» Chlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C7H6ClN3O4S2.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a peak for chlorothiazide, the retention time of which corresponds to that exhibited by the Standard preparation.
B: Powder 1 Tablet, and fuse it with a pellet of sodium hydroxide: the ammonia fumes produced turn moistened red litmus paper blue, and the residue responds to the test for Sulfite 191.
Medium: 0.05 M pH 8.0 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.
Apparatus 2: 75 rpm.
Time: 60 minutes.
Procedure Determine the amount of C7H6ClN3O4S2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 294 nm of 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 Chlorothiazide RS in the same medium.
Tolerances Not less than 75% (Q) of the labeled amount of C7H6ClN3O4S2 is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements.
Mobile phase Prepare a filtered and degassed solution of 0.08 M monobasic sodium phosphate (adjusted with phosphoric acid to a pH of 2.9 ± 0.1) and methanol (95:5), making adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Transfer an accurately weighed quantity of about 25 mg of USP Chlorothiazide RS to a 50-mL volumetric flask, add 5 mL of 0.05 M monobasic sodium phosphate solution, followed by 10 mL of acetonitrile to the flask, and sonicate with occasional shaking for about 3 minutes. Dilute with water to volume, mix, and filter to obtain a Standard preparation having a known concentration of about 0.5 mg of USP Chlorothiazide RS per mL.
Assay preparation [notePrepare fresh daily. ] Weigh and finely powder not less than 20 Tablets. Weigh accurately a portion of the powder, equivalent to about 250 mg of chlorothiazide, and transfer to a 500-mL volumetric flask. Add 50 mL of 0.05 M monobasic sodium phosphate solution, and shake by mechanical means for about 15 minutes followed by sonication for about 2 minutes. Add 100 mL of acetonitrile, sonicate for about 3 minutes, dilute with water to volume, mix, and filter.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1 and is fitted with a guard column. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure : the capacity factor (k¢) is not less than 4.3; the tailing factor (T) for chlorothiazide is not more than 2.0; the theoretical plate count (N) for chlorothiazide is not less than 1300; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 15 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 C7H6ClN3O4S2 in the portion of Tablets taken by the formula:
500C(rU / rS)in which C is the concentration, in mg per mL, of USP Chlorothiazide 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 2634