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

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.