Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application to Evaluation of Fixed-Dose Tablets

摘要

>We developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify the antimalarials artesunate (ARS) and mefloquine (MFQ) in fixed-dose tablets. The detection was performed by a triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) in positive ion mode via electrospray ionization. Chromatographic separation was achieved with an XBridge C18 column (50 ?— 2.1 mm, 5 μm), using isocratic elution (350 μL min-1) of water/acetonitrile/methanol (30:35:35, v/v/v) containing 0.1% formic acid. The method was validated according to the International Conference of Harmonization (ICH) guidelines. The calibration curves obtained for ARS (400 to 600 ng mL-1) and MFQ (800 to 1200 ng mL-1) showed good linearity (r2 0.99), precision (relative standard deviation (RSD): ARS 2.0%; MFQ 1.9%), and accuracy (recoveries: ARS, 102.4-103.4%; MFQ, 97.4-101.6%), and were stable for 24 h at 8 ?oC. The method was successfully applied to commercial tablets, and recoveries of 98.7 ?± 4.7% (ARS) and 105.6 ?± 3.13% (MFQ). The method developed is a reliable alternative for public quality inspection control with the advantage of tandem mass specificity and speed.