Utility of Screen Printed Electrodes for in Vitro Metabolic Stability Assays: Application to Acetaminophen and its Thioconjugates

Abstract

Screen printed electrodes (SPEs), in addition to their utility in the electrochemical quantification of compounds of pharmacological interest may be used (i) for studying the redox pattern of drug candidates by cyclic voltammetry, (ii) for electrochemical synthesis in microvolumes (microelectrosynthesis) at a selected applied potential with subsequent off-line LC-MS identification of the generated products, and (iii) for monitoring enzymatic reactions in microvolumes of samples. The resulting data are of valuable predictive value for in vitro metabolic stability assays. Acetaminophen (APAP) was used as relevant model drug compound to illustrate potential applications of SPEs in pharmaceutical research. The electrooxidation of APAP was studied, in the absence and presence of endogenous thiols, in microvolume sample by cyclic voltammetry and by microelectrolysis at a carbon based SPE (CSPE) and the generated products were identified off-line by liquid chromatography coupled to mass spectrometry (LC-MS).