Abstract

Background: Analytical scientists have constantly been in search for more efficient and economical methods for drug simulation studies. Owing to great progress in this field, there are various techniques available nowadays that mimic drug metabolism in the hepatic microenvironment. The conventional in vitro and in vivo studies pose inherent methodological drawbacks due to which alternative analytical approaches are devised for different drug metabolism experiments.

Methods: Electrochemistry has gained attention due to its benefits over conventional metabolism studies. Because of the protein binding nature of reactive metabolites, it is difficult to identify them directly after formation, although the use of trapping agents aids in their successful identification. Furthermore, various scientific reports confirmed the successful simulation of drug metabolism studies by electrochemical cells. Electrochemical cells coupled with chromatography and mass spectrometry made it easy for direct detection of reactive metabolites. In this review, an insight into the application of electrochemical techniques for metabolism simulation studies has been provided. The sole use of electrochemical cells, as well as their setups on coupling to liquid chromatography and mass spectrometry has been discussed. The importance of metabolism prediction in early drug discovery and development stages along with a brief overview of other conventional methods has also been highlighted.

Conclusion: To the best of our knowledge, this is the first article to review the electrochemistry based strategy for the analysis of reactive metabolites. The outcome of this ‘first of its kind’ review will significantly help the researchers in the application of electrochemistry based bioanalysis for metabolite detection.

Keywords: Bioactivation, conventional techniques, electrochemical analysis, mass spectrometry, reactive metabolite generation, reactive metabolite.

Graphical Abstract