Development of a liquid chromatography–mass spectrometry method for the determination of the neurotoxic quinolinic acid in human serum

Meinitzer, Andreas; Tomaschitz, Andreas; Pilz, Stefan; Truber, Manfred; Zechner, Gabriele; Gaksch, Martin; Prietl, Barbara; Treiber, Gerlies; Schwarz, Michaela; Baranyi, Andreas

doi:10.1016/j.cca.2014.06.010

Cited by 24 publications

(28 citation statements)

References 33 publications

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“…Concentrations of TRP, l-kynurenine (KYN), 3-hydroxykynurenine (HK), anthranilic acid (AA), kynurenic acid, xanthurenic acid (XA), quinolinic acid, picolinic acid, and nicotinic acid, were determined at the department of Laboratory Medicine of the University Medical Center Groningen by liquid chromatography in combination with isotope dilution tandem mass spectrometry (LC-MS/MS) essentially as described by [33]. In short, 100 µL of CSF or 50 µL of serum was mixed with deuterated or 13 C-labeled internal standards of the KP compounds under investigation.…”

Section: Lc-ms/msmentioning

confidence: 99%

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

et al. 2020

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Exploring the neurochemical continuum between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with respect to monoamines and kynurenines in cerebrospinal fluid (CSF) and serum, may be useful to identify possible new research/therapeutic targets. Hence, we analysed monoamines and kynurenines in CSF and serum derived from patients with FTD (n = 39), ALS (n = 23), FTD-ALS (n = 4) and age-matched control subjects (n = 26), using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) with electrochemical detection (ECD) and liquid chromatography tandem mass spectrometry, respectively. We noted a shared dopaminergic disturbance in FTD and ALS when compared to CONTR, with significantly increased serum DA levels and decreased DOPAC concentrations, as well as decreased DOPAC/DA ratios in both disease groups. In CSF, significantly reduced DOPAC concentrations in FTD and ALS were observed as well. Here, a significant increase in DA levels and decrease in DOPAC/DA ratios was only found in FTD relative to CONTR. With respect to the kynurenine pathway (KP), we only found decreased HK/XA ratios, indicative for vitamin B6 status, in serum of ALS subjects compared to FTD. The dopaminergic commonalities observed in FTD and ALS might relate to a disturbance of dopaminergic nerve terminals in projection areas of the substantia nigra and/or ventral tegmental area, although these findings should first be confirmed in brain tissue. Lastly, based on the results of this work, the KP does not hold promise as a research/therapeutic target in FTD and ALS.

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Section: Lc-ms/msmentioning

confidence: 99%

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

et al. 2020

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“…Plasma vitamin B-6 was measured as PLP by means of a validated HPLC method (Waters Alliance) with fluorescence detection (Jasco FP-2020; Jasco) (17). Plasma concentrations of 3-HK and XA were obtained with the use of validated liquid-chromatography-tandem mass spectrometry assays (18,19). The interassay CVs for 3-HK and XA were 9.7% and 2.7%, respectively.…”

Section: Data Collection and Measurementsmentioning

confidence: 99%

Functional vitamin B-6 status and long-term mortality in renal transplant recipients

Minovíc

Veen

Faassen

et al. 2017

The American Journal of Clinical Nutrition

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Background: Low plasma concentrations of pyridoxal 5#-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality. Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.

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“…To overcome the above challenges, we developed and validated herein a rapid and efficient method based on the technology of liquid chromatography-tandem mass spectrometry (LC-MS/MS), which shows superior performance in targeted metabolome studies, such as specificity, sensitivity, and sample throughput (Bennett et al, 2009;Luo, Groenke, Takors, Wandrey, & Oldiges, 2007). Certainly, there are numerous other techniques describing Trp and its metabolite measurement, including liquid chromatographic methods with UV and fluorescence detection as well as gas chromatography and liquid chromatography coupled to mass spectrometry (Badawy & Morgan, 2010;Eckstein, Ammerman, Reveles, & Ackermann, 2008;Meinitzer et al, 2014;Notarangelo, Wu, Macherone, Graham, & Schwarcz, 2012). However, our method could simultaneously monitor six closely related components spanning KP and 5-HT pathways of Trp ( Figure 1a) from brain tissue, serum, and CSF, which was also successfully used in characterizing the dynamics of these metabolic pathways in a streptozotocin (STZ)-induced DE rat model (Chmiel-Perzynska, Perzynski, & Urbanska, 2014;Kanth, Lavanya, & Srinivas, 2009).…”

mentioning

confidence: 99%

Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat

Han

Min

Wang

et al. 2017

J of Neuroscience Research

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Diabetic encephalopathy (DE), one of the most prevalent chronic complications of diabetes mellitus, is short of effective prevention and formidable therapeutic strategies. The aim of the present study is to reveal the imbalance of tryptophan (Trp) and its metabolites in streptozotocin (STZ)-induced experimental DE rats to underscore their critical values in clinical diagnosis of the disease.For this purpose, we first developed an accurate and appropriate simultaneous method for measuring Trp and its metabolites using liquid chromatography-tandem mass spectrometry, which was in accordance with the requirements of biological sample analysis. Secondly, a single STZ intraperitoneal injection was administered to male Sprague-Dawley rats, and their cognitive function was detected by Morris water maze tests. Cerebrospinal fluid (CSF), serum, and brain tissue were then collected for the determination of Trp and its metabolites. Compared with age-matched control rats, the levels of neuroprotective serotonin decreased significantly in the samples of cortices, hippocampi, striatum, CSF, and serums in the STZ-induced DE rats, while the levels of neurotoxic 3-hydroxykynurenine increased significantly. Moreover, analogous changes of both compounds were found in the central nervous system and peripheral blood of the STZ-induced DE rats. In conclusion, we established a quantitative method for the simultaneous detection of Trp and its metabolites, and we also present a critical elucidation of the nervous system dysfunction in DE.

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Development of a liquid chromatography–mass spectrometry method for the determination of the neurotoxic quinolinic acid in human serum

Cited by 24 publications

References 33 publications

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

Functional vitamin B-6 status and long-term mortality in renal transplant recipients

Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat

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