A liquid chromatographic-tandem mass spectrometric method for determination of artemether and its metabolite dihydroartemisinin in human plasma

Background: Artemether lumefantrine is the most widely recommended artemisinin-based combination treatment for falciparum malaria. Quantification of artemether and its metabolite dihydroartemisinin in biological matrices has traditionally been difficult, with sensitivity being an issue. Results: A high-throughput bioanalytical method for the analysis of artemether and its metabolite dihydroartemisinin in human plasma using solid-phase extraction in the 96-well plate format and liquid chromatography coupled to positive ion mode tandem mass spectroscopy has been developed and validated according to US FDA guidelines. The method uses 50 mu l plasma and covers the calibration range 1.43-500 ng/ml with a limit of detection at 0.36 ng/ml. Conclusions: The developed liquid chromatography tandem mass spectrometry assay is more sensitive than all previous methods despite using a lower plasma volume (50 mu l) and is highly suitable for clinical studies where plasma volumes are limited, such as pediatric trials.