A novel approach for LC-MS/MS-based chiral metabolomics fingerprinting and chiral metabolomics extraction using a pair of enantiomers of chiral derivatization reagents

Anal Chim Acta. 2015 Oct 22;898:73-84. doi: 10.1016/j.aca.2015.10.010. Epub 2015 Oct 22.

Abstract

Chiral metabolites are found in a wide variety of living organisms and some of them are understood to be physiologically active compounds and biomarkers. However, the overall analysis of chiral metabolomics is quite difficult due to the high number of metabolites, the significant diversity in their physicochemical properties, and concentration range from metabolite-to-metabolite. To solve this difficulty, we developed a novel approach for chiral metabolomics fingerprinting and chiral metabolomics extraction, which is based on the labeling of a pair of enantiomers of chiral derivatization reagents (i.e., DMT-(S,R)-Pro-OSu and DMT-3(S,R)-Apy) and precursor ion scan chromatography of the derivatives. The multivariate statistics is also required for this strategy. The proposed procedures were evaluated by the detection of a diagnostic marker (i.e., d-lactic acid) using the saliva of diabetic patients. This method was used for the determination of biomarker candidates of chiral amines and carboxyls in Alzheimer's disease (AD) brain homogenates. As the results, l-phenylalanine (L-Phe) and l-lactic acid (L-LA) were identified as the decreased and increased biomarker candidates in the AD brain, respectively. Therefore, the proposed approach seems to be helpful for the determination of non-target chiral metabolomics possessing amines and carboxyls.

Keywords: Alzheimer's disease; Chiral derivatization reagent; Chiral metabolomics; Diabetes mellitus; Reversed-phase chromatography; Tandem mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / analysis
  • Chromatography, Liquid / methods*
  • Indicators and Reagents / chemistry*
  • Metabolomics*
  • Stereoisomerism
  • Tandem Mass Spectrometry / methods*

Substances

  • Amines
  • Indicators and Reagents