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

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 (