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3C-O1-M-1000 PDF
High accuracy chiral metabolomics for biomarker discovery in Alzheimer's disease
LC-MS chiral metabolomics studies are challenging because pairs of enantiomers cannot be separated by both conventional LC and MS methods. For the analysis of chiral metabolites, we have previously developed iCAN-Met, a method based on data-dependent MS/MS analysis of LC quadrupole time-of-flight and chiral derivatization to separate the resulting diastereomers resulting from LC. This method allows for a highly accurate comparison of the metabolite profile including chiral species, identifies the metabolite from the m/z in the MS/MS spectra, and allows for the correction of all detected derivatives by parallel derivatization of isotope-coded and non-coded reagents. Thereby, 0.5-2% (D-/L-isomer) variation of isomers can be correctly recognized, and we concluded the iCAN-Met is a useful tool for chiral metabolomics with trace-level variations.
Herein, we report the application of iCAN-Met to the cerebrospinal fluid from patients with Alzheimer’s disease (AD) for biomarker discovery. Metabolic biomarkers that clearly discriminate AD from healthy subjects have rarely been previously reported. Several biomarkers including chiral metabolite candidates were determined, which can potentially be used as novel biomarkers.