An Interlaboratory Comparison of High-Resolution Ion Mobility Collision Cross-Sections from Human Plasma

The increasing adoption of high-resolution ion mobility
(HRIM)
in untargeted omics workflows underscores the need for precise collision
cross-section (CCS) measurements which are highly reproducible across
various laboratories and instrumentation. To evaluate the reproducibility
of a high-resolution ion mobility platform, an interlaboratory study
was undertaken using structures for lossless ion manipulation-based
traveling wave ion mobility spectrometry (TWSLIM) in nitrogen drift
gas. Across 250 lipid features spanning glycerophospholipids, glycerolipids,
and sphingolipids detected from a lipidomic extract of human plasma
standard reference material, the platform demonstrated high CCS measurement
reproducibility, with an average relative standard deviation (%RSD)
of ∼0.1%. Triglycerides in general were found to exhibit multiple
IM features that served as an illustrative example where analysis
via HRIM and data-independent, mobility-aligned fragmentation (MAF)
provides critical insights into their chemical structures. To support
the future development of HRIM in lipidomic workflows, a large (n = 250) number of lipid consensus TWSLIMCCSN2 values was compiled from the interlaboratory study into
a HRIM database for community use.