Metabolomics‐based parallel discovery of xenobiotics and induced endogenous metabolic dysregulation in clinical toxicology | doi.page

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Metabolomics‐based parallel discovery of xenobiotics and induced endogenous metabolic dysregulation in clinical toxicology

Biomedical Chromatography2018Vol. 33(2), pp. e4413–e4413

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Chang Chen, Ziquan Fan, Hui Xu, Xiaojie Tan, Mingshe Zhu

Abstract

Intoxication by xenobiotics triggers the perturbation of metabolic fingerprints in biofluids, including the accumulation of xenobiotic compounds and the dysregulation of endogenous metabolites. In this work, an untargeted metabolomics workflow was developed to simultaneously profile both xenobiotic and endogenous metabolites for the identification of the xenobiotic origin and an in-depth understanding of the intoxication mechanism. This workflow was demonstrated in a real-world clinical case. Plasma samples were collected from four intoxicated children and another three healthy children. Untargeted metabolomics analysis was performed using ultraperformance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer (HRMS) with data-independent MSE acquisition. LC-MSE data was processed using an untargeted metabolomics data interpretation workflow, in which the identities of xenobiotics and altered endogenous metabolic features were determined via database searching. Five xenobiotic chemicals and 19 endogenous metabolites were found to be dysregulated. Combined with the clinical evidence, penfluridol was confirmed as the xenobiotic toxin. Furthermore, a mechanistic hypothesis was developed to explain the dysregulation of the four endogenous acyl-carnitines. This workflow can be readily applied to a wide range of clinical toxicology cases, offering a powerful and convenient means of simultaneous discovery of intoxication source and the understanding of intoxication mechanisms.

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Abstract

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