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Quantitative microdialysis using modified ultraslow microdialysis: Direct rapid and reliable determination of free brain concentrations with the MetaQuant technique

Cremers, T. I. F. H., de Vries, M. G., Huinink, K. D., van Loon, J. P., Van der Hart, M., Ebert, B., Westerink, B. H. C. & De Lange, E. C. M., 15-Apr-2009, In : Journal of Neuroscience Methods. 178, 2, p. 249-254 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Thomas I. F. H. Cremers
  • Martin G. de Vries
  • Kirsten D. Huinink
  • Jan Paul van Loon
  • Marieke Van der Hart
  • Bjarke Ebert
  • Ben H. C. Westerink
  • Elizabeth C. M. De Lange

The only method to quantify free extracellular levels of drugs in the brain of living animals is microdialysis. However, quantitative microdialysis has been hampered by methodological issues for decades. The problems arise from the need to establish the in vivo recovery for appropriate quantitation. In dealing with these issues the "dynamic no-net-flux" (DNNF) method seemed to be the experimental method of choice. Major disadvantages were, however, the need for a very high degree of bioanalytical precision and accuracy and the need for a large number of animals. Moreover, today we know that the experimental data are not always straightforward.

To improve robustness and practicality of quantitative microdialysis sampling we modified the ultraslow microdialysis approach. Ultraslow microdialysis uses very low microdialysis flow rates (

In the current study we measured the free brain levels of two CNS compounds using the classic DNNF and the new modified ultraslow dialysis method.

Modified ultraslow microdialysis was shown to generate robust data with the use of only small numbers of rats. The method is a promising tool for common straightforward screening of blood-brain barrier penetration of compounds into the brain. (C) 2009 Published by Elsevier B.V.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalJournal of Neuroscience Methods
Volume178
Issue number2
Publication statusPublished - 15-Apr-2009

    Keywords

  • Quantitative, Microdialysis, Ultraslow, Recovery, Brain, Brain penetration, In vivo, P-GLYCOPROTEIN, INTRACEREBRAL MICRODIALYSIS, CEREBROSPINAL-FLUID, IN-VITRO, TRANSPORT, INVIVO, BLOOD, PHARMACOKINETICS, RETRODIALYSIS, CALIBRATION

ID: 4872466