Modern sample preparation approaches for small metabolite elucidation to support biomedical research

The analysis of biological samples of clinical interest has certainly many analytical challenges. Among these, the preparation of samples for the determination of metabolites of interest is of paramount importance to avoid error propagation to the following separation/detection steps, but also to simplify the data elaboration. Sample preparation represents the initial key step for the acquisition of reliable and interpretable information. In this review, we showcase and discuss the most recent sample preparation techniques used for biological samples, limiting to those extracting the small (volatile or volatilizable) metabolites, thus those applications which enable the subsequent GC analysis. Essentially, these include the group of sorbent-based and liquid-based sampling techniques. Dedicated sections devoted to both assisted (i.e., ultrasound, microwave) extraction techniques and chemical derivatizations will also be presented. In the discussion, the importance and recent trends towards the development of green solutions in sample preparation, via automation and miniaturization, are highlighted.