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.

Highlights

  • Modern differential diagnostics of a wide variety of diseases and pathologies is not complete without analyzing the composition of biological fluids of the body

  • 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

  • As noted by the authors, despite the greater number of compounds determined by the nuclear magnetic resonance (NMR), the potential remains with GC–MS when using selective methods of sample preparation and derivatization, as well as when using TOF mass spectrometry

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Summary

Introduction

Modern differential diagnostics of a wide variety of diseases and pathologies is not complete without analyzing the composition of biological fluids of the body. The limited available sample volume requires the use of modern efficient sample preparation techniques and sensitive analytical methods for the determination of metabolites, most often at the trace level. Such methods are chromatographic ones, namely gas (GC) and high-performance liquid chromatography (HPLC) in combination with different mass-selective (MS) detectors (single quadrupole (Q), time-of-flight (TOF), including high resolution equipment and tandem MS/MS or Q-TOF) [22]. Selected sample preparation conditions lead to the quantitative determination of different classes of chemical compounds in one chromatographic analysis, which meets the above requirements. The keywords “cerebrospinal fluid” and “gas chromatography–mass spectrometry” or “GC–MS” were used in combination in the search list

The Human Cerebrospinal Fluid Metabolome
Aim
Method Validation
Amino Acids
Tryptophan Metabolites
Organic Acids
Neuroactive Steroids
Arachidonic Acid Metabolites
Glucose Metabolites
Drugs and Toxic Metabolites
Miniaturization in Sample Preparation Techniques for the GC–MS Analysis
Findings
Conclusions

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