Quantification of artemisinin in human plasma using liquid chromatography coupled to tandem mass spectrometry

被引:27
作者
Lindegardh, N. [1 ,2 ]
Tarning, J. [1 ]
Toi, P. V. [3 ]
Hien, T. T. [3 ]
Farrar, J. [3 ]
Singhasivanon, P. [1 ]
White, N. J. [1 ,2 ]
Ashton, M. [4 ]
Day, N. P. J. [1 ,2 ]
机构
[1] Mahidol Univ, Fac Trop Med, Bangkok 10400, Thailand
[2] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England
[3] Hosp Trop Dis, Ho Chi Minh City, Vietnam
[4] Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, Gothenburg, Sweden
基金
英国惠康基金;
关键词
Antimalarial; Artemisinin; High throughput; Liquid chromatography/tandem mass spectrometry (LC/MS/MS); Solid phase extraction (SPE); FALCIPARUM-MALARIA; METABOLITE DIHYDROARTEMISININ; RAT PLASMA; ELECTROCHEMICAL DETECTION; BETA-DIHYDROARTEMISININ; ARTESUNATE-MEFLOQUINE; HEALTHY-SUBJECTS; PHARMACOKINETICS; VALIDATION; ASSAY;
D O I
10.1016/j.jpba.2008.12.014
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A liquid chromatographic tandem mass spectroscopy method for the quantification of artemisinin in human heparinised plasma has been developed and validated. The method uses Oasis HLB (TM) mu-elution solid phase extraction 96-well plates to facilitate a high throughput of 192 samples a day. Artesunate (internal standard) in a plasma-water solution was added to plasma (50 mu L) before solid phase extraction. Artemisinin and its internal standard artesunate were analysed by liquid chromatography and MS/MS detection on a Hypersil Gold C18 (100 mm x 2.1 mm, 5 mu m) column using a mobile phase containing acetonitrile-ammonium acetate 10 mM pH 3.5 (50:50, v/v) at a flow rate of 0.5 mL/min. The method has been validated according to published FDA guidelines and showed excellent performance. The within-day, between-day and total precisions expressed as R.S.D., were lower than 8% at all tested quality control levels including the upper and lower limit of quantification. The limit of detection was 0.257 ng/mL for artemisinin and the calibration range was 1.03-762 ng/mL using 50 mu L plasma. The method was free from matrix effects as demonstrated both graphically and quantitatively. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:768 / 773
页数:6
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