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Validation of LC–MS/MS methods for quantitative analysis of kynurenine pathway metabolites in human plasma and cerebrospinal fluid: supplementary materials

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posted on 2023-05-12, 07:49 authored by Vinod Khetarpal, Todd Herbst, Shahzad Akhtar, Amber LaFayette, Dennis Miller, James Farnham, Troy Steege, Zhixin Mia, Bryan Marks, Aaron Ledvina, Celia Dominguez

Background: Dysregulation of the kynurenine metabolic pathway has been reported in several

neurological conditions. Methods & results: Sensitive and selective LC–MS/MS methods have been

validated for six kynurenine pathway metabolites in human cerebrospinal fluid and plasma. For each

matrix, we validated three methods – one for the simultaneous determination of kynurenine, kynurenic

acid, anthranilic acid and 3-hydroxy-kynurenine (four-analyte assay), one for quinolinic acid and one for

tryptophan – using stable-isotopically labeled internal standards. The dynamic range and quantitation

limits were based on endogenous concentrations for each analyte. Conclusion: The use of validated

methods for kynurenine pathway metabolites in human cerebrospinal fluid and plasma will provide

definitive information in neurological diseases.


This work was funded by CHDI Foundation (https://chdifoundation.org/), a nonprofit biomedical research organization, whose sole mission is to accelerate therapeutic development for Huntington’s disease. V Khetarpal, T Herbst and C Dominguez are employees of CHDI Management, which supports CHDI Foundation. All data reported in this publication were generated by Labcorp Early Development Laboratories, Inc. (WI, USA), under a fee-for-service agreement.