A Novel, Robust Method for Quantification of Multiple Kynurenine Pathway Metabolites in the Cerebrospinal Fluid
Lilly Schwieler, Ada Trepci, Stanisław Krzyżanowski, Sigurd Hermansson, Mathias Granqvist, Fredrik Piehl, Tomas Venckūnas, Marius Brazaitis, Sigitas Kamandulis, Daniel Lindqvist, A. Daniel Jones, Sophie Erhardt, Lena Brundin
Abstract
Aim: Kynurenine metabolites are potential modulators of psychiatric disease. We aimed to develop a highly sensitive biochemical analysis of cerebrospinal fluid (CSF) tryptophan (TRP) metabolites, to investigate the stability of metabolites and to confirm our previous findings of aberrant CSF quinolinic acid (QUIN) and picolinic acid (PIC) in suicide attempters using this method. Methodology & results: Ten CSF TRP metabolites were analyzed with ultraperformance LC–MS/MS. The method showed small intra- and interassay variation. Metabolites were stable following freeze–thaw cycles. A decreased CSF PIC/QUIN ratio was found in suicide attempters. Conclusion: The feasibility of reliably determining CSF TRP metabolites were demonstrated, including separation of the two isomers PIC and nicotinic acid (NA) and the finding of a reduced PIC/QUIN ratio replicated in suicide attempters.