ArticleAnalytical and bioanalytical chemistry2022
In-line formation and identification of toxic reductive metabolites of aristolochic acid using electrochemistry mass spectrometry coupling.
Article in Analytical and bioanalytical chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors at 2 institutions in 3 countries.
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Abstract
Small-molecule metabolism has been extensively studied in the past decades, notably driven by the development of new pharmaceutical ingredients. The understanding of metabolism is critical to the anticipation of reactive metabolite formation in vivo that is often associated with toxicity. Electrochemistry has been proposed to simulate the oxidoreductive metabolism reaction catalyzed by cytochrome P450, a family of microsomal enzymes strongly involved in xenobiotic metabolism. The implementation of an electrochemical cell online with mass spectrometry allows for the fast formation and identification of the reaction end products. This study discusses the ability of the synthetic electrochemical approach to simulate a complex lactamization reaction that involves the formation of reactive metabolites. Aristolochic acid I was used as a model molecule to evaluate the ability of electrochemical simulation to generate nitroso, hydroxylamine, N-hydroxylactam, lactam, and nitrenium ion metabolites.
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