title: Ion mobility-derived collision cross section as an additional measure for lipid fingerprinting and identification.
abstract: Despite recent advances in analytical and computational chemistry, lipid identification remains a significant challenge in lipidomics. Ion-mobility spectrometry provides an accurate measure of the molecules' rotationally averaged collision cross-section (CCS) in the gas phase and is thus related to ionic shape. Here, we investigate the use of CCS as a highly specific molecular descriptor for identifying lipids in biological samples. Using traveling wave ion mobility mass spectrometry (MS), we measured the CCS values of over 200 lipids within multiple chemical classes. CCS values derived from ion mobility were not affected by instrument settings or chromatographic conditions, and they were highly reproducible on instruments located in independent laboratories (interlaboratory RSD < 3% for 98% of molecules). CCS values were used as additional molecular descriptors to identify brain lipids using a variety of traditional lipidomic approaches. The addition of CCS improved the reproducibility of analysis in a liquid chromatography-MS workflow and maximized the separation of isobaric species and the signal-to-noise ratio in direct-MS analyses (e.g., "shotgun" lipidomics and MS imaging). These results indicate that adding CCS to databases and lipidomics workflows increases the specificity and selectivity of analysis, thus improving the confidence in lipid identification compared to traditional analytical approaches. The CCS/accurate-mass database described here is made publicly available.
authors.affiliation: Istituto Zooprofilattico Sperimentale della Puglia e Della Basilicata , Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglia
authors.forename: Peggi
authors.initials: P
authors.lastname: Angel
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Williams
authors.forename: Keith
authors.initials: K
authors.lastname: Richardson
authors.forename: Hernando J
authors.initials: HJ
authors.lastname: Olivos
authors.forename: J Will
authors.initials: JW
authors.lastname: Thompson
authors.forename: Lochana
authors.initials: L
authors.lastname: Menikarachchi
authors.forename: Steven
authors.initials: S
authors.lastname: Lai
authors.forename: Callee
authors.initials: C
authors.lastname: Walsh
authors.forename: Arthur
authors.initials: A
authors.lastname: Moseley
authors.forename: Robert S
authors.initials: RS
authors.lastname: Plumb
authors.forename: David F
authors.initials: DF
authors.lastname: Grant
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
authors.forename: James
authors.initials: J
authors.lastname: Langridge
authors.forename: Scott
authors.initials: S
authors.lastname: Geromanos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D008055:Lipids / Q000032:analysis*; D059629:Signal-To-Noise Ratio; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
chemical_list: D008055:Lipids