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Analysis of Glutamate, GABA, Noradrenaline, Dopamine, Serotonin, and Metabolites Using Microbore UHPLC with Electrochemical Detection

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Antec BV, Industrieweg 12, 2382 NV Zoeterwoude, The Netherlands
Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacology, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands
Cite this: ACS Chem. Neurosci. 2013, 4, 5, 888–894
Publication Date (Web):May 3, 2013
https://doi.org/10.1021/cn400044s
Copyright © 2013 American Chemical Society
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Abstract

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The applicability of microbore ultrahigh performance liquid chromatography (UHPLC) with electrochemical detection for offline analysis of a number of well-known neurotransmitters in less than 10 μL microdialysis fractions is described. Two methods are presented for the analysis of monoamine or amino acid neurotransmitters, using the same UHPLC instrument. Speed of analysis of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and the metabolites homovanillic acid (HVA), 5-hydroxyindole aceticacid (5-HIAA), and 3,4-dihydroxyphenylacetic acid (DOPAC) was predominated by the retention behavior of NA, the nonideal behavior of matrix components, and the loss in signal of 5-HT. This method was optimized to meet the requirements for detection sensitivity and minimizing the size of collected fractions, which determines temporal resolution in microdialysis. The amino acid neurotransmitters glutamate (Glu) and γ-aminobutyric acid (GABA) were analyzed after an automated derivatization procedure. Under optimized conditions, Glu was resolved from a number of early eluting system peaks, while the total runtime was decreased to 15 min by a 4-fold increase of the flow rate under UHPLC conditions. The detection limit for Glu and GABA was 10 nmol/L (15 fmol in 1.5 μL); the monoamine neurotransmitters had a detection limit between 32 and 83 pmol/L (0.16–0.42 fmol in 5 μL) in standard solutions. Using UHPLC, the analysis times varied from 15 min to less than 2 min depending on the complexity of the samples and the substances to be analyzed.

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  14. Manuel Gesto. Characterization of the neuroendocrine stress status as part of the multiparametric assessment of welfare in fish. 2022, 285-308. https://doi.org/10.1016/B978-0-12-822273-7.00001-X
  15. Nurul H.M. Yusoff, Zurina Hassan, Vikneswaran Murugaiyah, Christian P. Müller. The effect of mitragynine on extracellular activity of brain dopamine and its metabolites. Brain Research Bulletin 2022, 178 , 1-8. https://doi.org/10.1016/j.brainresbull.2021.11.002
  16. Sung Sik Chu, Paul Marsh, Hung A. Nguyen, Carolyn E. Jones, Miranda M. Lim, Hung Cao. Fabrication of Highly Sensitive Pt-black Electrochemical Sensors for GABA Detection. 2021, 7148-7151. https://doi.org/10.1109/EMBC46164.2021.9630176
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  41. Yunyun Huang, Mingfei Ding, Tuan Guo, Ning Zhang, Zhuang Tian, Li-Peng Sun, Bai-Ou Guan. Ultrasensitive and label-free detection of γ-aminobutyric acid using fiber-optic interferometric sensors functionalized with size-selective molecular sieve arrays. Sensors and Actuators B: Chemical 2017, 244 , 934-940. https://doi.org/10.1016/j.snb.2017.01.031
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  43. Mingfei Ding, Yunyun Huang, Tuan Guo, Li-Peng Sun, Bai-Ou Guan. Mesoporous nanospheres functionalized optical microfiber biosensor for low concentration neurotransmitter detection. Optics Express 2016, 24 (24) , 27152. https://doi.org/10.1364/OE.24.027152
  44. Anne Marie V. Schou-Pedersen, Stine N. Hansen, Pernille Tveden-Nyborg, Jens Lykkesfeldt. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain. Journal of Chromatography B 2016, 1028 , 222-230. https://doi.org/10.1016/j.jchromb.2016.05.048
  45. Jolien Van Schoors, Johan Viaene, Yannick Van Wanseele, Ilse Smolders, Bieke Dejaegher, Yvan Vander Heyden, Ann Van Eeckhaut. An improved microbore UHPLC method with electrochemical detection for the simultaneous determination of low monoamine levels in in vivo brain microdialysis samples. Journal of Pharmaceutical and Biomedical Analysis 2016, 127 , 136-146. https://doi.org/10.1016/j.jpba.2016.01.015
  46. Yan Zhang, Yi Zhang, Guan Wang, Wujuan Chen, Yi Li, Yating Zhang, Pingang He, Qingjiang Wang. Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking. Journal of Chromatography B 2016, 1025 , 33-39. https://doi.org/10.1016/j.jchromb.2016.04.054
  47. Jolien Van Schoors, Katrien Maes, Yannick Van Wanseele, Ken Broeckhoven, Ann Van Eeckhaut. Miniaturized ultra-high performance liquid chromatography coupled to electrochemical detection: Investigation of system performance for neurochemical analysis. Journal of Chromatography A 2016, 1427 , 69-78. https://doi.org/10.1016/j.chroma.2015.11.076
  48. Wei-feng Wang, Fu-rong Ju, Yan-li Ran, Hui-ge Zhang, Xing-guo Chen. Detection of biogenic amines in C57BL/6 mice brain by capillary electrophoresis electrokinetic supercharging. The Analyst 2016, 141 (3) , 956-962. https://doi.org/10.1039/C5AN01642H
  49. Jolien Van Schoors, Charlotte Lens, Katrien Maes, Yvette Michotte, Ilse Smolders, Ann Van Eeckhaut. Reassessment of the antioxidative mixture for the challenging electrochemical determination of dopamine, noradrenaline and serotonin in microdialysis samples. Journal of Chromatography B 2015, 998-999 , 63-71. https://doi.org/10.1016/j.jchromb.2015.06.010
  50. Yaqiong Xu, Xu Hun, Fang Liu, Xiaolong Wen, Xiliang Luo. Aptamer biosensor for dopamine based on a gold electrode modified with carbon nanoparticles and thionine labeled gold nanoparticles as probe. Microchimica Acta 2015, 182 (9-10) , 1797-1802. https://doi.org/10.1007/s00604-015-1509-5
  51. Zachary D. Brodnik, George E. Jaskiw. Effect of Mobile Phase pH on the Function of Other Optimization Parameters in an HPLC–ECD Assay of Biogenic Amines and Their Metabolites. Journal of Liquid Chromatography & Related Technologies 2015, 38 (4) , 467-471. https://doi.org/10.1080/10826076.2014.913525
  52. Jia Xu, Zhonglian Qian, Libo Zhao, Yi Fang. An optimized HPLC/MS/MS method for quantification of excitatory amino acids in rat hippocampus and its application in brain ischemia/reperfusion research. Biomedical Chromatography 2014, 28 (12) , 1822-1827. https://doi.org/10.1002/bmc.3226
  53. Jolien Van Schoors, Hendrik-Jan Brouwer, Katrien Maes, Yvette Michotte, Ann Van Eeckhaut. Ion-pair ultra-high performance liquid chromatographic analysis of monoamines: Peak-splitting at high flow rates. Journal of Chromatography A 2013, 1321 , 73-79. https://doi.org/10.1016/j.chroma.2013.10.070

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