Capillary hydrophilic interaction chromatography/mass spectrometry for simultaneous determination of multiple neurotransmitters in primate cerebral cortex.
A diverse array of neurotransmitters and neuromodulators control and affect brain function. A profound understanding of the signaling pathways and the neural circuits underlying behavior is therefore likely to require the tracking of concentration changes of active neurochemicals. In the present study, we demonstrate the feasibility of a method allowing the simultaneous determination of the concentrations of six neurotransmitters: acetylcholine, serotonin, dopamine, gamma-aminobutyric acid (GABA), glutamate and aspartate, in the extracellular brain fluid (EBF). We used hydrophilic interaction chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) to analyze the EBF from the monkey brain. A push-pull sampling method was used to collect EBF from the prefrontal cortex (PFC) of conscious monkeys at flow rates in the range of low nL/min. The detection limits of acetylcholine, serotonin, dopamine, GABA, glutamate and aspartate were 0.015, 0.15, 0.3, 1.2, 6 and 15 femtomoles, respectively, allowing us to quantitatively determine the concentrations of these six neurotransmitters simultaneously from 500 nL in vivo samples. We conclude that HILIC/MS/MS combined with the push-pull sampling method represents a sensitive technique for simultaneous monitoring of neurotransmitters from EBF samples.
Zhang
Xiaozhe
X
Max Plank Institute for Biological Cybernetics, 72076 Tubingen, Germany. xiaozhe.zhang@tuebingen.mpg.de
Rauch
Alexander
A
Lee
Han
H
Xiao
Hongbin
H
Rainer
Gregor
G
Logothetis
Nikos K
NK
D000818:Animals; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D045604:Extracellular Fluid / Q000737:chemistry; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000032:analysis*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014867:Water / Q000737:chemistry
D018377:Neurotransmitter Agents; D014867:Water