Deep-lipidotyping by mass spectrometry: recent technical advances and applications

In-depth structural characterization of lipids is an essential component of lipidomics. There has been a rapid expansion of mass spectrometry methods that are capable of resolving lipid isomers at various structural levels over the past decade. These developments finally make deep-lipidotyping possible, which provides new means to study lipid metabolism and discover new lipid biomarkers. In this review, we discuss recent advancements in tandem mass spectrometry (MS/MS) methods for identification of complex lipids beyond the species (known headgroup information) and molecular species (known chain composition) levels. These include identification at the levels of carbon-carbon double bond (C=C) location and sn-position, as well as characterization of acyl chain modifications. We also discuss the integration of isomer-resolving MS/MS methods with different lipid analysis workflows and their applications in lipidomics. The results showcase the distinct capabilities of deep-lipidotyping in untangling the metabolism of individual isomers and sensitive phenotyping by using relative fractional quantitation of the isomers.

This review discuss recent advancements in tandem mass spectrometry (MS/MS) methods for identification of complex lipids at the levels of carbon-carbon double bond (C=C) location and sn-position, as well as characterization of acyl chain modifications. The integration of isomer-resolving MS/MS methods with different lipid analysis workflows and their applications in lipidomics are also discussed. Specifically, this review covers the following contents: 1) Gas-phase ion activation methods for locating C=C, 2) C=C specific derivatization coupled with MS/MS, 3) Applications of detailed lipid structural analysis; 4) Conclusions and outlook.