Application of a liquid chromatography/tandem mass spectrometry method for the pharmacokinetic study of dihydroartemisinin injectable powder in healthy Chinese subjects

作者:Liu, Yiming; Zeng, Xing*; Deng, Yuanhui; Wang, Lu; Feng, Yi; Yang, Liu; Zhou, Dan
来源:Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2009, 877(5-6): 465-470.
DOI:10.1016/j.jchromb.2008.11.039

摘要

A simple, rapid and accurate liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed and validated for quantification of dihydroartemisinin (DHA) in human plasma. Following a simple single-step liquid-liquid extraction with ethyl acetate, the analyte was separated on a C-18 column by isocratic elution with methanol-water-10mM ammonium acetate (80:10:10, v/v/v), and analyzed by mass spectrometry in the positive ion MRM mode. Good linearity was achieved over a wide range of 1.01-2020 ng/mL. Intra- and inter-day precisions were less than 9.0%, and accuracy ranged from 93.0 to 98.2%. The pharmacokinetics of DHA injectable powder was studied for the first time in healthy Subjects by this method. After single intravenous infusion of DHA injectable powder 40, 80 and 160 mg, the elimination half-life (t(1/2 lambda Z) was 1.69, 1.88 and 1.92 h, respectively; mean C.. and AUC increased in proportion to the doses. The pharmacokinetics of DHA fit the linear dynamic feature over the DHA dose range studied.