Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 55, Issue 2, Pages 373-378Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2011.01.036
Keywords
Antimalarial; Artemether; DHA; Liquid-liquid extraction; LC/MS/MS; Method development and validation
Categories
Funding
- Medecins Sans Frontieres
- European Commission [Europe Aid/117571/C/G/Multi]
- Irish Department of Foreign Affairs
- ACT Consortium
- Bill and Melinda Gates Foundation
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A solvent extraction method was developed and validated for the determination of the antimalarial drug, artemether and its active metabolite dihydroartemisinin (DNA) in malaria patient plasma samples. An AB Sciex 4000 triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode was used for detection in the positive ionisation mode. Liquid-liquid extraction was followed by PFP liquid chromatography and tandem mass spectrometry. Stable isotope labelled artemether and DHA was used as internal standards. The calibration range was between 2.00 and 500 ng/ml for both artemether and DHA during the original validation and the upper limit was lowered to 200 ng/ml during a re-instatement validation, prior to sample analysis. The assay was used to measure artemether and DHA in human plasma samples, which were generated from a safety and efficacy clinical trial in Mbarara, Uganda: as well as for a pharmacokinetic interaction study between the antimalarial combination artemether/lumefantrine and combination antiretroviral therapy including nevirapine in HIV-infected adults. (C) 2011 Elsevier B.V. All rights reserved.
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