Isotope Labeling Liquid Chromatography Mass Spectrometry: Metabolite Identification and Human Salivary Metabolome Profiling
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Abstract
The objective of this work was to use paired labeling reagents that are chemically identical but isotopically different to provide a simple and robust way of mass spectrometry (MS)-based metabolome profiling. A differential 13C-/12C-isotope dansyl chloride (DnsCl) derivatization strategy has been further developed and applied for qualitative and quantitative profiling of amine- and phenol-containing metabolites by liquid chromatography electrospray ionization Fourier Transform ion cyclotron resonance MS (LC-ESI FT-ICR-MS). For labeled metabolites, a new technique using skimmer-region fragmentation, followed by tandem MS analysis of formed fragment ions, was developed for generating structural information. In addition, a new method based on use of this isotope labeling LC-MS platform was developed for human salivary metabolome analysis. It offered superior performance over other reported methods for saliva metabolome profiling. Its potential utility for disease biomarker discovery was demonstrated in the analysis of metabolomic differences between normal individuals and diseased-individuals with mild cognitive impairment (MCI).