To gain further insights into lipid structures and reveal FA C=C (DB) positions, DB geometries, and stereospecific numbering (sn) isomers, specialized derivatization, separation, and/or tandem mass spectrometry methods are required. One of the first lipid structure selective methods, termed OzID, was introduced by Blanksby and co-workers utilizing ozone to cleave DB bonds. OzID has been used to investigate DB positions as well as sn-isomers of lipids. Most recently it was used in a large-scale shotgun MS study to investigate sn-isomer abundances in different cell lines. In this study Michael et al. revealed that sn-isomers compositions can differ between cell lines and they identified very long chain FAs attached to phospholipids. Structure selective fragments are also obtained by ultraviolet photodissociation (UVPD), a method pioneered for lipids by Brodbelt and co-workers. By exciting lipid ions with UV light, DB positions, sn-isomers and cyclopropanation sites are identified. But also other methods that use laser light can yield information about lipid structures. The selection of ions attached to lipids can regularly alter fragmentation pathways facilitating formation of fragments that are indicative for DB or methyl branching sites. Lipid fragmentation can also be influenced by introducing new functional groups into lipids by derivatization methods prior to ionization. Whereas a large number of derivatization strategies have been developed, epoxidation and Paternò-Büchi (PB) workflows are most regularly used. All these methodologies can provide some additional information for the overall lipid structure such as DB position, sn-isomers, or FA modifications. However only electron impact excitation of ions from organics has provided direct evidence that E/Z DB isomers of lipids can be distinguished based on fragment ion abundances. To further improve the annotation capabilities for isomers in lipidomics workflows, IMS and LC have been used in combination with these advanced tandem mass spectrometry methods. For example, OzID has been combined with reversed-phase LC (RPLC) for the analysis of the structural diversity of FAs in human plasma. RPLC was also employed to separate PB mixtures and epoxidized lipids .