Untargeted Molecular Discovery in Primary Metabolism: Collision Cross Section as a Molecular Descriptor in Ion Mobility-Mass Spectrometry

Anal Chem. 2018 Dec 18;90(24):14484-14492. doi: 10.1021/acs.analchem.8b04322. Epub 2018 Nov 30.

Abstract

In this work, we established a collision cross section (CCS) library of primary metabolites based on analytical standards in the Mass Spectrometry Metabolite Library of Standards (MSMLS) using a commercially available ion mobility-mass spectrometer (IM-MS). From the 554 unique compounds in the MSMLS plate library, we obtained a total of 1246 CCS measurements over a wide range of biochemical classes and adduct types. Resulting data analysis demonstrated that the curated CCS library provides broad molecular coverage of metabolic pathways and highlights intrinsic mass-mobility relationships for specific metabolite superclasses. The separation and characterization of isomeric metabolites were assessed, and all molecular species contained within the plate library, including isomers, were critically evaluated to determine the analytical separation efficiency in both the mass ( m/ z) and mobility (CCS/ΔCCS) dimension required for untargeted metabolomic analyses. To further demonstrate the analytical utility of CCS as an additional molecular descriptor, a well-characterized biological sample of human plasma serum (NIST SRM 1950) was examined by LC-IM-MS and used to provide a detailed isomeric analysis of carbohydrate constituents by ion mobility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carbohydrates / analysis*
  • Carbohydrates / blood
  • Chromatography, High Pressure Liquid
  • Humans
  • Ion Mobility Spectrometry*
  • Isomerism
  • Mass Spectrometry
  • Metabolomics / methods*

Substances

  • Carbohydrates