Determination of Dihydroqinghaosu in Blood by Pyrolysis Gas Chromatography/Mass Spectrometry

摘要

A sensitive and specific method using packed or capillary column gas chromatography/mass spectrometry (GC/MS) has been developed for the quantitation of the major active metabolite dihydroqinghaosu (DQHS) of the antimalarial drug artesunic acid in blood. Quantification is achieved with an internal standard method, petroleum ether or n-butyl chloride extraction of blood and gas chromatography/mass spectrometry analysis of the extract with selected ion monitoring. Since DQHS is thermally unstable, the method is based on the observations that at high injector temperature and specific GC conditions, DQHS is pyrolyzed to (2S, 3R, 6R)-2-(3-oxobutyl)-3-methyl-6-(R)-2-propanalcyclohexanone. Quantitation of this cyclohexanone pyrolysis product by GC/MS with selected ion monitoring precisely and accurately reflects DQHS blood levels and calibration curves are linear in the range of 10-1000 ng/mL. The method is currently being used for pharmacokinetic and metabolism studies in animals. Reprints. (AW)