Mass Spectrometry Based on Chemical Derivatization Has Brought Novel Discoveries to Lipidomics: A Comprehensive Review

Lipids, as one of the most important organic compounds in organisms, are important components of cells and participate in energy storage and signal transduction of living organisms. As a rapidly rising field, lipidomics research involves the identification and quantification of multiple classes of lipid molecules, as well as the structure, function, dynamics, and interactions of lipids in living organisms. Due to its inherent high selectivity and high sensitivity, mass spectrometry (MS) is the "gold standard" analysis technique for small molecules in biological samples. The combination chemical derivatization with MS detection is a unique strategy that could improve MS ionization efficiency, facilitate structure identification and quantitative analysis. Herein, this review discusses derivatization-based MS strategies for lipidomic analysis over the past decade and focuses on all the reported lipid categories, including fatty acids and modified fatty acids, glycerolipids, glycerophospholipids, sterols and saccharolipids. The functional groups of lipids mainly involved in chemical derivatization include the C=C group, carboxyl group, hydroxyl group, amino group, carbonyl group. Furthermore, representative applications of these derivatization-based lipid profiling methods were summarized. Finally, challenges and countermeasures of lipid derivatization are mentioned and highlighted to guide future studies of derivatization-based MS strategy in lipidomics.