title: LC-MS/MS-based quantification of kynurenine metabolites, tryptophan, monoamines and neopterin in plasma, cerebrospinal fluid and brain.
abstract: OBJECTIVE
  The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will help elucidating the involvement of the KYN pathway in the disease pathology and inform drug development.
  
  
  METHODS
  Samples of plasma, cerebrospinal fluid or brain tissue were spiked with deuterated internal standards, processed and analyzed by LC-MS/MS; analytes were chromatographically separated by gradient elution on a C18 reversed phase analytical column without derivatization.
  
  
  CONCLUSIONS
  We established an LC-MS/MS method to measure 11 molecules, namely tryptophan, KYN, 3-OH-KYN, 3-OH-anthranilic acid, quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, serotonin, dopamine and neopterin within 5.5 min, with sufficient sensitivity to quantify these molecules in small sample volumes of plasma, cerebrospinal fluid and brain tissue.
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Fuertig
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ceci
authors.affiliation: Motac Neuroscience, Manchester, UK.
authors.forename: Sandrine M
authors.initials: SM
authors.lastname: Camus
authors.affiliation: Motac Neuroscience, Manchester, UK.|Univ de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.affiliation: Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Luippold
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Hengerer
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019798:Neopterin / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D017378:Quinolinic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry / Q000379:methods; D014364:Tryptophan / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D017378:Quinolinic Acid
keywords: IDO; LC; MS/MS; biomarker; indoleamine-2,3-dioxygenase; kynurenic acid; kynurenine; neopterin; neurotransmitters; quinolinic acid