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Determining Protein Adducts of Fipexide: Mass Spectrometry Based Assay for Confirming the Involvement of Its Reactive Metabolite in Covalent Binding by Lekha Sleno; Emmanuel Varesio; Gérard Hopfgartner is a Chemistry article available to read on EtoBox.

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## Abstract Fipexide is a nootropic drug, withdrawn from the market due to its idiosyncratic drug reactions causing adverse effects in man. Previous work on its metabolites has identified several potential reactive metabolites which could be implicated in protein binding. Here, we investigated the formation of these metabolites in rat and human hepatocytes. Based on these results, the __o__‐quinone of fipexide (FIP), formed via the demethylenation reaction through a catechol intermediate, was chosen for further investigation. Studies were then pursued in order to relate this metabolite to protein binding, and thus better understand potential mechanisms for the toxicity of the parent compound. An assay was developed for determining the fipexide catechol‐cysteine adduct in the microsomal protein fractions following __in vitro__ incubations. This method digests the entire protein fraction into amino acids, followed by the detection of the Cys‐metabolite adduct by liquid chromatography/mass spectrometry (LC/MS). We have designed a strategy where drug metabolism taking place in microsomal incubations and involved in protein binding can be assessed after the proteins have been digested,

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Author

Lekha Sleno; Emmanuel Varesio; Gérard Hopfgartner

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0951-4198)

Published

2007

Language

EN

Field

Chemistry (Physical Sciences)