Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma.
A sensitive and selective method is described for the determination of artemether and its active dihydroartemisinin metabolite in human plasma using artemisinin as internal standard. The method consists of a liquid-liquid extraction with subsequent evaporation of the supernatant to dryness followed by the analysis of the reconstituted sample by liquid chromatography-mass spectrometry (LC-MS) in single ion monitoring mode using atmospheric pressure chemical ionization (APCI) as an interface. Chromatography was performed on a C(18) reversed-phase column using acetonitrile-glacial acetic acid 0.1% (66:34) as a mobile phase. The method was fully validated over a concentration range of 5-200 ng/ml using 0.5 ml of human plasma per assay. Stability assessment was also included. The method was applied to the quantification of artemether and its metabolite in human plasma of healthy volunteers participating in pharmacokinetic drug-drug interaction studies.
Souppart
C
C
Bioanalytics and Pharmacokinetics, Novartis Pharma SA, 2-4 rue Lionel Terray, 92506, Rueil-Malmaison, France. claire.souppart@pharma.novartis.com
Gauducheau
N
N
Sandrenan
N
N
Richard
F
F
D000962:Antimalarials / Q000097:blood* / Q000493:pharmacokinetics; D000077549:Artemether; D037621:Artemisinins; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood* / Q000493:pharmacokinetics
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol; D000077549:Artemether