期刊
ANALYTICAL CHEMISTRY
卷 84, 期 6, 页码 2868-2874出版社
AMER CHEMICAL SOC
DOI: 10.1021/ac203291d
关键词
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资金
- Ministerio de Ciencia e Innovacion [CTQ 2009-08328]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca
- EU [226756]
- Cefic LRi Innovative Science Award
- Royal Society [2010/R4]
- Medical Research Council [G0801056B] Funding Source: researchfish
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 H-1 NMR spectroscopy as a consequence of direct addition of the chiral cosolvating agent (CSA) beta-cyclodextrin (beta CD). 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.
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