School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
A method to perform nanoscale automated CYP450-based drug metabolism studies using a capillary as a reaction vessel is described. In-capillary assays consumed only approximately 30 nL of recombinant human CYP450 solution. Ultrafast analysis of substrates and metabolites was achieved off-line by ultrahigh-pressure liquid chromatography coupled to mass spectrometry. This approach was successfully applied to qualitative metabolism studies of six major CYP450 isozymes and CYP2D6 inhibition experiments.