Pre-analytical Challenges in Clinical Metabolomics: From Bedside to Bench

The field of metabolomics has seen tremendous improvements since its introduction two decades ago, notably with the emergence of highly sensitive and selective analytical instruments and the implementation of sophisticated data analysis procedures. A joint effort among the metabolomics community has fostered the use of standardized protocols, aiming for the generation of high-quality data and increasing confidence in both the identification and quantitation of metabolites in body fluids and tissues. However, an important aspect of the metabolomics workflow that still often remains neglected is the pre-analytical phase, i.e., all the steps occurring between the sample collection at the hospital or study ward and its actual analysis in a laboratory. Indeed, all pre-analytical conditions—from the type of collection tube to the sample handling temperature—can impact the stability of metabolites, potentially leading to inaccurate results. This chapter discusses the pre-analytical considerations relevant to the analysis of blood-based matrices (i.e., whole blood, serum, and plasma) and urine, highlighting the effects of inadequate procedures on the metabolome and lipidome composition. For each step, general practical recommendations are given to help enhance the stability of metabolites through the entire pre-analytical phase and, in turn, the overall quality of the metabolomics data.