An Electrochemical Pipette for the Study of Drug Metabolite

Abstract

Electrochemistry offers an effective means of mimicking enzymatic metabolic pathways, particularly the oxidative pathways catalyzed by the cytochrome P450 superfamily. The electrochemical generation and identification of metabolites are time-sensitive, necessitating adjustable cell designs for an accurate mechanistic interpretation. We present a thin-layer electrode (TLE) that addresses the needs of both the analytical and synthetic electrochemical generation of drug metabolites. The TLE's ability to conduct experiments on a minute-to-hour time scale allows for detailed observation of reaction mechanisms for metabolites not easily identified by traditional methods. The utility of the TLE for drug metabolites was benchmarked for electrochemical oxidation of acetaminophen, acebutolol, and 2-acetyl-4-butyramidophenol, known to produce quinone imine metabolites, i.e., NAPQI, upon oxidation. When combined with a microelectrode (μE), the TLE enables probing of the concentration profiles for metabolic oxidation of these drugs. The micromole scale and pipette-type structure of the TLE facilitate comprehensive structural elucidation of intermediates and products using chromatographic and spectroscopic techniques.