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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.

Funding

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.

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