Electroanalytical Methods as Tools for Predictive Drug Metabolism Studies

Abstract

The search for new in vitro screening tools for early metabolite profiling and identification is becoming a major focus of interest in the pharmaceutical industry. This is motivated by the hope to avoid late failure in drug development and ultimately to launch safer drugs with fewer side effects. Electroanalytical methods alone or coupled on-line with mass spectrometry, can find a niche in this context as they may be readily implemented for the electrically driven synthesis and characterization of xenobiotics oxidized or reduced form(s). Intimately integrated in a dual electrode-enzyme configuration, electroanalysis offers also a mean to study electron transfer at the redox active center of the enzyme in the presence of a substrate and/or an inhibitor.

Voltammetric Behaviour of Drug Molecules as a Predictor of Metabolic Liabilities

“…However, redox biotransformations are not always a detoxification process [3]. Oxidation is the primary mechanism of reactive electrophilic metabolite formation, and these in turn react with nucleophiles such as DNA or proteins by forming irreversible covalent bonds, which leads to adverse reactions [4]. These redox events can be measured by voltammetric techniques [5].…”

“…EC is an alternative method to study drug metabolism and toxicities in early phases by mimicking phase I metabolism [7][8][9][10]. Crucially, most marketed drugs (including pro-drugs) show electroactivity at solid electrodes [4,11].…”