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 (C1/4C) 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.

Automated summary

In-depth structural characterization of lipids is crucial for lipidomics. Advances in mass spectrometry methods have allowed the resolution of lipid isomers at different structural levels, enabling the study of lipid metabolism and discovery of new biomarkers. This review focuses on recent developments in tandem mass spectrometry methods for identifying complex lipids beyond known headgroup and chain composition levels. The integration of isomer-resolving MS/MS methods with different lipid analysis workflows and their applications in lipidomics are also discussed.