A structural examination and collision cross section database for over 500 metabolites and xenobiotics using drift tube ion mobility spectrometry

• Published in: Chemical science (Cambridge) Vol. 8; no. 11
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Royal Society of Chemistry 27.09.2017
• Subjects: BASIC BIOLOGICAL SCIENCES; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
• ISSN: 2041-6520; 2041-6539

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 450 small molecules including primary metabolites, secondary metabolites and xenobiotics. Since DTIMS measurements do not need calibrates, they avoid calibration errors which can cause CCS accuracy problems and difficulties identifying structurally similar molecules. Furthermore, 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 selected for the database are from key metabolism pathways such as glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle, while the secondary metabolites consist of classes such as terpenes and flavonoids, and the xenobiotics represent a range of molecules from antibiotics to polycyclic aromatic hydrocarbons. Different CCS trends were observed for several of the diverse small molecule classes, allowing insight in their separations and a possible why of classifying unknowns. This CCS database and structural information are freely available for download at http://panomics.pnnl.gov/metabolites/ with new molecules being added monthly.