Mass Spectrometry : Analytical Aspect

The research work is essentially structured around methodological and analytical developments based on mass spectrometry at the interface of chemistry, biology and physics.

Development of innovative high-throughput and high resolution mass spectrometry metabolomic approaches

In order to meet large-scale health monitoring, it is necessary to have a methodology that can highlight the actual exposure status of the population to chemical risk, in particular the combined long-term and low-dose exposure of several xenobiotics. It is interesting in this perspective to use metabolomic approaches, which consist in highlighting metabolic disruptions thanks to the modifications detected in the analytical fingerprints. However, a metabolomic study involves the spectral analysis of a large number of samples, leading to generally long analysis times. We are seeking to develop expertise in metabolomics (the study of low molecular weight biomarkers), by developing analytical methodologies using very high resolution mass spectrometry to carry out high-throughput metabolomic approaches on different biological matrices. Research work has been carried out for several years in collaboration with INRAE and the CEA-centre de Saclay.

Metabolomics workflow involves three main scientific areas that are biology, analytical chemistry and biology

This was developed using high resolution mass spectrometry instruments such as the FT-ICR-MS and the LTQ-Orbitrap. Very high resolution mass spectrometry is a very promising tool for the direct analysis of metabolites present in a mixture in a complex matrix without prior chromatographic separation.

Such a direct approach has been successfully applied for high-throughput metabolomics studies, as well as for xenometabolome and food metabolome characterization.

Illustration of the structure identification procedure used for a discriminant variable at m/z 273.12694 according to the five-level classification system of Schymanski et *al.* (*Env. Sci. Technol.* 2014, DOI: 10.1021/es5002105). Unambiguous metabolite identification is achieved at level 1 when two spectral data (measured ion mobility values and MS/MS experiments) acquired for the unknown compound and the authentic standard using orthogonal methods are similar.

Coupling of ion mobility and mass spectrometry (IM-MS) for the identification of compounds of biological interest

In this same context, research work is based on the potential of ion mobility for metabolomics and the analysis of various complex mixtures. Ion mobility, providing an additional dimension of separation, makes it possible to increase the selectivity and sensitivity in the characterization of the metabolome, in particular thanks to the ability of this technology to distinguish isomeric compounds. Thus, the analysis of standard metabolites by mobility gave rise to the creation of spectral databases including more than 100 CCS values of about 400 metabolites.

IM-MS has been used for rapid characterization of isomers in biological samples such as estrogen isomers in human urine, but also for profiling of human milk isomeric oligosaccharides (HMOs). More recent research work has focused on the development of a rapid and sensitive method of chiral analysis in the gas phase applied to the field of metabolomics by tandem mass spectrometry and/or ion mobility. Promising IM-MS results allowed the separation of amino acid enantiomers.