Simultaneous Determination of Artemether and Its Major Metabolites Dihydroartimisinin in Rat Plasma Using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

In order to study the pharmacokinetics of artemether in rats, artemether and its major metabolites dihydroartimisinin in rat plasma were simultaneously determined by an ultra performance liquid chromatography coupled with quadrupole-obitrap mass spectrometric method with high sensitivity. Artemisinin was used as internal standard. Identification and quantification of artemether and dihydroartimisinin were performed with electrospray ionization under a positive Targeted-MS2 monitoring mode. The monitored transitions were m/z 316.2115/163.1117 (artemether), m/z 302.1958/163.1117 (dihydroartimisinin) and m/z 300.1803/209.1536 (artemisinin). A good linearity was obtained in the range of 2-200 mu g/L (R-2 > 0.9990) with a limit of detection of 0.8 mu g/L and a limit of quantification of 2.0 mu g/L for both artemether and dihydroartimisinin. The recoveries of artemether and dihydroartimisinin were 93.7% - 103.7% and 97.4% - 104.7%, respectively. The RSD was less than 9%. The method is rapid, sensitive, reproducible, and can be applied in pharmacokinetic studies of artemether in rats.