Analysis and Annotation of Phospholipids by Mass Spectrometry-Based Metabolomics

Phospholipids are essential components of membrane lipid bilayers and serve as precursors of multiple signaling molecules, so alterations in their homeostasis are associated with the pathogenesis of numerous diseases. In this context, the application of mass spectrometry-based metabolomics has demonstrated great potential to comprehensively characterize the human phospholipidome. In this chapter, we describe an untargeted method for the determination of phospholipids and other related metabolites in a variety of biological matrices, including plasma/serum, erythrocytes, and tissues, based on the combination of high-throughput direct mass spectrometry fingerprinting and subsequent profiling by ultra-high-performance reversed-phase liquid chromatography coupled to mass spectrometry. Furthermore, we also review the characteristic fragmentation patterns of phospholipids with the aim of providing simple guidelines for their straightforward annotation.