Analytical and Bioanalytical Chemistry

, Volume 402, Issue 8, pp 2545–2554 | Cite as

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

  • Juan Li
  • Veronika von Pföstl
  • Daniel Zaldivar
  • Xiaozhe ZhangEmail author
  • Nikos Logothetis
  • Alexander RauchEmail author
Original Paper


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.


Measuring multiple polar multiple neurochemicals and related metabolites using HILIC-ESI/MS in combination with dual brain and blood sampling


Neurochemicals HILIC-MS Microdialysis Rhesus monkey Brain Blood 



This work was supported by the Max Planck Society and BMBF Grant, Nr. 01EV0701. We thank Nadine Serr and Ulrike Passlack-Memaj for assistance in chemical preparations. We thank Mark Augath for assistance with the monkey anesthesia.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Juan Li
    • 1
  • Veronika von Pföstl
    • 1
  • Daniel Zaldivar
    • 1
    • 4
  • Xiaozhe Zhang
    • 2
    Email author
  • Nikos Logothetis
    • 1
    • 3
  • Alexander Rauch
    • 1
    Email author
  1. 1.Max Planck Institute for Biological CyberneticsTübingenGermany
  2. 2.Department of MedicineUniversity of FribourgFribourgSwitzerland
  3. 3.Division of Imaging Science and Biomedical EngineeringUniversity of ManchesterManchesterUK
  4. 4.Graduate School of Neural and Behavioural Science/International Max Planck Research SchoolUniversity TübingenTübingenGermany

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