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Open AccessArticle

Assessing the Pre-Analytical Stability of Small-Molecule Metabolites in Cerebrospinal Fluid Using Direct-Infusion Metabolomics

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Section Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht University, Lundlaan 6, 3584 EA Utrecht, The Netherlands
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Section Metabolic Diseases, Department of Child Health, University Medical Center Utrecht, Utrecht University, Lundlaan 6, 3584 EA Utrecht, The Netherlands
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Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(10), 236; https://doi.org/10.3390/metabo9100236
Received: 28 August 2019 / Revised: 8 October 2019 / Accepted: 17 October 2019 / Published: 18 October 2019
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data. Three cerebrospinal fluid pools were prepared from surplus samples from the Amsterdam Dementia Cohort biobank. Aliquoted pools were exposed to different storage conditions to assess the temperature and freeze/thaw stability before final storage at −80 °C: storage up to four months at −20 °C and up to one week at either 5–8 °C or 18–22 °C and exposure to up to seven freeze/thaw cycles. Direct-infusion high-resolution mass spectrometry was performed, resulting in the identification of 1852 m/z peaks. To test the storage stability, principal component analyses, repeated measures analysis of variance, Kruskal–Wallis tests, and fold change analyses were performed, all demonstrating that small-molecule metabolites in the cerebrospinal fluid (CSF) are relatively unaffected by 1–3 freeze/thaw cycles, by storage at −20 °C up to two months, by storage at 5–8 °C for up to 72 h, or by storage at 18–22 °C for up to 8 h. This suggests that these differences do not affect the interpretation of potential small-molecule biomarkers in multicenter or historical cohorts and implies that these cohorts are suitable for biomarker studies. View Full-Text
Keywords: biomarker stability; pre-analytical storage conditions; small-molecule metabolites; cerebrospinal fluid; metabolomics; direct-infusion mass spectrometry; DIMS; neurometabolic diagnostics biomarker stability; pre-analytical storage conditions; small-molecule metabolites; cerebrospinal fluid; metabolomics; direct-infusion mass spectrometry; DIMS; neurometabolic diagnostics
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Haijes, H.A.; Willemse, E.A.; Gerrits, J.; van der Flier, W.M.; Teunissen, C.E.; Verhoeven-Duif, N.M.; Jans, J.J. Assessing the Pre-Analytical Stability of Small-Molecule Metabolites in Cerebrospinal Fluid Using Direct-Infusion Metabolomics. Metabolites 2019, 9, 236.

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