» Hydrochlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2).
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: Transfer a portion of finely powdered Tablets, equivalent to about 50 mg of hydrochlorothiazide, to a 50-mL volumetric flask. Add about 20 mL of sodium hydroxide solution (1 in 125), and shake vigorously for 15 minutes. Dilute with the same solvent to volume, mix, and filter, discarding the first few mL of the filtrate. Transfer 5 mL of the filtrate to a 125-mL separator, and add 5 mL of dilute hydrochloric acid (1 in 10). Extract with 50 mL of ether, filter the ether extract through a small, dry, folded filter paper, and evaporate to dryness. Add 5 mL of alcohol, and again evaporate to dryness: the IR absorption spectrum of a potassium bromide dispersion of the residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Hydrochlorothiazide RS previously dissolved in alcohol and recovered by evaporating the solution to dryness.
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: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 100 rpm.
Time: 60 minutes.
Procedure Determine the amount of C7H8ClN3O4S2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 272 nm on filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Hydrochlorothiazide RS in the same Medium.
Tolerances Not less than 60% (Q) of the labeled amount of C7H8ClN3O4S2 is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements.
Mobile phase, System suitability solution, and Chromatographic system Proceed as directed in the Assay.
Test solution Proceed as directed for Assay preparation in the Assay.
Standard solution [noteA volume of acetonitrile not exceeding 10% of the total volume of the solution may be used to dissolve the USP Reference Standard. ] Dissolve an accurately weighed quantity of USP Benzothiadiazine Related Compound A RS in Mobile phase to obtain a solution having a known concentration of about 1.5 µg per mL.
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 major peaks. Calculate the quantity, in mg, of benzothiadiazine related compound A in the portion of tablets taken by the formula:
0.2C(rU / rS)in which C is the concentration, in µg per mL, of USP Benzothiadiazine Related Compound A RS in the Standard solution; and rU and rS are the peak responses for benzothiadiazine related compound A obtained from the Test solution and the Standard solution, respectively: not more than 1.0% is present.
Mobile phase Prepare a degassed mixture of 0.1 M monobasic sodium phosphate and acetonitrile (9:1), adjust with phosphoric acid to a pH of 3.0 ± 0.1, and filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution [noteA volume of acetonitrile not exceeding 10% of the total volume of solution may be used to dissolve the USP Reference Standards. ] Dissolve accurately weighed quantities of chlorothiazide and USP Hydrochlorothiazide RS in Mobile phase to obtain a solution containing about 0.15 mg of each per mL.
Standard preparation [noteA volume of acetonitrile not exceeding 10% of the total volume of the solution may be used to dissolve the USP Reference Standard. ] Dissolve an accurately weighed quantity of USP Hydrochlorothiazide RS in Mobile phase to obtain a solution having a known concentration of about 0.15 mg per mL.
Assay preparation Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 30 mg of hydrochlorothiazide, to a 200-mL volumetric flask. Add about 20 mL of Mobile phase, sonicate for 5 minutes, and add about 20 mL of acetonitrile. Sonicate for 5 minutes, add about 50 mL of Mobile phase, and shake by mechanical means for 10 minutes. Dilute with Mobile phase to volume, mix, and filter, discarding the first 10 mL of the filtrate.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for chlorothiazide and 1.0 for hydrochlorothiazide; and the resolution, R, between chlorothiazide and hydrochlorothiazide is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.5%.
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 quantity, in mg, of hydrochlorothiazide (C7H8ClN3O4S2) in the portion of Tablets taken by the formula:
200C(rU / rS)in which C is the concentration, in mg per mL, of USP Hydrochlorothiazide RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3424Pharmacopeial Forum: Volume No. 28(6) Page 1745