Sulfadoxine and Pyrimethamine Tablets
» Sulfadoxine and Pyrimethamine Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of sulfadoxine (C12H14N4O4S) and not less than 90.0 percent and not more than 110.0 percent of the labeled amount of pyrimethamine (C12H13ClN4).
Packaging and storage Preserve in well-closed, light-resistant containers.
USP Reference standards 11
A: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those of the Standard preparations of sulfadoxine and pyrimethamine, relative to the internal standard, as obtained in the Assay.
B: Vigorously shake 700 mg of finely ground Tablet powder with 50 mL of a 1 in 50 solution of ammonium hydroxide in methanol for 3 minutes, and filter. Separately apply 10 µL each of the test solution, a Standard solution of USP Sulfadoxine RS similarly prepared, containing 10 mg per mL, and a Standard solution of USP Pyrimethamine RS similarly prepared, containing 0.5 mg per mL, to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Dry the spots in a current of warm air, and develop the plate in a solvent system consisting of a mixture of heptane, chloroform, a 1 in 20 solution of methanol in alcohol, and glacial acetic acid (4:4:4:1). Allow the solvent front to move about two-thirds of the length of the plate, remove the plate, dry, and examine under short-wavelength UV light: the RF values of the principal spots from the solution under test correspond to the RF values of the principal spots from the corresponding Standard solutions.
Medium: pH 6.8 phosphate buffer, prepared as directed under Buffer Solutions in the section Reagents, Indicators, and Solutions; 1000 mL.
Apparatus 2: 75 rpm.
Time: 30 minutes.
Procedure Determine the amounts of C12H14N4O4S and C12H13ClN4 dissolved, employing the procedure set forth in the Assay, making any necessary modifications.
Tolerances Not less than 60% (Q) of the labeled amount of each of C12H14N4O4S and C12H13ClN4 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements for Content Uniformity with respect to sulfadoxine and to pyrimethamine.
0.1% Phosphoric acid solution Add 1 mL of phosphoric acid to water, and dilute to 1000 mL.
Mobile phase Prepare a suitable degassed and filtered mixture of 0.1% Phosphoric acid solution and acetonitrile (83:17). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Transfer an accurately weighed quantity of USP Sulfadoxine RS and USP Pyrimethamine RS to a suitable volumetric flask, dissolve first with acetonitrile using about 17% of the final volume, then dilute with 0.1% Phosphoric acid solution to volume, and mix to obtain a solution having a known concentration of about 0.4 mg per mL and 0.02 mg per mL, respectively.
Assay preparation Weigh and finely powder not fewer than 10 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 200 mg of sulfadoxine and 10 mg of pyrimethamine, to a 100-mL volumetric flask. Add about 28 mL of acetonitrile, mix, and sonicate for about 30 minutes. Allow to cool, dilute with 0.1% Phosphoric acid to volume, and mix. Pipet a 5.0-mL portion of this solution into a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this diluted solution through a 0.45-µm PVDF filter, discard the first 5 mL, and use the remaining filtrate.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 230-nm detector and a 2.0-mm × 10-cm column that contains 3-µm packing L11. The flow rate is about 0.3 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between pyrimethamine and sulfadoxine is not less than 8; the tailing factor is not more than 2.0 for the pyrimethamine peak and not more than 1.6 for sulfadoxine; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 5 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 percent, of the label claim, of sulfadoxine (C12H14N4O4S) and pyrimethamine (C12H13ClN4) in the portion of Tablets taken by the formula:
100(CS / CU)(rU / rS)in which 100 is the percent conversion factor; CS is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; CU is the concentration, in mg per mL, of the Assay preparation, based on label claim per Tablet; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4712Pharmacopeial Forum: Volume No. 34(2) Page 301