Methyldopa and Hydrochlorothiazide Tablets
» Methyldopa and Hydrochlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of methyldopa (C10H13NO4) and hydrochlorothiazide (C7H8ClN3O4S2).
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: The retention times of the 2 major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation as obtained in the Assay.
B: A portion of crushed Tablets, equivalent to about 10 mg of methyldopa, responds to Identification test C under Methyldopa.
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Times: 30 minutes; 60 minutes.
procedure for methyldopa
Standard preparation Dissolve an accurately weighed quantity of USP Methyldopa RS in Medium, and dilute quantitatively with the same solvent to obtain a solution having a known concentration of about 275 µg of anhydrous methyldopa per mL.
Ferrous tartrate solution Dissolve 1 g of ferrous sulfate, 2 g of potassium sodium tartrate, and 100 mg of sodium bisulfite in water to make 100 mL. Use a freshly prepared solution.
Buffer solution Dissolve 50 g of ammonium acetate in 1000 mL of dilute alcohol (1 in 5). Adjust with 6 N ammonium hydroxide to a pH of 8.5.
Procedure Filter 35 mL of the solution under test through paper, and transfer an aliquot estimated to contain between 2 mg and 3 mg of methyldopa into a 100-mL volumetric flask. Adjust the final volume, if necessary, with Medium to 10 mL. To a second 100-mL volumetric flask add 10.0 mL of Standard preparation, and to a third 100-mL volumetric flask add 10.0 mL of Medium to provide a blank. Treat each flask as follows: Add by pipet 5 mL of Ferrous tartrate solution and, dilute with Buffer solution to volume. Concomitantly determine the absorbances of the treated Standard preparation and test solution in 1-cm cells at the wavelength of maximum absorbance at about 520 nm, with a suitable spectrophotometer, against the reagent blank. Calculate the amount of C10H13NO4 dissolved, in mg, taken by the formula:
9(C / V)(AU / AS)in which C is the concentration, in µg of anhydrous methyldopa per mL, of USP Methyldopa RS in the Standard preparation; V is the volume, in mL, of the aliquot of test solution used; and AU and AS are the absorbances of the solutions from the test solution and the Standard preparation, respectively.
procedure for hydrochlorothiazide Determine the amount of C7H8ClN3O4S2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 317 nm in 1-cm cells, of filtered portions of the solution under test, suitably diluted with Dissolution Medium, in comparison with a Standard solution having a known concentration of USP Hydrochlorothiazide RS in the same medium.
Tolerances Not less than 80% (Q) of the labeled amount of methyldopa (C10H13NO4) is dissolved in 30 minutes, and not less than 80% (Q) of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2) is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements with respect to methyldopa and to hydrochlorothiazide.
Procedure for content uniformity Proceed as directed in the Assay, except use the following Test preparation instead of the Assay preparation.
Test preparation Transfer 1 Tablet to a 250-mL volumetric flask, add 50 mL of water, and shake gently, if necessary, to disintegrate the tablet. Do not sonicate. After the tablet has completely disintegrated, add 25 mL of acetonitrile, and shake by mechanical means for 30 minutes. Add 13 mL of 1 N hydrochloric acid, and shake by mechanical means for an additional 5 minutes. Dilute with water to volume, and mix.
pH 2.8 Sodium phosphate solution Dissolve 11.04 g of monobasic sodium phosphate in 950 mL of water. Adjust this solution with phosphoric acid to a pH of 2.8. Transfer the solution to a 1-liter volumetric flask, add water to volume, and mix. Filter through a membrane filter.
Mobile phase Prepare a solution containing 95 volumes of pH 2.8 Sodium phosphate solution and 5 volumes of methanol.
Standard preparation Transfer a suitable quantity of USP Methyldopa RS to a 100-mL volumetric flask to obtain a solution having a known concentration of about 1 mg of anhydrous methyldopa per mL. Add an accurately weighed quantity of USP Hydrochlorothiazide RS that corresponds to the ratio of hydrochlorothiazide to methyldopa in the Tablets. Dissolve in 10 mL of water, 10 mL of acetonitrile, and 5 mL of 1 N hydrochloric acid. Dilute with water to volume, and mix.
Assay preparation Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 250 mg of methyldopa, to a 250-mL volumetric flask, and add 50 mL of water, 25 mL of acetonitrile, and 13 mL of 1 N hydrochloric acid. Shake the flask for 5 minutes, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 270-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate, about 2 mL per minute, is adjusted until the relative retention times for methyldopa and hydrochlorothiazide are about 0.38 and 1.0, respectively. Chromatograph five replicate injections of the Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation is not more than 2.0%, and the resolution factor between methyldopa and hydrochlorothiazide is not less than 6.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph by means of a suitable microsyringe or sampling valve. Record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of methyldopa (C10H13NO4) in the portion of Tablets taken by the formula:
250C(rU / rS)in which C is the concentration, in mg per mL, of USP Methyldopa RS in the Standard preparation; and rU and rS are the responses of the methyldopa peak obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of hydrochlorothiazide (C7H8ClN3O4S2) in the portion of Tablets taken by the same formula, reading hydrochlorothiazide instead of methyldopa.
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USP35NF30 Page 3873