Quantitative microdialysis for the in vivo measurement of carbamazepine, oxcarbazepine and their major metabolites in rat brain- and liver tissue and in blood using the internal standard technique

Abstract

Microdialysis as in vivo sampling technique in pharmacokinetic studies requires the estimation of the in vivo relative recovery in order to calculate unbound blood- and extracellular tissue concentrations of the compounds of interest. Therefore, the internal standard technique was evaluated in this study, as in vivo calibration method to determine true concentrations of carbamazepine, oxcarbazepine and their major metabolites in the extracellular fluid of brain- and liver tissue and in blood. As internal standard, 2-methyl-5H-dibenz(b,f)azepine-5-carboxamide (m-CBZ) was used. The compounds, metabolites and the internal standard were added to the perfusate and their in vivo relative loss was determined. The in vivo relative recovery of the compounds and metabolites was established using the slow perfusion method. It was found that the ratios of the in vivo relative loss or relative recovery of the compounds and metabolites to the relative loss of the internal standard remain constant in time for both tissues and for blood. It is concluded that with m-CBZ as internal standard, the internal standard technique is a useful in vivo calibration method to determine the true concentrations of carbamazepine, oxcarbazepine and their metabolites in the extracellular space of brain-and liver tissue and in blood.