Medium: 0.1Nhydrochloric acid;900mL.

Apparatus 1: 50rpm.

Times: 20minutes for captopril;30minutes for hydrochlorothiazide.

Procedure— Determine the amounts of C9H15NO3Sand C7H8ClN3O4S2dissolved,employing the procedure set forth in theAssay.Use filtered portions of the solution under test,suitably diluted withDissolution Medium,if necessary,and compare with a Standard solution having known concentrations of USP Captopril RSand USP Hydrochlorothiazide RSin the same medium.

Tolerances— Not less than 80%(Q)of the labeled amount of captopril (C9H15NO3S)is dissolved in 20minutes,and not less than 60%(Q)of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2)is dissolved in 30minutes.

Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and phosphoric acid (550:450:0.5).Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).

Standard solution— Dissolve an accurately weighed quantity of USP Captopril Disulfide RSinMobile phase,and dilute quantitatively,and stepwise if necessary,withMobile phaseto obtain a solution having a known concentration of about 15µg per mL.

Test solution— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 25mg of captopril,to a 50-mLvolumetric flask,add about 20mLofMobile phase,and sonicate for 15minutes,with occasional shaking.Dilute withMobile phaseto volume,mix,and centrifuge.Use the clear supernatant as theTest solution.

System suitability solution— Prepare a solution inMobile phasecontaining about 0.0075mg per mLof USP Captopril RSand USP Hydrochlorothiazide RS,and 0.015mg per mLof USP Captopril Disulfide RS.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 210-nm detector and a column that contains packing L11.The flow rate is about 2mLper minute.Chromatograph theSystem suitability solution,and record the peak responses as directed underProcedure:the relative retention times are about 0.3for captopril and 1.0for captopril disulfide.The resolution,R,between the captopril and captopril disulfide peaks is not less than 4.0,and both peaks are resolved from the hydrochlorothiazide peak.Chromatograph theStandard solution,and record the peak responses as directed underProcedure:the relative standard deviation for replicate injections is not more than 3.0%.

Procedure— Separately inject equal volumes (about 20µL)of theStandard solutionand theTest solutioninto the chromatograph,record the chromatograms,and measure the responses for the captopril disulfide peaks.Calculate the percentage of captopril disulfide in the portion of Tablets taken by the formula: in whichCis the concentration,in µg per mL,of USP Captopril Disulfide RSin theStandard solution;Wis the quantity,in mg,of captopril in the portion of Tablets taken to prepare theTest solution,based on the labeled amount per Tablet;andrUandrSare the captopril disulfide peak responses obtained from theTest solutionand theStandard solution,respectively:not more than 3.0%is found.

Mobile phase,System suitability solution,and Chromatographic system— Proceed as directed in theAssay.

Standard solution— Dissolve an accurately weighed quantity of USP Benzothiadiazine Related Compound A RSinMobile phase,and dilute quantitatively,and stepwise if necessary,withMobile phaseto obtain a solution having a known concentration of about 10µg per mL.

Test solution— Use theAssay preparation

Procedure— Separately inject equal volumes (about 20µL)of theStandard solutionand theTest solutioninto the chromatograph,record the chromatograms,and measure the responses for the benzothiadiazine related compound Apeaks.Calculate the percentage of benzothiadiazine related compound Ain the portion of Tablets taken by the formula: in whichCis the concentration,in µg per mL,of USP Benzothiadiazine Related Compound A RSin theStandard solution;Wis the quantity,in mg,of hydrochlorothiazide in the portion of Tablets taken to prepare theTest solution,based on the labeled amount per Tablet;andrUandrSare the benzothiadiazine related compound Apeak responses obtained from theTest solutionand theStandard solution,respectively:not more than 1.0%is found.

Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and phosphoric acid (750:250:0.5).Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).

Standard preparation— Dissolve accurately weighed quantities of USP Captopril RSand USP Hydrochlorothiazide RSinMobile phase,and dilute quantitatively,and stepwise if necessary,withMobile phaseto obtain a solution having known concentrations of about 0.3mg of USP Hydrochlorothiazide RSper mLand about 0.3Jmg of USP Captopril RSper mL,Jbeing the ratio of the labeled amount,in mg,of captopril to the labeled amount,in mg,of hydrochlorothiazide per Tablet.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 15mg of hydrochlorothiazide,to a 50-mLvolumetric flask,addMobile phase,and sonicate for 15minutes with occasional shaking.Dilute withMobile phaseto volume,mix,and centrifuge.

System suitability solution— Prepare a solution inMobile phasecontaining about 0.3mg each of USP Captopril RS,USP Hydrochlorothiazide RS,and USP Benzothiadiazine Related Compound A RSper mL.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm ×30-cm column that contains packing L11.The flow rate is about 1.5mLper minute.Chromatograph theSystem suitability solution,and record the peak responses as directed forProcedure:the relative retention times are about 0.4for benzothiadiazine related compound A,0.5for hydrochlorothiazide,and 1.0for captopril.The resolution,R,between the void volume and the benzothiadiazine related compound Apeak is not less than 1.7,the resolution,R,between the benzothiadiazine related compound Aand hydrochlorothiazide peaks is not less than 1.8,and the resolution,R,between the captopril and hydrochlorothiazide peaks is not less than 2.0.Chromatograph theStandard preparation,and record the peak responses as directed underProcedure:the relative standard deviation for replicate injections is not more than 3.0%.

Procedure— Separately inject equal volumes (about 20µL)of theStandard preparationand theAssay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantities,in mg,of captopril (C9H15NO3S)and hydrochlorothiazide (C7H8ClN3O4S2)in the portion of Tablets taken by the formula: in whichCis the concentration,in mg per mL,of the appropriate USP Reference Standard in theStandard preparation;andrUandrSare the responses of the corresponding analyte peaks obtained from theAssay preparationand theStandard preparation,respectively.