Mass spectrometry for biomarkers, disease mechanisms, and drug development in cerebrospinal fluid metabolomics

The high incidence rate, complexity, and intractability of central nervous system (CNS) diseases drive significant interest in understanding the underlying mechanisms involved in the immune response. Cerebrospinal fluid (CSF) is the key biological fluid for the study of CNS diseases. Mass spectrometry (MS)-based metabolomics investigations benefit from the advantages of high sensitivity, high selectivity, and structural identification, and show the satisfactory capacity in CSF metabolome exploration. This work comprehensively summarized sample preparation and MS techniques for identifying CSF metabolomics, focusing on potential quantification methods. For application purposes, we emphasized the investigation based on CSF metabolomics in neurological disease mechanisms, biomarkers discovery, and drug development. Existing challenges and perspectives are proposed, like integration and sharing of CSF metabolite database, standardization of MS detection protocols and data mutual recognition, and data mining of multi-omics data. This work provides a multidisciplinary information about analytical chemistry, medical science and nanomaterials. • Discuss sampling and sample processes for CSF metabolomics. • Review MS and quantification methods. • Investigate the application of CSF metabolomics in neurological disease mechanisms, biomarkers, and drug discovery. • Propose existing challenges and perspectives of CSF metabolite.