Practical Approach for the Identification and Isomer Elucidation of Biomarkers Detected in a Metabonomic Study for the Discovery of Individuals at Risk for Diabetes by Integrating the Chromatographic
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- 作者：Jing Chen ; Xinjie Zhao ; Jens Fritsche ; Peiyuan Yin ; Philippe Schmitt-Kopplin ; Wenzhao Wang ; Xin Lu ; Hans Ulrich Hä ; ring ; Erwin D. Schleicher ; Rainer Lehmann ; Guowang Xu
- 刊名：Analytical Chemistry
- 出版年：2008
- 出版时间：February 15, 2008
- 年：2008
- 卷：80
- 期：4
- 页码：1280 - 1289
- 全文大小：272K
- 年卷期：v.80,no.4(February 15, 2008)
- ISSN：1520-6882
文摘
Sensitive and high-resolution chromatographic-drivenmetabonomomics studies experienced major growth withthe aid of new analytical technologies and bioinformaticssoftware packages. Hence, data collections by LC-MS anddata analyses by multivariate statistical methods are byfar the most straightforward steps, and the detection ofbiomarker candidates can easily be achieved. However,the unequivocal identification of the detected metabolitecandidates, including isomer elucidation, is still a cruxof current metabonomics studies. Here we present acomprehensive analytical strategy for the elucidation ofthe molecular structure of metabolite biomarkers detectedin a metabonomics study, exemplified analyzing spot urineof a cohort of healthy, insulin sensitive subjects andclinically well characterized prediabetic, insulin resistantindividuals. An integrated approach of LC-MS fingerprinting, multivariate statistic analysis, LC-MSn experiments, micro preparation, FTICR-MS, GC retention index,database search, and generation of an isotope labeledstandard was applied. Overall, we could demonstrate theefficiency of our analytical approach by the unambiguouselucidation of the molecular structure of an isomericbiomarker candidate detected in a complex human biofluid. The proposed strategy is a powerful new analyticaltool, which will allow the definite identification of physiologically important molecules in metabonomics studiesfrom basic biochemistry to clinical biomarker discovery.