An Electrochemical\nPipette for the Study of Drug Metabolite

Electrochemistry offers an effective\nmeans of mimicking\nenzymatic\nmetabolic pathways, particularly the oxidative pathways catalyzed\nby the cytochrome P450 superfamily. The electrochemical generation\nand identification of metabolites are time-sensitive, necessitating\nadjustable cell designs for an accurate mechanistic interpretation.\nWe present a thin-layer electrode (TLE) that addresses the needs of\nboth the analytical and synthetic electrochemical generation of drug\nmetabolites. The TLE’s ability to conduct experiments on a\nminute-to-hour time scale allows for detailed observation of reaction\nmechanisms for metabolites not easily identified by traditional methods.\nThe utility of the TLE for drug metabolites was benchmarked for electrochemical\noxidation of acetaminophen, acebutolol, and 2-acetyl-4-butyramidophenol,\nknown to produce quinone imine metabolites, i.e., NAPQI, upon oxidation.\nWhen combined with a microelectrode (μE), the TLE enables probing\nof the concentration profiles for metabolic oxidation of these drugs.\nThe micromole scale and pipette-type structure of the TLE facilitate\ncomprehensive structural elucidation of intermediates and products\nusing chromatographic and spectroscopic techniques.