Metabolic profiling assays are a common in vitro test used to screen drug discovery candidates for safety and efficacy. Biotransformation of xenobiotics, such as drugs, pesticides, and organophosphate chemical warfare nerve agents (CWNAs) generally leads to their detoxification by oxidation and/or conjugation reactions. However, novel metabolic pathways and potential interactions may produce unacceptable levels of toxicity. The biochemical reactions at the tissue and organism levels induced by CWNAs are very complex. If metabolomic work can identify key metabolites present in a given condition, this information can more adequately describe mechanisms of toxicity and potential biochemical points for developing effective CWNA countermeasures. To that end, we have been examining in vitro the metabolites formed following incubation of liver microsomes with the CWNA VX using a high throughput workflow employing UPLC/QTof MSE. The complimentary analytical methodologies of reversed-phase and hydrophilic interaction chromatography were evaluated for effectiveness in identifying unique metabolites.

Enabling in vitro workflow for rapid identification of unique metabolic biomarkers from chemical warfare agent exposure

243rd National Meeting (2012)

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