Orbitrap Collision Cross Section Measurements Enhance Isomer Annotations in Lipidomics

Despite advances in high-resolution mass spectrometry (HRMS), confident lipid annotation remains challenging due to the extensive chemical diversity of the lipidome and the prevalence of isomeric species. Ion mobility collision cross section (CCS) measurements provide structural information that complements HRMS; however, not all HRMS platforms can perform these measurements, necessitating a trade-off among mass resolution, accuracy, and robustness. Here, we introduce a method to infer lipid CCS values directly from liquid chromatography (LC)-Orbitrap MS experiments (Orbi). We show that Orbitrap mass analyzer pressure readings, and therefore CCS values, are influenced by the LC gradient solv