a 50-mLvolumetric flask.Add 35µLof dehydrated alcohol and 25µLof methylene chloride.Dilute with dimethylformamide to volume,and mix.Transfer 1.0mLof this solution to a 50-mLvolumetric flask,dilute with dimethylformamide to volume,and mix.

System suitability solution 2— Transfer 2.0mLof the Standard stock solutionto a 50-mLvolumetric flask,dilute with dimethylformamide to volume,and mix.

Standard solution— Transfer 4.0mLof the Standard stock solutionto a 50-mLvolumetric flask,dilute with dimethylformamide to volume,and mix.

Test solution— Transfer about 60mg of Quinapril Hydrochloride,accurately weighed,to a suitable headspace vial,add 5.0mLof dimethylformamide,seal,and shake to dissolve.

Chromatographic system (see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector,a headspace sampler,a 0.53-mm ×30-m fused-silica column coated with a 1.0-µm film of phase G16,and a split injection system.The carrier gas is helium,flowing at a rate of 6mLper minute.The split flow rate is about 100mLper minute,with a back pressure of 3.5psi.The oven temperature of the headspace sampler is maintained at 60,and the vial pressure is maintained at 6.1psi.The temperature of the headspace loop and transfer lines is maintained at 65.The vials are equilibrated for 10minutes prior to injection,and injection occurs every 36minutes.The chromatograph is programmed as follows.Initially the column temperature is maintained at 35for 10minutes,then the temperature is increased at a rate of 7per minute to 150,and maintained at 150for 4minutes.The injection port temperature is maintained at 180,and the detector is maintained at 240.Chromatograph System suitability solution 1,and record the peak responses as directed for Procedure:the relative retention times are about 0.94for methylene chloride and 1.0for alcohol;the resolution,R,between methylene chloride and alcohol is not less than 1.2;the column efficiency,determined from the methylene chloride peak,is not less than 4900theoretical plates;and the tailing factor for the methylene chloride peak is not more than 1.7.Chromatograph System suitability solution 2,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 15.0%.

Procedure— Separately inject equal volumes (about 1mL)of the gaseous headspace of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Separately calculate the percentages,by weight,of acetone,acetonitrile,methylene chloride,and toluene in the portion of Quinapril Hydrochloride taken by the formula: in which WSis the weight,in mg,of the appropriate solvent taken to prepare the Standard solution;WQis the weight,in mg,of Quinapril Hydrochloride taken to prepare the Test solution;and rUand rSare the peak responses of the relevant solvent obtained from the Test solutionand the Standard solution,respectively:not more than 0.25%each of acetone and acetonitrile is found;and not more than 0.1%each of methylene chloride and toluene is found.

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

System suitability solution— Prepare as directed for the System suitability preparation in the Assay.

Standard solution— Dissolve accurately weighed quantities of USP Quinapril Related Compound A RSand USP Quinapril Related Compound B RSin Diluentto obtain a solution having known concentrations of about 0.5mg of each per mL.Transfer 1.0mLof this solution to a 100-mLvolumetric flask,dilute with Diluentto volume,and mix.

Test solution— Use the Assay preparation.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the percentage of each quinapril related compound in the portion of Quinapril Hydrochloride taken by the formula: in which VUis the volume,in mL,of the Test solution;WUis the weight,in mg,of Quinapril Hydrochloride taken to prepare the Test solution;CSis the concentration,in mg per mL,of the relevant USP Reference Standard in the Standard solution;and rUand rSare the peak areas of the corresponding quinapril related compound obtained from the Test solutionand the Standard solution,respectively:not more than 0.5%each of quinapril related compound Aand quinapril related compound Bis found.Calculate the percentage of each impurity in the portion of Quinapril Hydrochloride taken by the formula: in which riis the peak response for each impurity obtained from the Test solution;and rsis the sum of the responses of all the peaks obtained from the Test solution:not more than 0.2%of any individual impurity,other than quinapril related compound Aand quinapril related compound B,is found;and not more than 2.0%of total impurities is found.

Diluent— Prepare a mixture of pH6.5,0.025Mmonobasic ammonium phosphate solution and acetonitrile (3:2).

Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,and methanesulfonic acid (72:28:0.1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

System suitability preparation— Dissolve accurately weighed quantities of USP Quinapril Hydrochloride RS,USP Quinapril Related Compound A RS,and USP Quinapril Related Compound B RSin Diluentto obtain a solution having known concentrations of about 2mg of USP Quinapril Hydrochloride RSper mLand 0.005mg each of USP Quinapril Related Compound A RSand USP Quinapril Related Compound B RSper mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Quinapril Hydrochloride RSin Diluentto obtain a solution having a known concentration of about 2mg per mL.

Assay preparation— Transfer about 100mg of Quinapril Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Diluentto volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector,a 4.6-mm ×3-cm guard column that contains 5-µm packing L10,and a 4.6-mm ×25-cm column that contains 5-µm packing L10.The flow rate is about 1.5mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the resolution between quinapril and quinapril related compound Ais not less than 1.75;the resolution between quinapril and quinapril related compound Bis not less than 3.5;the column efficiency is not less than 550theoretical plates;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the quinapril hydrochloride peaks.Calculate the quantity,in mg,of C25H30N2O5·HCl in the portion of Quinapril Hydrochloride taken by the formula: in which Cis the concentration,in mg per mL,of USP Quinapril Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.