title: Multiple reaction monitoring-ion pair finder: a systematic approach to transform nontargeted mode to pseudotargeted mode for metabolomics study based on liquid chromatography-mass spectrometry.
abstract: Pseudotargeted metabolic profiling is a novel strategy combining the advantages of both targeted and untargeted methods. The strategy obtains metabolites and their product ions from quadrupole time-of-flight (Q-TOF) MS by information-dependent acquisition (IDA) and then picks targeted ion pairs and measures them on a triple-quadrupole MS by multiple reaction monitoring (MRM). The picking of ion pairs from thousands of candidates is the most time-consuming step of the pseudotargeted strategy. Herein, a systematic and automated approach and software (MRM-Ion Pair Finder) were developed to acquire characteristic MRM ion pairs by precursor ions alignment, MS(2) spectrum extraction and reduction, characteristic product ion selection, and ion fusion. To test the reliability of the approach, a mixture of 15 metabolite standards was first analyzed; the representative ion pairs were correctly picked out. Then, pooled serum samples were further studied, and the results were confirmed by the manual selection. Finally, a comparison with a commercial peak alignment software was performed, and a good characteristic ion coverage of metabolites was obtained. As a proof of concept, the proposed approach was applied to a metabolomics study of liver cancer; 854 metabolite ion pairs were defined in the positive ion mode from serum. Our approach provides a high throughput method which is reliable to acquire MRM ion pairs for pseudotargeted metabolomics with improved metabolite coverage and facilitate more reliable biomarkers discoveries.
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Dai
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Yin
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Zhongda
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Kong
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Shili
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D015203:Reproducibility of Results; D012984:Software