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

•A UHPSFC-MS/MS-based pseudotargeted lipidomics method was established.•The method was applied to a lipidomics study of liquiritin on depression.•Fast speed, high resolution, sensitivity, and repeatability were obtained.•This method had advantages in the separation of lipid isomers.•Up to 758 lipids were quantified and 10 potential biomarkers were identified. The pseudotargeted lipidomics method integrates the advantages of untargeted andtargeted lipidomics methods as a novel emerging approach. In this study, a green andefficient pseudotargeted lipidomics method based on ultra-high performancesupercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) wasdeveloped. The tandem mass spectra of the analytes were obtained by using UHPSFCwith 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 (QqQ MS) in the scheduled MRM mode. In total, 758 potential lipidscorresponding to 509 and 249 MRM transitions were detected within 8 min in positiveand negative modes, respectively. The established pseudotargeted lipidomics methodwas validated to have excellent analytical characteristics. Compared with thepseudotargeted 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 improvedthe 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 investigatingthe lipid profiles of the plasma from the depressed rats and 33 differential variableswere screened, which related to three metabolic pathways. The results indicated thatthe UHPSFC-MS/MS-based pseudotargeted method is reliable and efficient and couldbe used in the lipidomics studies.