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Targeted metabolomics of CSF in healthy individuals and patients with secondary progressive multiple sclerosis using high-resolution mass spectrometry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0002-6748-6119
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0001-9382-3273
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0002-4137-5517
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2020 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 16, no 2, article id 26Article in journal (Refereed) Published
Abstract [en]

Introduction: Standardized commercial kits enable targeted metabolomics analysis and may thus provide an attractive complement to the more explorative approaches. The kits are typically developed for triple quadrupole mass spectrometers using serum and plasma.

Objectives: Here we measure the concentrations of preselected metabolites in cerebrospinal fluid (CSF) using a kit developed for high-resolution mass spectrometry (HRMS). Secondarily, the study aimed to investigate metabolite alterations in patients with secondary progressive multiple sclerosis (SPMS) compared to controls.

Methods: We performed targeted metabolomics in human CSF on twelve SPMS patients and twelve age and sex-matched healthy controls using the Absolute IDQ-p400 kit (Biocrates Life Sciences AG) developed for HRMS. The extracts were analysed using two methods; liquid chromatography-mass spectrometry (LC-HRMS) and flow injection analysis-MS (FIA-HRMS).

Results: Out of 408 targeted metabolites, 196 (48%) were detected above limit of detection and 35 were absolutely quantified. Metabolites analyzed using LC-HRMS had a median coefficient of variation (CV) of 3% and 2.5% between reinjections the same day and after prolonged storage, respectively. The corresponding results for the FIA-HRMS were a median CV of 27% and 21%, respectively. We found significantly (p < 0.05) elevated levels of glycine, asymmetric dimethylarginine (ADMA), glycerophospholipid PC-O (34:0) and sum of hexoses in SPMS patients compared to controls.

Conclusion: The Absolute IDQ-p400 kit could successfully be used for quantifying targeted metabolites in the CSF. Metabolites quantified using LC-HRMS showed superior reproducibility compared to FIA-HRMS.

Place, publisher, year, edition, pages
SPRINGER , 2020. Vol. 16, no 2, article id 26
Keywords [en]
Cerebrospinal fluid, Targeted metabolomics, Flow injection analysis, High-resolution mass spectrometry, Secondary progressive multiple sclerosis
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-407495DOI: 10.1007/s11306-020-1648-5ISI: 000514900100002PubMedID: 32052189OAI: oai:DiVA.org:uu-407495DiVA, id: diva2:1417151
Funder
Åke Wiberg FoundationAvailable from: 2020-03-26 Created: 2020-03-26 Last updated: 2020-03-26Bibliographically approved

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Carlsson, HenrikAbujrais, SandyHerman, StephanieEmami Khoonsari, PayamÅkerfeldt, TorbjörnBurman, JoachimKultima, Kim

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3334353637383936 of 459
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