Collision Cross-Section Calibration Strategy for Lipid Measurements in SLIM-Based High-Resolution Ion Mobility

• Published in: Journal of the American Society for Mass Spectrometry 2022-07, Vol.33 (7), p.1229-1237
• Main Authors: Rose, Bailey S., May, Jody C., Reardon, Allison R., McLean, John A.
• Format: Article
• Language: English
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1021/jasms.2c00067

Structures for lossless ion manipulation-based high-resolution ion mobility (HRIM) interfaced with mass spectrometry has emerged as a powerful tool for the separation and analysis of many isomeric systems. IM-derived collision cross section (CCS) is increasingly used as a molecular descriptor for structural analysis and feature annotation, but there are few studies on the calibration of CCS from HRIM measurements. Here, we examine the accuracy, reproducibility, and practical applicability of CCS calibration strategies for a broad range of lipid subclasses and develop a straightforward and generalizable framework for obtaining high-resolution CCS values. We explore the utility of using structurally similar custom calibrant sets as well as lipid subclass-specific empirically derived correction factors. While the lipid calibrant sets lowered overall bias of reference CCS values from ∼2–3% to ∼0.5%, application of the subclass-specific correction to values calibrated with a broadly available general calibrant set resulted in biases