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Research Article

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

    Warunee Hanpithakpong

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    ,
    Benjamas Kamanikom

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    ,
    Pratap Singhasivanon

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    ,
    Nicholas J White

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK

    ,
    Nicholas PJ Day

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK

    &
    Niklas Lindegardh

    † Author for correspondence:

    Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

    Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK

    Published Online:https://doi.org/10.4155/bio.09.6

    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 µl 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 µl) and is highly suitable for clinical studies where plasma volumes are limited, such as pediatric trials.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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