Cerebrospinal fluid (CSF) surrounds the brain and spine and contains small molecules, peptides, proteins, etc., which play a role in an essential role in many physiological processes in the central nervous system (CNS). CSF is considered a privileged reservoir for neurological studies because the content of proteins and metabolites and changes in their concentrations directly reflect the internal environment of the brain: it offers a unique window to search for new biomarkers and improve the early diagnosis of diseases. neurological. 1-3]. However, the complexity of the human brain and neurological disorders represent a major obstacle to the identification of novel neurological biomarkers. A biomarker can be defined as a biochemical, pharmacological or physiological indicator of a specific biological state or a defined biological stage of an organism as represented in its characteristic specific sample. Such an indicator should be measurable and possibly useful for diagnostic and/or prognostic purposes such as predicting disease progression, disease activity and the effectiveness of targeted therapy. The identification of specific biomarkers is essential for the realization of personalized medicine, in terms of better estimation of disease risk, personalized therapies and improvement of disease progression [4]. Access to quality biological samples that must be carefully annotated with clinical, molecular, and collection data is fundamental for biomarker research. In fact, sample collection should be based on well-defined protocols that provide the fundamental standard operating procedures (SOPs) for workflow certification. The National Health and Medical Research Council (NHMRC) has recognized biobanks as essential tools for biomedical research and science. A large biob...... middle of paper ......e has been widely described as being associated with suboptimal sample collection and storage [8, 9]. Several different proteins have been proposed as an indicator of correct sample preservation. Keeping in mind all the literature to date, we review these useful proteins for CSF quality control [10-12]. We propose Direct Assessment of Sample Quality (DASQ) by applying a rapid MALDI-TOF-MS methodology to assess the molecular characteristics of sample degradation and oxidation that have often been correlated to pre-analytical phases. and suboptimal CSF storage. This approach will provide a direct and analytical assessment of the appropriate phases of CSF sample collection and storage. Such analysis will check for the presence of blood contamination (e.g. hemoglobin chains), truncated molecular isoforms (e.g. cystatin C) and oxidized proteins (e.g. transthyretin).) [8, 12, 13].