Organic molecules such as pesticides are widely used in French and global agriculture. Although they produce high yields, they are not without consequences for the planet, starting with the health of human beings. For this reason, regulations involving maximum residue limits (MRLs) have been implemented. It is accompanied by monitoring and control plans (PSPC) to ensure compliance with legislation by farmers and intermediates. Nevertheless, recent news alerts us on the fact that no system is perfect and this could be explained by various reasons (misuse, human error, terrorism ...) where the regulations are not respected. It is therefore necessary to increase vigilance through the implementation of PSPC which are as comprehensive as possible in order to avoid any contamination. Currently, to detect pesticides, tandem mass spectrometry on triple quadrupole type devices in MRM mode is conventionally used. The latter is generally coupled to liquid chromatography (LC-MS/MS). This technology is recognized as the benchmark for pesticide analysis thanks of its specificity and sensitivity. However, this technique is restricted to a pre-established list of substances to be sought a priori; so-called "targeted" approach. This lack of completeness is a problem because many molecules are likely to be found in the food, so it is important to be able to detect them, the case of Fipronil and the recent contamination of eggs is a perfect one drawing.

Recently, a number of high resolution mass spectrometry (HRMS) devices appeared on the market. These devices allow the detection of a large number of small molecules (<1500 uma) by exploiting the monoisotopic mass of the molecules and generating chemical fingerprints that require the use of bioinformatic tools. This type of approach makes it possible to respond to the lack of comprehensiveness of conventional analyzes through the so-called "untargeted" approaches. Despite the certain advantages of the HRMS on the current approaches implemented in the framework of the PSPC, they have of course their disadvantages. Thus, the four main types of disadvantage that can be mentioned are the sensitivity of the devices to be evaluated, the criteria for identifying contaminants that require the acquisition of MS and MS² spectra, and the impact of the matrix signal (composition, variability) on the generation of a considerable number of features to be examined during the reprocessing of the data and finally the implementation of complex workflows requiring chemometric tools.

At the present time, the LC-HRMS (triple quadrupole coupled to a flight time) is already used in our laboratory but only for qualitative purposes of identification, it relies on a limited number of standards (<100 molecules) and on a reduced number of matrices analyzed each year. In addition, a number of workflows have been successfully implemented on various occasions (European exercises in laboratory performance assessment, research). Despite all this, many challenges remain.

Thus, through this research project we would like to go further and fill in the "gaps" mentioned above. We propose to develop an analytical method on LC-HRMS based on the exhaustive character that the HRMS allows and to add quantification to the latter on a pool of pesticides as wide as possible (> 500 molecules). Once this stage has been reached, it will be essential to carry out the development of the extraction methods necessary for the various food matrices which will be the subject of the work (fruit, vegetables and meat), we will rely on extraction methods "Quick, Easy, Cheap, Rugged and Safe" (QuEChERS) and "Quick, Polar and Pesticide" (QuPPe) best suited to our goal. Finally, a sampling plan will be drawn up in collaboration with ANSES's Directorate for Risk Assessment (DER). This will be an opportunity to investigate through this sampling plan the possible presence of contaminants not sought by conventional PSPCs.

Ultimately, this work should demonstrate the versatility of the approach and enable these research methods to move to routine methods and thus improve the safety and the health of consumers.