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J Biomol Tech. 2010 September; 21(3 Suppl): S40.
PMCID: PMC2918220

Simulating Oxidative Metabolism Using On-Line Electrochemistry/Mass Spectrometry

A. Kraj,1 H.J. Brouwer,1 and J. Purkerson2
1Antec Leyden BV, Zoeterwoude, The Netherlands;
2Antec (USA), Palm Bay, FL, United States



The knowledge of the metabolic pathways and the biotransformation of new drugs are crucial for elucidation of degradation routes of new active compounds, especially in the area of possible toxicity. In vitro studies are based on incubating drug candidates with e.g., liver cells (in microsomes activity of cytochrome P450 is high) and isolating and detecting the metabolic products. With the introduction of an on-line electrochemistry/mass spectrometry system (EC/MS), oxidative metabolism, as usually occurring in the liver cells by the Cytochrome P450 oxidation, can be simulated successfully within seconds and detected by electrospray mass spectrometry. Combining electrochemistry with MS creates a robust platform for oxidative metabolite investigations and helps to overcome many of the laborious tasks by isolating the metabolites form in vivo (urine, plasma, etc.) or in vitro (microsomes) studies. Acetaminophen (paracetamol; APAP; IUPAC: N-(4-hydroxyphenyl) acetamide) was chosen as model drug to investigate oxidative metabolism using the on-line EC/MS System dedicated for single component screening. Electrochemical conversion of the acetaminophen into reactive phase I metabolite (N-acetyl-p-benzoquinoneimine, NAPQI) and the NAPQI – glutathione (GSH) phaseII conjugate was successfully achieved. The data can be presented as 3-D mass voltamogramm, which represents ion abundance versus m/z as a function of EC potential.Mass voltammogram can be recorded automatically to obtain a metabolic fingerprint of the compound of interest in a short time frame. Hyphenation of on-line electrochemistry and electrospray mass spectrometry provides a versatile and user-friendly platform for screening of single target compounds (drugs, xenobiotics, etc.) in phase I and II metabolomics studies.

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