Chiral Mass Spectrometry Analysis for Metabolomics – CHIRAMICS

The chirality plays a decisive role in life. However, stereochemistry determination remains largely unexplored and extremely challenging in large scale metabolomic studies because of the complexity of biological samples and the structural chemical variety of molecules constituting the metabolome. The objective of the CHIRAMICS project is to develop a methodology for high throughput and sensitive gas phase chiral analysis to be applied in a metabolomic context. In fact, conventional techniques (UV, NMR…) failed to provide selectivity and often lack of sensitivity in complex mixtures. Here, mass spectrometry based methods using tandem mass spectrometry experiments hyphenated with ion mobility spectrometry will be investigated. The key issue is based on chiral recognition through the production of non covalent diastereoisomeric multimer ions displaying specific gas phase behaviors. These chiral metabolome analyzes will be applied for characterization and quantification (relative enantiomeric content) of various classes of chiral metabolites (amino acids, organic acids, amines…). Therefore, two main objectives will concern the ability of the method to solve stereoisomer mixture and its validation for high accuracy calculations of the enantiomeric excess within the mixtures. The optimization of such gas phase chiral methods will allow to determine the relative content of chiral metabolites produced by catalytic and enzymatic asymmetric reactions. Finally, to check the applicability of these chiral methods in large scale metabolomic studies, the relative quantification of some chiral metabolites of interest will be carried out to access the matrix effects in biological fluids.