Measuring multiple neurochemicals and related metabolites in blood and brain of the rhesus monkey by using dual microdialysis sampling and capillary hydrophilic interaction chromatography-mass spectrometry |
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Authors: | Li Juan von Pföstl Veronika Zaldivar Daniel Zhang Xiaozhe Logothetis Nikos Rauch Alexander |
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Institution: | (1) Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 T?bingen, Germany;(2) Department of Medicine, University of Fribourg, Chemin de Musee 5, Fribourg, 1700, Switzerland;(3) Division of Imaging Science and Biomedical Engineering, University of Manchester, Manchester, M13 9PT, UK;(4) Graduate School of Neural and Behavioural Science/International Max Planck Research School, University T?bingen, 72074 T?bingen, Germany; |
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Abstract: | In vivo measurement of multiple functionally related neurochemicals and metabolites (NMs) is highly interesting but remains
challenging in the field of basic neuroscience and clinical research. We present here an analytical method for determining
five functionally and metabolically related polar substances, including acetylcholine (quaternary ammonium), lactate and pyruvate
(organic acids), as well as glutamine and glutamate (amino acids). These NMs are acquired from samples of the brain and the
blood of non-human primates in parallel by dual microdialysis, and subsequently analyzed by a direct capillary hydrophilic
interaction chromatography (HILIC)–mass spectrometry (MS) based method. To obtain high sensitivity in electrospray ionization
(ESI)–MS, lactate and pyruvate were detected in negative ionization mode whereas the other NMs were detected in positive ionization
mode during each HILIC-MS run. The method was validated for linearity, the limits of detection and quantification, precision,
accuracy, stability and matrix effect. The detection limit of acetylcholine, lactate, pyruvate, glutamine, and glutamate was
150 pM, 3 μM, 2 μM, 5 nM, and 50 nM, respectively. This allowed us to quantitatively and simultaneously measure the concentrations
of all the substances from the acquired dialysates. The concentration ratios of both lactate/pyruvate and glutamine/glutamate
were found to be higher in the brain compared to blood (p < 0.05). The reliable and simultaneous quantification of these five NMs from brain and blood samples allows us to investigate
their relative distribution in the brain and blood, and most importantly paves the way for future non-invasive studies of
the functional and metabolic relation of these substances to each other. |
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