Simultaneous measurement of kynurenine metabolites and explorative metabolomics using liquid chromatography-mass spectrometry: A novel accurate method applied to serum and plasma samples from a large healthy cohort

Kynurenine metabolites are emerging as promising clinical biomarkers in several diseases, especially within psychiatry. Unfortunately, they are difficult to detect, particularly the challenging neurotoxic metabolite quinolinic acid (QUIN). The aim of this study was twofold: First, to develop a liqui...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2023-04, Vol.227, p.115304-115304, Article 115304
Main Authors: Eggertsen, Peter Preben, Hansen, Jakob, Andersen, Malene Lundfold, Nielsen, Jørgen Feldbæk, Olsen, Rikke Katrine Jentoft, Palmfeldt, Johan
Format: Article
Language:English
Subjects:
Biomarker
Chromatography, Liquid - methods
Female
Human blood
Humans
Kynurenic Acid
Kynurenine - metabolism
Kynurenine metabolites
LC-MS
Male
Tandem Mass Spectrometry - methods
Tryptophan - metabolism
Untargeted metabolomics
Young Adult
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Summary:Kynurenine metabolites are emerging as promising clinical biomarkers in several diseases, especially within psychiatry. Unfortunately, they are difficult to detect, particularly the challenging neurotoxic metabolite quinolinic acid (QUIN). The aim of this study was twofold: First, to develop a liquid chromatography-mass spectrometry method (LC-MS) for simultaneous targeted quantification of key kynurenine metabolites together with untargeted metabolomics, and second, to demonstrate the feasibility of the method by exploring serum/plasma and gender differences in 120 healthy young adults between 18 and 30 years of age. A range of analytical columns (C18 and biphenyl columns) and mobile phases (acidic and alkaline) were systematically evaluated. The optimized LC-MS method was based on a biphenyl column, a water-methanol gradient with 0.2% formic acid, and authentic isotope-labeled standards for each kynurenine metabolite. Precision and accuracy of targeted quantification of the key kynurenine metabolites tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and QUIN were excellent, far exceeding the acceptance criteria specified by international guidelines. Median inter- and intra-day precision were  0.70). Incurred sample reanalysis of 10% of the samples yielded a median difference
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2023.115304