Simultaneous determination of artemether and its major metabolite dihydroartemisinin in plasma by gas chromatography-mass spectrometry-selected ion monitoring

A sensitive, selective, and reproducible GC-MS-SIM method was developed for determination of artemether (ARM) and dihydroartemisinin (DHA) in plasma using artemisinin (ART) as internal standard. Solid phase extraction was performed using C-18 Bond Elut cartridges. The analysis was carried out using a HP-5MS 5% phenylmethylsiloxane capillary column. The recoveries of ARM, DHA and ART were 94.9+/-1.6%, 92.2+/-4.1% and 81.3+/-1.2%, respectively. The limit of quantification in plasma was 5 ng/ml (C.V.less than or equal to 17.4% for ARM and 15.2% for DHA). Calibration curves were linear with R(2)greater than or equal to 0.988. Within day coefficients of variation were 3-10.4% for ARM and7.7-14.5% for DHA. Between day coefficients of variations were 6.5-15.4% and 7.6-14.1% for ARM and:DHA. The method is currently being used for pharmacokinetic studies. Preliminary data on pharmacokinetics showed C-max of 245.2 and 35.6 nglml reached at 2 and 3 h and AUC(0-8h), of 2463.6 and 111.8 ngh/ml for ARM and DHA, respectively. (C) 1999 Elsevier Science B.V. All rights reserved.