Review: Deep lipidomic profiling enabled by the Paternò-Büchi reaction - Pinpointing CC locations and beyond

In recent years, there has been growing interest in the development of advanced lipidomic techniques capable of resolving lipid isomers. The Paternò-Büchi (PB) reaction, coupled with tandem mass spectrometry (MS/MS), has emerged as a powerful tool for analysis of unsaturated lipids.

This review introduces basic principles of PB-MS/MS for identification and quantitation of CC location isomers of lipids and its utilization in determining sn-position and the geometry of CC. Then, the approaches for integrating PB-MS/MS into lipidomic workflows are discussed, including shotgun analysis, direct analysis, online and offline coupling with liquid chromatography-MS, single-cell analysis, and mass spectrometry imaging. Examples are provided to illustrate how deep profiling enabled by PB-MS/MS offers crucial insights into lipid metabolism at the isomer level and facilitates lipidomic phenotyping of diseased tissues and single cells. Finally, the challenges and future directions for the advancement of PB-MS/MS are discussed.

This review summarizes recent advancements in PB-MS/MS, an important tool for structural lipidomics, with a focus on aiding researchers in selecting an appropriate strategy for their specific applications in both fundamental and translational research.