title: Potential of monitoring isotopologues by quantitative gas chromatography with time-of-flight mass spectrometry for metabolomic assay.
abstract: Because of the extreme complexity of metabolomic samples, the effectiveness of quantitative gas chromatography with time-of-flight mass spectrometry depends substantially on the expansion of the linear dynamic range. Facing the existence of numerous saturated detector signals, a data processing method based on monitoring isotopologues has been developed. The monoisotopic ion kept the high mass spectrometry sensitivity, and the less abundant isotopologue ions extended the linear dynamic range. This alternative method was proved to extend the linear dynamic range to five orders of magnitude successfully and overcome the quantitative problems induced by the ion detector saturation. Finally, to validate the applicability, the method was applied to a metabolomic assay of Alzheimer's disease. Comparing with the traditional monoisotopic method, the use of monitoring isotopologues helped us to discover an additional eight metabolites with significant difference and to conduct a more reliable principal component analysis as well. The results demonstrated that monitoring isotopologues in quantitative gas chromatography with time-of-flight mass spectrometry could improve the authenticity of metabolomic analysis.
authors.affiliation: Center for Chinese Medicine Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.|National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Center for Chinese Medicine Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.affiliation: National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D002849:Chromatography, Gas / Q000379:methods*; D006801:Humans; D007554:Isotopes / Q000032:analysis* / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D025341:Principal Component Analysis; D013997:Time Factors
chemical_list: D007554:Isotopes
keywords: Isotopologue ions; Linear dynamic range; Metabolomics; Signal saturation; Time-of-flight mass spectrometry