Captopril and Hydrochlorothiazide Tablets
» Captopril and Hydrochlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of captopril (C9H15NO3S) and hydrochlorothiazide (C7H8ClN3O4S2).
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Benzothiadiazine Related Compound A RS Click to View Structure
4-Amino-6-chloro-1,3-benzenedisulfonamide.
    C6H8ClN3O4S2    285.73
USP Captopril RS Click to View Structure
USP Captopril Disulfide RS
USP Hydrochlorothiazide RS Click to View Structure
Identification— The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those of the Standard preparation obtained as directed in the Assay.
Dissolution 711
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 50 rpm.
Times: 20 minutes for captopril; 30 minutes for hydrochlorothiazide.
Procedure— Determine the amounts of C9H15NO3S and C7H8ClN3O4S2 dissolved, employing the procedure set forth in the Assay. Use filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, and compare with a Standard solution having known concentrations of USP Captopril RS and USP Hydrochlorothiazide RS in the same medium.
Tolerances— Not less than 80% (Q) of the labeled amount of captopril (C9H15NO3S) is dissolved in 20 minutes, and not less than 60% (Q) of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2) is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Limit of captopril disulfide—
Mobile phase— Prepare a filtered and degassed mixture of water, methanol, and phosphoric acid (550:450:0.5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Dissolve an accurately weighed quantity of USP Captopril Disulfide RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 15 µg per mL.
Test solution— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 25 mg of captopril, to a 50-mL volumetric flask, add about 20 mL of Mobile phase, and sonicate for 15 minutes, with occasional shaking. Dilute with Mobile phase to volume, mix, and centrifuge. Use the clear supernatant as the Test solution.
System suitability solution— Prepare a solution in Mobile phase containing about 0.0075 mg per mL of USP Captopril RS and USP Hydrochlorothiazide RS, and 0.015 mg per mL of USP Captopril Disulfide RS.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 210-nm detector and a column that contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed under Procedure: the relative retention times are about 0.3 for captopril and 1.0 for 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 the Standard solution, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 3.0%.
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 responses for the captopril disulfide peaks. Calculate the percentage of captopril disulfide in the portion of Tablets taken by the formula:
(5C/W)(rU / rS)
in which C is the concentration, in µg per mL, of USP Captopril Disulfide RS in the Standard solution; W is the quantity, in mg, of captopril in the portion of Tablets taken to prepare the Test solution, based on the labeled amount per Tablet; and rU and rS are the captopril disulfide peak responses obtained from the Test solution and the Standard solution, respectively: not more than 3.0% is found.
Limit of benzothiadiazine related compound A—
Mobile phase, System suitability solution, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Benzothiadiazine Related Compound A RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 10 µg per mL.
Test solution— Use the Assay preparation
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 responses for the benzothiadiazine related compound A peaks. Calculate the percentage of benzothiadiazine related compound A in the portion of Tablets taken by the formula:
(5C/W)(rU / rS)
in which C is the concentration, in µg per mL, of USP Benzothiadiazine Related Compound A RS in the Standard solution; W is the quantity, in mg, of hydrochlorothiazide in the portion of Tablets taken to prepare the Test solution, based on the labeled amount per Tablet; and rU and rS are the benzothiadiazine related compound A peak responses obtained from the Test solution and the Standard solution, respectively: not more than 1.0% is found.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of water, methanol, and phosphoric acid (750:250:0.5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve accurately weighed quantities of USP Captopril RS and USP Hydrochlorothiazide RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having known concentrations of about 0.3 mg of USP Hydrochlorothiazide RS per mL and about 0.3J mg of USP Captopril RS per mL, J being 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 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 15 mg of hydrochlorothiazide, to a 50-mL volumetric flask, add Mobile phase, and sonicate for 15 minutes with occasional shaking. Dilute with Mobile phase to volume, mix, and centrifuge.
System suitability solution— Prepare a solution in Mobile phase containing about 0.3 mg each of USP Captopril RS, USP Hydrochlorothiazide RS, and USP Benzothiadiazine Related Compound A RS per mL.
Chromatographic system (see Chromatography 621)— 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 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.4 for benzothiadiazine related compound A, 0.5 for hydrochlorothiazide, and 1.0 for captopril. The resolution, R, between the void volume and the benzothiadiazine related compound A peak is not less than 1.7, the resolution, R, between the benzothiadiazine related compound A and 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 the Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 3.0%.
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 major peaks. Calculate the quantities, in mg, of captopril (C9H15NO3S) and hydrochlorothiazide (C7H8ClN3O4S2) in the portion of Tablets taken by the formula:
50C(rU / rS)
in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and rU and rS are the responses of the corresponding analyte peaks obtained from the Assay preparation and the Standard preparation, respectively.
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