Simultaneous assay of pyrimethamine and methylparaben in extemporaneous pediatric suspensions by an isocratic stability-indicating UPLC-DAD method

Abstract

Pyrimethamine (PYM) is an antiparasitic drug used in the treatment of congenital toxoplasmosis, available only as tablets. Therefore, preparing extemporaneous formulations and their quality control is essential for safe pediatric treatment. This study aimed to develop and validate a stability-indicating method by ultra-performance liquid chromatography (UPLC) to quantify PYM and methylparaben (MP) in extemporaneous oral suspension and evaluate its applicability to the tablets assay. The analytical conditions included RP-C18 column, mobile phase composed of 0.05 M acetate buffer pH 4.5 and organic mixture (acetonitrile:methanol), at 60:40 (v/v), flow rate of 0.2 mL/min, injection volume of 2 µL and detection at 272 nm. PYM was detected at 3.9 min and MP at 4.7 min, without interference of the degradation products or other excipients. Linearity was observed in the range of 0.5 to 25 μg/mL. The method showed accuracy (mean recovery between 98.0 and 102.0%) and precision (RSD < 2%) for suspension and tablets; the method was robust regarding the variations in the analytical conditions. The developed method met the requirements of current guidelines, was indicative of stability, and was suitable for PYM determination in extemporaneous preparations and tablets.

Graphical Abstract

Keywords:

• Chromatography
• methylparaben
• pyrimethamine
• UPLC

Acknowledgments

This study was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brasil) – Finance code 001, and FIT (UFSM). We thank CAPES for their fellowship support to Julya Sarmento Neis and Luana Mota Ferreira and to Prof. Dr. Fernando Fumagalli (UFSM), for the supply of the p-hidroxibenzoic acid standard.

Disclosure statement

The authors declare no conflicts of interest.