Opportunities and Challenges of the Application of Nuclear Magnetic Resonance‐Based Cerebrospinal Fluid Metabolomics for Clinical Research

Cerebrospinal fluid (CSF) is an important human biofluid studied within neurological implications. The objective of this literature review is to explore the potential of quantitative nuclear magnetic resonance (NMR) spectroscopy for a precise and reproducible measurement of metabolites in CSF. A two‐source‐based literature search is conducted among entries from a Web of Science Core Collection (owned by Clarivate) and the PubMed library, with the objective of researching NMR‐based investigations of human CSF. The query results are then rerouted toward key summaries pertaining to NMR experiments, sample preparation, and identified metabolites. 94 papers focusing on sample preparation and NMR methods and 49 papers that reported about CSF metabolite concentrations with an overall total of 114 different metabolites that can be detected by NMR are identified. The findings are summarized in comprehensive tables to facilitate future research and use of harmonized protocols regarding sample preparation and measurement. While a large set of metabolites can be measured in CSF, many different sample preparation protocols and analytical settings are used. This is a major drawback for the translation of CSF NMR spectroscopy to a clinical setting, so future studies should try to harmonize preanalytical and analytical conditions and apply absolute quantitation.