title: An improved pseudotargeted metabolomics approach using multiple ion monitoring with time-staggered ion lists based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.
abstract: Pseudotargeted metabolomics is a novel strategy integrating the advantages of both untargeted and targeted methods. The conventional pseudotargeted metabolomics required two MS instruments, i.e., ultra-high performance liquid chromatography/quadrupole-time- of-flight mass spectrometry (UHPLC/Q-TOF MS) and UHPLC/triple quadrupole mass spectrometry (UHPLC/QQQ-MS), which makes method transformation inevitable. Furthermore, the picking of ion pairs from thousands of candidates and the swapping of the data between two instruments are the most labor-intensive steps, which greatly limit its application in metabolomic analysis. In the present study, we proposed an improved pseudotargeted metabolomics method that could be achieved on an UHPLC/Q-TOF/MS instrument operated in the multiple ion monitoring (MIM) mode with time-staggered ion lists (tsMIM). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment and ion fusion, a stepwise ion picking procedure was used to generate the ion lists for subsequent single MIM and tsMIM. The UHPLC/Q-TOF tsMIM MS-based pseudotargeted approach exhibited better repeatability and a wider linear range than the UHPLC/Q-TOF MS-based untargeted metabolomics method. Compared to the single MIM mode, the tsMIM significantly increased the coverage of the metabolites detected. The newly developed method was successfully applied to discover plasma biomarkers for alcohol-induced liver injury in mice, which indicated its practicability and great potential in future metabolomics studies.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao. Electronic address: jbwan@umac.mo.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008103:Liver Cirrhosis / Q000097:blood; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers
keywords: Alcohol-induced liver injury; Multiple ion monitoring; Pseudotargeted metabolomics; Time-staggered ion lists