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

作者：Hanpithakpong W; Kamanikom B; Dondorp A M; Singhasivanon P; White N J; Day N P J; Lindegardh N^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2008, 876(1): 61-68.

DOI：10.1016/j.jchromb.2008.10.018

• Antimalarial
• Artesunate
• Dihydroartemisinin
• High throughput
• Liquid chromatography/tandem mass spectrometry (LC-MS/MS)
• Stable isotope labeled (SIL) internal standard
• Solid phase extraction (SPE)

A bioanalytical method for the analysis of artesunate and its metabolite dihydroartemisinin in human plasma using high throughput solid-phase extraction in the 96-wellplate format and liquid chromatography coupled to positive tandem mass spectroscopy has been developed and validated. The method was validated according to published FDA guidelines and showed excellent performance. The within-clay and between-day precisions expressed as RSD, were lower than 7% at all tested concentrations including the lower limit of quantification. Using 50 mu l plasma the calibration range was 1.19-728 ng/ml with a limit of detection at 0.5 ng/ml for artesunate and 1.96-2500 ng/ml with a limit of detection at 0.6 ng/ml for dihydroartemisinin. Using 250 mu l of plasma sample the lower limit of quantification was decreased to 0.119 ng/ml for artesunate and 0.196 ng/ml dihydroartemisinin. Validation of over-curve samples in plasma ensured that accurate estimation Would be possible with dilution if samples went outside the calibration range. The method was free from matrix effects as demonstrated both graphically and quantitatively.

• 出版日期2008-12-1