Zheng Xueyun, Aly Noor A, Zhou Yuxuan, Dupuis Kevin T, Bilbao Aivett, Paurus Vanessa L, Orton Daniel J, Wilson Ryan, Payne Samuel H, Smith Richard D, Baker Erin S
Biological Sciences Division , Pacific Northwest National Laboratory , 902 Battelle Blvd, P.O. Box 999, MSIN K8-98 , Richland , WA 99352 , USA . Email:
Chem Sci. 2017 Nov 1;8(11):7724-7736. doi: 10.1039/c7sc03464d. Epub 2017 Sep 28.
The confident identification of metabolites and xenobiotics in biological and environmental studies is an analytical challenge due to their immense dynamic range, vast chemical space and structural diversity. Ion mobility spectrometry (IMS) is widely used for small molecule analyses since it can separate isomeric species and be easily coupled with front end separations and mass spectrometry for multidimensional characterizations. However, to date IMS metabolomic and exposomic studies have been limited by an inadequate number of accurate collision cross section (CCS) values for small molecules, causing features to be detected but not confidently identified. In this work, we utilized drift tube IMS (DTIMS) to directly measure CCS values for over 500 small molecules including primary metabolites, secondary metabolites and xenobiotics. Since DTIMS measurements do not need calibrant ions or calibration like some other IMS techniques, they avoid calibration errors which can cause problems in distinguishing structurally similar molecules. All measurements were performed in triplicate in both positive and negative polarities with nitrogen gas and seven different electric fields, so that relative standard deviations (RSD) could be assessed for each molecule and structural differences studied. The primary metabolites analyzed to date have come from key metabolism pathways such as glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle, while the secondary metabolites consisted of classes such as terpenes and flavonoids, and the xenobiotics represented a range of molecules from antibiotics to polycyclic aromatic hydrocarbons. Different CCS trends were observed for several of the diverse small molecule classes and when urine features were matched to the database, the addition of the IMS dimension greatly reduced the possible number of candidate molecules. This CCS database and structural information are freely available for download at http://panomics.pnnl.gov/metabolites/ with new molecules being added frequently.
在生物和环境研究中，由于代谢物和外源性物质具有巨大的动态范围、广阔的化学空间和结构多样性，因此对它们进行可靠的鉴定是一项分析挑战。离子迁移谱（IMS）广泛用于小分子分析，因为它可以分离同分异构体，并且易于与前端分离和质谱联用进行多维表征。然而，迄今为止，IMS代谢组学和暴露组学研究受到小分子准确碰撞截面（CCS）值数量不足的限制，导致特征能够被检测到，但无法可靠地鉴定。在这项工作中，我们利用漂移管IMS（DTIMS）直接测量了500多种小分子的CCS值，这些小分子包括初级代谢物、次级代谢物和外源性物质。由于DTIMS测量不像其他一些IMS技术那样需要校准离子或校准，因此避免了可能导致区分结构相似分子出现问题的校准误差。所有测量均在氮气和七个不同电场下，以正负极性一式三份进行，以便可以评估每个分子的相对标准偏差（RSD）并研究结构差异。迄今为止分析的初级代谢物来自关键代谢途径，如糖酵解、磷酸戊糖途径和三羧酸循环，而次级代谢物包括萜类和黄酮类等类别，外源性物质则代表了从抗生素到多环芳烃等一系列分子。在几种不同的小分子类别中观察到了不同的CCS趋势，当将尿液特征与数据库匹配时，增加IMS维度大大减少了候选分子的可能数量。这个CCS数据库和结构信息可在http://panomics.pnnl.gov/metabolites/免费下载，并且会经常添加新分子。
