Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Anal Chem. 2013 Sep 17;85(18):8715-21. doi: 10.1021/ac401712a. Epub 2013 Aug 26.
Recently, the enhanced resolution and sensitivity offered by chemoselective isotope tags have enabled new and enhanced methods for detecting hundreds of quantifiable metabolites in biofluids using nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry. However, the inability to effectively detect the same metabolites using both complementary analytical techniques has hindered the correlation of data derived from the two powerful platforms and thereby the maximization of their combined strengths for applications such as biomarker discovery and the identification of unknown metabolites. With the goal of alleviating this bottleneck, we describe a smart isotope tag, (15)N-cholamine, which possesses two important properties: an NMR sensitive isotope and a permanent charge for MS sensitivity. Using this tag, we demonstrate the detection of carboxyl group containing metabolites in both human serum and urine. By combining the individual strengths of the (15)N label and permanent charge, the smart isotope tag facilitates effective detection of the carboxyl-containing metabolome by both analytical methods. This study demonstrates a unique approach to exploit the combined strength of MS and NMR in the field of metabolomics.
最近，化学选择性同位素标记所提供的增强分辨率和灵敏度使人们能够使用核磁共振（NMR）光谱或质谱法检测生物流体中数百种可定量代谢物的新方法和增强方法。然而，由于无法使用两种互补的分析技术有效地检测到相同的代谢物，这阻碍了两个强大平台的数据相关性，从而无法最大限度地发挥它们在生物标志物发现和未知代谢物鉴定等应用中的综合优势。为了缓解这一瓶颈，我们描述了一种智能同位素标记物（15）N-胆胺，它具有两个重要性质：NMR 敏感同位素和 MS 灵敏度的永久电荷。使用该标签，我们证明了在人血清和尿液中检测含羧基的代谢物。通过结合（15）N 标记和永久电荷的各自优势，智能同位素标记物通过两种分析方法促进了对含羧基代谢组的有效检测。这项研究展示了一种在代谢组学领域利用 MS 和 NMR 综合优势的独特方法。
