Simultaneous determination of artemether and its major metabolite dihydroartemisinin in plasma by gas chromatography–mass spectrometry-selected ion monitoring |
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Authors: | S S Mohamed S A Khalid S A Ward T S M Wan H P O Tang M Zheng R K Haynes G Edwards |
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Institution: | a Department of Pharmaceutics, Faculty of Pharmacy, P.O. Box 1996, University of Khartoum, Khartoum, Sudan;b Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan;c Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, UK;d Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK;e Department of Chemistry, Hong Kong University of Science and Technology, Clear water Bay, Kowloon, Hong Kong, PR China |
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Abstract: | A sensitive, selective, and reproducible GC–MS–SIM method was developed for determination of artemether (ARM) and dihydroartemisinin (DHA) in plasma using artemisinin (ART) as internal standard. Solid phase extraction was performed using C18 Bond Elut cartridges. The analysis was carried out using a HP-5MS 5% phenylmethylsiloxane capillary column. The recoveries of ARM, DHA and ART were 94.9±1.6%, 92.2±4.1% and 81.3±1.2%, respectively. The limit of quantification in plasma was 5 ng/ml (C.V.≤17.4% for ARM and 15.2% for DHA). Calibration curves were linear with R2≥0.988. Within day coefficients of variation were 3–10.4% for ARM and 7.7–14.5% for DHA. Between day coefficients of variations were 6.5–15.4% and 7.6–14.1% for ARM and DHA. The method is currently being used for pharmacokinetic studies. Preliminary data on pharmacokinetics showed Cmax of 245.2 and 35.6 ng/ml reached at 2 and 3 h and AUC0–8h of 2463.6 and 111.8 ngh/ml for ARM and DHA, respectively. |
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Keywords: | Artemether Dihydroartemisinin |
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