Chiral metabonomics: 1H NMR-based enantiospecific differentiation of metabolites in human urine via direct cosolvation with β-cyclodextrin

Míriam Pérez-Trujillo, John C. Lindon, Teodor Parella, Hector C. Keun, Jeremy K. Nicholson, Toby J. Athersuch

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    27 Citations (Scopus)

    Abstract

    Differences in molecular chirality remain an important issue in drug metabolism and pharmacokinetics for the pharmaceutical industry and regulatory authorities, and chirality is an important feature of many endogenous metabolites. We present a method for the rapid, direct differentiation and identification of chiral drug enantiomers in human urine without pretreatment of any kind. Using the well-known anti-inflammatory chemical ibuprofen as one example, we demonstrate that the enantiomers of ibuprofen and the diastereoisomers of one of its main metabolites, the glucuronidated carboxylate derivative, can be resolved by 1H NMR spectroscopy as a consequence of direct addition of the chiral cosolvating agent (CSA) β-cyclodextrin (βCD). This approach is simple, rapid, and robust, involves minimal sample manipulation, and does not require derivatization or purification of the sample. In addition, the method should allow the enantiodifferentiation of endogenous chiral metabolites, and this has potential value for differentiating metabolites from mammalian and microbial sources in biofluids. From these initial findings, we propose that more extensive and detailed enantiospecific metabolic profiling could be possible using CSA-NMR spectroscopy than has been previously reported. © 2012 American Chemical Society.
    Original languageEnglish
    Pages (from-to)2868-2874
    JournalAnalytical Chemistry
    Volume84
    Issue number6
    DOIs
    Publication statusPublished - 20 Mar 2012

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