Sulfadoxine and Pyrimethamine Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Sulfadoxine and Pyrimethamine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of sulfadoxine (C₁₂H₁₄N₄O₄S) and NLT 90.0% and NMT 110.0% of the labeled amount of pyrimethamine (C₁₂H₁₃ClN₄).

2 IDENTIFICATION

A. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution for pyrimethamine and sulfadoxine, as obtained in the Assay.

B.

Diluent: Ammonium hydroxide and methanol (1 in 50)

Standard solution A: 10 mg/mL of USP Sulfadoxine RS in Diluent

Standard solution B: 0.5 mg/mL of USP Pyrimethamine RS in Diluent

Sample solution: Vigorously shake 700 mg of finely ground Tablet powder with 50 mL of Diluent for 3 min, and filter.

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 μL

Developing solvent system: Heptane, chloroform, solution of methanol in alcohol (1 in 20), and glacial acetic acid (4:4:4:1)

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

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.

Acceptance criteria: The R values of the principal spots from the Sample solution correspond to the R values of the principal spots from the corresponding Standard solution.

3 ASSAY

Procedure

Solution A: 1 mL of phosphoric acid in 1000 mL of water

Mobile phase: Acetonitrile and Solution A (17:83)

Standard solution: 0.4 mg/mL of USP Sulfadoxine RS and 0.02 mg/mL of USP Pyrimethamine RS prepared as follows. Transfer suitable amounts of USP Sulfadoxine RS and USP Pyrimethamine RS to a suitable volumetric flask. Dissolve in acetonitrile using about 17% of the final flask volume, then dilute with Solution A to volume.

Sample stock solution: Transfer an equivalent of about 200 mg of sulfadoxine and 10 mg of pyrimethamine from NLT 10 finely powdered

Tablets to a 100-mL volumetric flask. Add about 28 mL of acetonitrile and sonicate for about 30 min. Allow to cool and dilute with Solution A to volume.

Sample solution: Nominally 0.4 mg/mL of sulfadoxine and 0.02 mg/mL of pyrimethamine in Mobile phase from Sample stock solution. Pass through a PVDF filter of 0.45-μm pore size. Discard the first 5 mL and use the remaining filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 2.0-mm × 10-cm; 3-μm packing L11

Flow rate: 0.3 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.5 between pyrimethamine and sulfadoxine

Tailing factor: NMT 1.6 for sulfadoxine; NMT 2.0 for pyrimethamine

Relative standard deviation: NMT 2.0% for both sulfadoxine and pyrimethamine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of sulfadoxine (C₁₂H₁₄N₄O₄S) and pyrimethamine (C₁₂H₁₃ClN₄) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of sulfadoxine or pyrimethamine from the Sample solution

r_S = peak response of sulfadoxine or pyrimethamine from the Standard solution

C_S = concentration of USP Sulfadoxine RS or USP Pyrimethamine RS in the Standard solution (mg/mL)

C_U = nominal concentration of sulfadoxine or pyrimethamine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0% each for sulfadoxine and pyrimethamine

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: pH 6.8 Phosphate Buffer, prepared as directed in Reagents, Indicators, and Solutions—Buffer Solutions; 1000 mL

Apparatus 2: 75 rpm

Time: 30 min

Analysis: Determine the percentage of the labeled amounts of sulfadoxine (C₁₂H₁₄N₄O₄S) and pyrimethamine (C₁₂H₁₃ClN₄) dissolved, using the procedure set forth in the Assay, making any necessary modifications.

Tolerances: NLT 60% (Q) of the labeled amounts each of sulfadoxine (C₁₂H₁₄N₄O₄S) and pyrimethamine (CC₁₂H₁₃ClN₄) is dissolved.

Uniformity of Dosage Units 〈905〉, Content Uniformity: Meet the requirements with respect to sulfadoxine and to pyrimethamine

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

USP Reference Standards 〈11〉

USP Pyrimethamine RS

USP Sulfadoxine RS