title: Ion mobility derived collision cross sections to support metabolomics applications.
abstract: Metabolomics is a rapidly evolving analytical approach in life and health sciences. The structural elucidation of the metabolites of interest remains a major analytical challenge in the metabolomics workflow. Here, we investigate the use of ion mobility as a tool to aid metabolite identification. Ion mobility allows for the measurement of the rotationally averaged collision cross-section (CCS), which gives information about the ionic shape of a molecule in the gas phase. We measured the CCSs of 125 common metabolites using traveling-wave ion mobility-mass spectrometry (TW-IM-MS). CCS measurements were highly reproducible on instruments located in three independent laboratories (RSD < 5% for 99%). We also determined the reproducibility of CCS measurements in various biological matrixes including urine, plasma, platelets, and red blood cells using ultra performance liquid chromatography (UPLC) coupled with TW-IM-MS. The mean RSD was < 2% for 97% of the CCS values, compared to 80% of retention times. Finally, as proof of concept, we used UPLC-TW-IM-MS to compare the cellular metabolome of epithelial and mesenchymal cells, an in vitro model used to study cancer development. Experimentally determined and computationally derived CCS values were used as orthogonal analytical parameters in combination with retention time and accurate mass information to confirm the identity of key metabolites potentially involved in cancer. Thus, our results indicate that adding CCS data to searchable databases and to routine metabolomics workflows will increase the identification confidence compared to traditional analytical approaches.
authors.affiliation: Center for Systems Biology, University of Iceland , IS 101, Reykjavik, Iceland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglia
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Williams
authors.forename: Lochana
authors.initials: L
authors.lastname: Menikarachchi
authors.forename: J Will
authors.initials: JW
authors.lastname: Thompson
authors.forename: Richard
authors.initials: R
authors.lastname: Tyldesley-Worster
authors.forename: Skarphédinn
authors.initials: S
authors.lastname: Halldórsson
authors.forename: Ottar
authors.initials: O
authors.lastname: Rolfsson
authors.forename: Arthur
authors.initials: A
authors.lastname: Moseley
authors.forename: David
authors.initials: D
authors.lastname: Grant
authors.forename: James
authors.initials: J
authors.lastname: Langridge
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D001774:Blood Chemical Analysis / Q000379:methods; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D062126:Databases, Chemical; D058750:Epithelial-Mesenchymal Transition; D005740:Gases; D006801:Humans; D007477:Ions / Q000737:chemistry*; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D015203:Reproducibility of Results; D016482:Urinalysis / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D005740:Gases; D007477:Ions