Among areas revolutionized by metabolomics in the last decade, those having traits to public health in connection with the chemical safety of food are not outdone (1, 2). When dealing with the investigation of biomarkers of exposure/effect in relation with food producing animals exposure to chemical, although urine, feces and serum are fully relevant matrices at the farm level, tissue samples (muscle, liver, kidney...) offer the advantage over biofluids to investigate the food item itself. This is of prime importance for instance in the case of importation at the border. Although the objective of the metabolomics strategies applied to these various matrices is the same, the nature of the matrix needs to be specifically and carefully considered in order to provide relevant extracts to be characterized. With such matrices dedicated process, the whole metabolome coverage is also greatly improved thanks to the wider and better coverage of the metabolic diversity gained trough matrices dedicated extraction process. In this work, criteria for sample preparation will be developed according to the type of analysis expected (untargeted or targeted) in LC-HRMS. Some generalities on steps of sample preparation will be developed. Matrices analyzed by the platform will be presented explaining the specificities of preparations according to the matrix (feces, tissue ...). These points will be discussed in order to guarantee the quality of the samples and to limit the confounding factors. (1) C. Le Boucher et al., Food Chemistry (2013) 1032–1040 (2) T. Peng et al., Metabolomics (2017) 13:77