Servei de Ressonància Magnètica Nuclear, Facultat de Ciències i Biociències, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
Anal Chem. 2012 Mar 20;84(6):2868-74. doi: 10.1021/ac203291d. Epub 2012 Feb 29.
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 (1)H 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.
分子手性的差异仍然是药物代谢和药代动力学领域的一个重要问题，对于制药行业和监管机构而言，手性是许多内源性代谢物的一个重要特征。我们提出了一种无需任何预处理即可快速、直接区分和鉴定人尿中手性药物对映异构体的方法。以众所周知的抗炎化学物质布洛芬为例，我们证明了布洛芬的对映异构体和其主要代谢物之一的葡萄糖醛酸化羧酸盐衍生物的非对映异构体可以通过（1）H NMR 光谱直接添加手性助溶剂（CSA）β-环糊精（β-CD）来分辨。该方法简单、快速且稳健，涉及的样品处理最少，并且不需要对样品进行衍生化或纯化。此外，该方法应该可以区分内源性手性代谢物的对映体，这在手性代谢物在生物流体中区分哺乳动物和微生物来源方面具有潜在价值。从这些初步发现中，我们提出使用 CSA-NMR 光谱进行更广泛和详细的对映体特异性代谢物分析可能比以前报道的更有意义。
