作者: Cynthia M. Chavez-Eng , Ryan W. Lutz , Dina Goykhman , Kevin P. Bateman
DOI: 10.1016/J.XPHS.2018.02.023
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摘要: Abstract Methodology for analysis of a microdosing drug cocktail designed to evaluate the contribution drug transporters and metabolizing enzymes disposition was developed using liquid chromatography–mass spectrometry–based detection. Fast sensitive methods were qualified quantification statins (pitavastatin, pitavastain lactone, rosuvastatin, atorvastatin, 2-hydroxy, 4-hydroxy atorvastatin), midazolam, dabigatran in human plasma. Chromatographic separation accomplished reversed-phase chromatography or hydrophilic interaction with gradient elution detection by tandem mass spectrometry positive ionization mode electrospray ionization. The lower limit quantitation (LLOQ) assay 1 pg/mL 6 analytes linear range from 1000 processing 250 μL plasma sample. midazolam LLOQ 0.5 pg/mL. For assay, 10 5000 100 intraday interday precision accuracy assays within acceptable ranges, successfully applied support study where microdose was dosed healthy subjects simultaneous assessment clinical drug-drug interactions mediated major transporters CYP3A.