A LC-MS/MS METHOD FOR THE DETERMINATION OF LUMEFANTRINE AND ITS METABOLITE DESBUTYL-LUMEFANTRINE IN PLASMA FROM PATIENTS INFECTED WITH PLASMODIUM FALCIPARUM MALARIA

Abstract

& 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 2-2000 ng=mL using 100 lL of plasma. After a simple solvent precipitation procedure, the samples were loaded onto Oasis HLB 1cc (30 mg) extraction columns. Separation was achieved using XTerra RP18 (2.1 mm  100 mm, 5.0 lm) 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 AE9.0%. 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.

Development and validation of a LC–MS/MS method for the quantitation of lumefantrine in mouse whole blood and plasma

“…The developed method uses 20 l of mouse WB or plasma which is the smallest sample volume as compared to other published methods [10][11][12][13][14][15]. The protein precipitation extraction method was robust, efficient and provided high recovery rates for LF in both WB and plasma.…”

“…), ensures that the method is robust and reproducible for analysing samples of unknown concentrations. There are five published LC-MS/MS methods for the quantification of LF in human plasma and one for the quantification of LF in rat plasma [10][11][12][13][14][15]. There seems to be no LC-MS/MS methods for the quantification of LF in mouse WB or plasma.…”

A fast and sensitive method for quantifying lumefantrine and desbutyl-lumefantrine using LC–MS/MS

“…Due to technical limitations including laboriously lengthy extraction process and low sensitivity, earlier high-performance liquid chromatography methods are not adequate for follow up of low LUM levels in small volume samples [126,182,184,185]. Recently, more sensitive liquid chromatography tandem mass spectrometry techniques have been published [186][187][188]. The availability and use of isotope labeled internal standard is preferred in order to overcome matrix effect and ion saturation (interferences leading to signal suppression or enhancement) [188].…”

“…The availability and use of isotope labeled internal standard is preferred in order to overcome matrix effect and ion saturation (interferences leading to signal suppression or enhancement) [188]. Thus, these isotopes are preferred as internal standards rather than structural analogues to LUM like halofantrine [187] in order to improve accuracy and precision of the quantification method [188].…”