Methyldopa and Chlorothiazide Tablets
» Methyldopa and Chlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of methyldopa (C10H13NO4) and chlorothiazide (C7H6ClN3O4S2).
Packaging and storage— Preserve in well-closed containers.
USP Reference standards 11
USP Chlorothiazide RS Click to View Structure
USP Methyldopa RS Click to View Structure
Identification— Transfer the finely ground contents of 1 Tablet to a test tube, add 10 mL of dilute alcohol (1 in 2), shake for 5 minutes, and centrifuge. Use the clear supernatant as the Test solution. Prepare a solution of alcohol and 0.1 N sodium hydroxide (1:1) containing in each mL about 10 mg of USP Methyldopa RS and 10 mg of USP Chlorothiazide RS. Apply 20 µL of the Test solution on a line parallel to and about 2 cm from the bottom edge of a 20-cm × 10-cm thin-layer chromatographic plate (see Chromatography 621) coated with chromatographic silica gel mixture, and apply 20 µL of the Standard solution separately on the starting line. Allow the spots to dry, develop the chromatogram in a solvent system consisting of equal volumes of glacial acetic acid, acetone, butyl alcohol, toluene, and water until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing tank, and allow the solvent to evaporate. View the plate under short-wavelength UV light: the solution under test exhibits two major spots having RF values corresponding to those of the two major spots obtained with the Standard solution.
Dissolution 711
procedure for methyldopa
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 75 rpm.
Time: 30 minutes.
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, and mix. 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, and transfer an aliquot estimated to contain between 2 mg and 3 mg of methyldopa to 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. Pipet 5.0 mL of Ferrous tartrate solution into each flask, dilute with Buffer solution to volume, and mix. Concomitantly determine the absorbances of the treated Standard preparation and test solution 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.
Tolerances— Not less than 80% (Q) of the labeled amount of C10H13NO4 is dissolved in 30 minutes.
procedure for chlorothiazide
Medium: 0.05 M, pH 8.0 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions) containing sodium sulfite (1 in 5000); 900 mL.
Apparatus 2: 75 rpm.
Time: 60 minutes.
Procedure— Determine the amount of C7H6ClN3O4S2 dissolved from UV absorbances of the solution under test, suitably diluted with Medium, if necessary, at the wavelength of maximum absorbance at about 317 nm 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 with respect to methyldopa and to chlorothiazide.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of 0.08 M monobasic sodium phosphate and methanol (95:5). Adjust by the addition of phosphoric acid to a pH of 2.8. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Transfer to a 100-mL volumetric flask accurately weighed quantities of USP Methyldopa RS and USP Chlorothiazide RS, equivalent to one-fifth of their labeled amounts, in mg, per Tablet. Add 15 mL of water and 5 mL of 1 N hydrochloric acid, and sonicate for about 3 minutes. Add 10 mL of acetonitrile, and sonicate for 2 minutes. Dilute with water to volume, and mix.
Assay preparation— Weigh and finely powder not less than 10 Tablets. Transfer an accurately weighed portion of the powder, equivalent to the weight of 1 Tablet, to a 500-mL volumetric flask. Add 75 mL of water and 25 mL of 1 N hydrochloric acid, and sonicate for about 5 minutes. Add 50 mL of acetonitrile, and sonicate for 10 minutes. Dilute with water to volume, and mix. Filter through a 0.45- to 2.0-µm membrane filter, discarding the first 10 mL.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the column efficiency determined from the chlorothiazide peak is not less than 1300 theoretical plates, the tailing factor for chlorothiazide peak is not more than 2, the resolution, R, between the chlorothiazide and methyldopa peaks is not less than 7, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 1.0 for methyldopa and 2.5 for chlorothiazide. Calculate the quantity, in mg, of chlorothiazide (C6H6ClN3O4S2) 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 of the chlorothiazide peak obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of methyldopa (C10H13NO4) taken by the same formula, reading “methyldopa” instead of “chlorothiazide.”
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(GCDF2010) General Chapters - Dosage Forms
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