A green and efficient pseudotargeted lipidomics method for the study of depression based on ultra-high performance supercritical fluid chromatography-tandem mass spectrometry

The pseudotargeted lipidomics method integrates the advantages of untargeted and targeted lipidomics methods as a novel emerging approach. In this study, a green and efficient pseudotargeted lipidomics method based on ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) was developed. The tandem mass spectra of the analytes were obtained by using UHPSFC with quadrupole-time of flight MS (Q-TOF MS) in MS E mode and the multiplereaction monitoring (MRM) transitions of the lipidome were defined. Then, thecandidate MRM transitions were verified by UHPSFC with triple quadrupole massspectrometry (QqQMS) in the scheduled MRM mode. In total, 758 potential lipidscorresponding to 509 and 249 MRM transitions were detected within 8 min in positive and negative modes, respectively. The established pseudotargeted lipidomics method was validated to have excellent analytical characteristics. Compared with the pseudotargeted method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), the UHPSFC-MS/MS-basedpseudotargeted method not only reduced the analytical time by half but also improved the sensitivity and resolution for most analytes, especially had better separation forlipid isomers. Besides, the UHPSFC-MS/MS-based pseudotargeted method showedhigher sensitivity and better repeatability for most analytes than the UHPSFC-MS/MS-based untargeted method. The established method was finally applied to investigating the lipid profiles of the plasma from the depressed rats and 33 differential variables were screened, which related to three metabolic pathways. The results indicated that the UHPSFC-MS/MS-based pseudotargeted method is reliable and efficient and could be used in the lipidomics studies. (C) 2020 Elsevier B.V. All rights reserved.