LC-MS/MS-based quantification of kynurenine metabolites, tryptophan, monoamines and neopterin in plasma, cerebrospinal fluid and brain

被引：117

作者：

Fuertig, Rene ^{[1
]}

Ceci, Angelo ^{[1
]}

Camus, Sandrine M. ^{[2
]}

Bezard, Erwan ^{[2
,3
,4
]}

Luippold, Andreas H. ^{[5
]}

Hengerer, Bastian ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharma GmbH & Co KG, CNS Dis Res, Birkendorfer Str 65, D-88397 Biberach, Germany

[2] Motac Neurosci, Manchester, Lancs, England

[3] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France

[4] CNRS, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France

[5] Boehringer Ingelheim Pharma GmbH & Co KG, Drug Discovery Support, Birkendorfer Str 65, D-88397 Biberach, Germany

来源：

BIOANALYSIS | 2016年 / 8卷 / 18期

关键词：

biomarker; IDO; indoleamine-2,3-dioxygenase; kynurenic acid; kynurenine; LC; neopterin; neurotransmitters; quinolinic acid; MS/MS; MASS-SPECTROMETRY METHOD; NEURONAL CELL-DEATH; 3-HYDROXYLASE INHIBITION; GTP-CYCLOHYDROLASE; INTERFERON-GAMMA; QUINOLINIC ACID; IFN-GAMMA; RECEPTOR; IMMUNE; BIOSYNTHESIS;

D O I：

10.4155/bio-2016-0111

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Aim: 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. Methodology: 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. Conclusion: 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.

引用

页码：1903 / 1917

页数：15

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