Pyrimethamine Compounded Oral Suspension

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

Pyrimethamine Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of pyrimethamine (C₁₂H₁₃ClN₄).

Prepare Pyrimethamine Compounded Oral Suspension 2 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

Pyrimethamine powder 200 mg

Vehicle: a 1:1 mixture of Methylcellulose 1% Solution, and Syrup, NF, a sufficient quantity to make 100 mL

Calculate the required quantity of each ingredient for the total amount to be prepared. Place Pyrimethamine powder in a suitable mortar. Add 2 mL of the Vehicle, and triturate to make a smooth paste. Add an additional 10 mL of the Vehicle to the paste, and levigate to form a suspension. Add increasing volumes of Vehicle to make a liquid that is pourable. Transfer the contents of the mortar to a calibrated bottle. Add enough of the Vehicle to bring to final volume, and mix well.

2 ASSAY

Procedure

Mobile phase: Acetonitrile and 50 mM anhydrous sodium acetate (40:60). Pass through a PVDF membrane filter of 0.45-µm pore size, and degas.

System suitability solution: 0.20 mg/mL of USP Pyrimethamine RS (previously dried) and 0.10 mg/mL of USP Phenacetin RS (previously dried) in methanol

Standard solution: 0.20 mg/mL of USP Pyrimethamine RS (previously dried) in methanol

Sample solution: Shake thoroughly by hand each bottle of Oral Suspension. Prepare 0.20 mg/mL of pyrimethamine from Oral Suspension in methanol. Sonicate, and mix on a vortex mixer.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Autosampler temperature: 10°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for phenacetin and pyrimethamine are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 6.0 between the pyrimethamine and phenacetin peaks, System suitability solution

Column efficiency: NLT 8000 theoretical plates, System suitability solution

Tailing factor: NMT 1.5, System suitability solution

Relative standard deviation: NMT 2.0% for replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pyrimethamine (C₁₂H₁₃ClN₄) in the portion of Oral Suspension taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

Where:

rᵤ = peak response of pyrimethamine from the Sample solution

rₛ = peak response of pyrimethamine from the Standard solution

Cₛ = concentration of USP Pyrimethamine RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of pyrimethamine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 6.6–7.6

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store in a refrigerator or at controlled room temperature.

Beyond-Use Date: NMT 90 days after the date on which it was compounded, when stored in a refrigerator or at controlled room temperature

Labeling: Label it to indicate that it is to be well shaken before use, protect from light, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Phenacetin RS

USP Pyrimethamine RS