Electrochemical Simulation of Phase I Metabolism for 21 Drugs Using Four Different Working Electrodes in an Automated Screening Setup with MS Detection

Abstract

Background: Electrochemical conversion of xenobiotics has been shown to mimic human phase I metabolism for a few compounds. Materials & methods: Twenty-one compounds were analyzed with a semiautomated electrochemical setup and mass spectrometry detection. Results: The system was able to mimic some metabolic pathways, such as oxygen gain, dealkylation and deiodination, but many of the expected and known metabolites were not produced. Conclusion: Electrochemical conversion is a useful approach for the preparative synthesis of some types of metabolites, but as a screening method for unknown phase I metabolites, the method is, in our opinion, inferior to incubation with human liver microsomes and in vivo experiments with laboratory animals, for example.

Disclaimer

The contents of this publication are the sole responsibility of the authors and can in no way be taken to reflect the views of the European Commission.

Financial & competing interests disclosure

AJ Pedersen was sponsored by the PhD School of the University of Copenhagen. The authors would like to thank the Swiss Federal Office of Public Health (BAG project 12.009410) for financial support. This publication has been produced with the financial support of the Drug Prevention and Information Programme of the European Union (JUST/2011/DPIP/AG/3597), especially in terms of delivering reference compounds. The University of Bern, Institute of Forensic Medicine, is an associate partner in this EU project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate insti­tutional review board approval or have followed the princi­ples outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investi­gations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank their collaborators (V Auwärter, M Stoertzel, S Kneisel and M Hutter, Institute of Legal Medicine, University Medical Center of Freiburg) for their input on this topic.