A LC-MS/MS method for the determination of lumefantrine and its metabolite desbutyl-lumefantrine in plasma from patients infected with Plasmodium falciparum malaria

摘要

A sensitive, specific, and rapid liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of lumefantrine (LF) and its metabolite desbutyl-lumefantrine (DLF) was developed and validated over a concentration range of 2-2000ng/mL using 100μL of plasma. After a simple solvent precipitation procedure, the samples were loaded onto Oasis HLB 1cc (30mg) extraction columns. Separation was achieved using XTerra RP18 (2.1mm×100mm, 5.0m) column with a binary gradient solvent system consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Mass detection was performed using a triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The elution of LF (530.2→512.4), DLF (472.3→454.2) and HF (500.3→142.2) was monitored using multiple reaction monitoring. The extraction recovery of LF, DLF, and HF from human plasma was higher than 85%. The intra- and inter-day precision of LF, DLF, and HF were within 8.0% and the accuracy within ±9.0%. The method was applied to the determination of the concentrations of LF and DLF in patients infected with Plasmodium falciparum malaria on day 3 and 7 after treatment with Lumether.