Optimization of an LC–MS Method for the Determination of Artesunate and Dihydroartemisinin Plasma Levels using Liquid

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Published: Journal of Analytical Toxicology, ISSN 0146-4760, Volume 32, Number 2, March, pp.133-139

Optimization of an LC–MS Method for the Determination of Artesunate and Dihydroartemisinin Plasma Levels using Liquid–Liquid Extraction
Stijn A.A. Van Quekelberghe[1], Shahid A. Soomro[2], Jan A. Cordonnier[1], and F. Herwig Jansen[2]
[1]Chemiphar, L. Bauwensstraat 4, B-8200 Brugge, Belgium and
[2]Dafra Pharma nv, Slachthuisstraat 30, B-2300 Turnhout, Belgium

Artesunate is a derivate of artemisinin, an antimalarial drug used for the treatment of malaria caused by Plasmodium falciparum and related parasites. Artesunate is hydrolyzed rapidly to dihydroartemisinin in vivo. It has been found that artemisinin and its derivatives may have neurotoxic effects. A method was developed to analyze human plasma samples for the contents of artesunate and dihydroartemisinin. The plasma samples are extracted with ethyl acetate, concentrated, and redissolved in water/acetonitrile. Analyses was performed with liquid chromatography–mass spectrometry using a binary gradient program with aquaeous formic acid and acetonitrile formic acid on a XTerra MS C18-column. The mass spectrometer was operated in the positive atmospheric pressure chemical ionization mode with single ion recording. The lower limits of detection were 10 and 25 ng/mL plasma for DHA and artesunate, respectively. The method was validated according to the guidelines for validation of bioanalytical methods.

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