Metabolic Profiling and Quantitative Analysis of Cerebrospinal Fluid Using Gas Chromatography–Mass Spectrometry: Current Methods and Future Perspectives

Abstract

Cerebrospinal fluid is a key biological fluid for the investigation of new potential biomarkers of central nervous system diseases. Gas chromatography coupled to mass-selective detectors can be used for this investigation at the stages of metabolic profiling and method development. Different sample preparation conditions, including extraction and derivatization, can be applied for the analysis of the most of low-molecular-weight compounds of the cerebrospinal fluid, including metabolites of tryptophan, arachidonic acid, glucose; amino, polyunsaturated fatty and other organic acids; neuroactive steroids; drugs; and toxic metabolites. The literature data analysis revealed the absence of fully validated methods for cerebrospinal fluid analysis, and it presents opportunities for scientists to develop and validate analytical protocols using modern sample preparation techniques, such as microextraction by packed sorbent, dispersive liquid–liquid microextraction, and other potentially applicable techniques.

Pocket-Size Wireless Nanoelectrospray Ionization Mass Spectrometry for Metabolic Analysis of Salty Biofluids and Single Cells

“…Careful analysis of CSF may offer biochemical insights into central nervous system disorders . However, limited-volume CSF could be obtained by lumbar puncture, and only very limited samples (typically <1 mL) are available for scientific purposes after multiple clinical tests . At the same time, comparable concentrations of salts were found in CSF like that in blood, which may cause difficulties for MS analysis.…”

“…8 However, limited-volume CSF could be obtained by lumbar puncture, and only very limited samples (typically <1 mL) are available for scientific purposes after multiple clinical tests. 7 At the same time, comparable concentrations of salts were found in CSF like that in blood, 33 which may cause difficulties for MS analysis. Besides, CSF should be tested after collection as soon as possible to avoid decomposition (Figure S12).…”

“…Besides, nanoESI also shows better sample economy, longer analysis time, high versatility, and wide applicability . Notwithstanding these advantages, the challenges still remain in this realm for the analysis of real biological samples, such as single cells , and human cerebrospinal fluid (CSF). , The analysis of these samples may enhance our understanding of physiological processes at the molecular level. Nevertheless, this can be a challenging task due to the complicated matrix of the sample and the limited volume of the sample.…”

“…On the other hand, rare samples such as human CSF are typically perishable and thus require rapid and timely detection . Point-of-care (POC) testing or fieldable detection facilitates the detection of fresh samples in time. − To develop a POC testing method, whether the sensitivity, robustness, miniaturization, sample economy, ease of operation, and cost of the proposed method meet the poor condition of POC should be taken into consideration.…”

Recent Applications of Gas Chromatography in Bioanalysis

“…This method generated limits of detection (LOD) situated in the range of 0.3-17 ng/ mL [40]. A version of this derivatization reaction, assisted by microwave, was used for the determination of the concentrations of L-amino acids in cerebrospinal fluid in order to have a biochemical insight into central nervous system disorders [41]. A review on this topic has been very recently published and offers information on new potential biomarkers of central nervous system diseases investigated by GC-MS [42].…”