Thermospray mass spectroscopy/high performance liquid chromatographic identification of the metabolites formed from arteether using a rat liver microsome preparation

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Abstract
Thermospray LC/MS methods with internal standardization were developed for the quantification of the antimalarial arteether and six of its metabolites at the 1–10 μg/ml level in liver microsome preparations without the use of solvent extraction. The thermospray mass spectra of arteether and most of its metabolites exhibited strong [M + NH4]+ and [M – OR]+ peaks arising from the molecular ion adduct and the loss of the alkoxy or hydroxy group of the side chain. In addition to the six metabolites for which authentic reference standards were available, three additional metabolites were detected. The major metabolites of arteether were found to be dihydroartemisinin, deoxydihydroartemisinin, 3-hydroxydeoxydihydroartemisinin, two isomers of hydroxyarteether, and 3-hydroxydeoxyarteether. Deoxyartheether was not found at significant concentrations in the microsome preparation.