Investigation of microdialysis sampling calibration approaches for lipophilic analytes: doxorubicin

Microdialysis is an important sampling technique in many pharmacokinetics and pharmacological studies. Applying microdialysis to lipophilic analytes can be difficult as low extraction efficiencies are generally obtained with these types of analytes. In this investigation, the effects of applying microdialysis to the lipophilic compound, doxorubicin are discussed. Using varying concentrations of doxorubicin (DOX) from 1 to 20 microM, in vitro probe calibrations were performed by delivery, recovery and no-net flux. Any changes in the extraction efficiencies calculated were monitored through the addition of an internal standard, antipyrine. DOX was chosen as a representative lipophilic analyte because its red color could be visibly monitored on the probe. At higher concentrations the probe membrane became redder. For delivery experiments, the inlet of the probe was more highly colored than the outlet. The opposite was true for recovery experiments, in which the outlet was more highly colored than the inlet. It was observed that while antipyrine was well-behaved in these experiments, for DOX the extraction efficiency determined by recovery was not the same as the extraction efficiency determined by delivery (p<0.005, 0.05). It was further observed that for DOX the extraction efficiency determined by a no-net flux experiment was in good agreement with the value determined by delivery and not that determined by recovery. However, the only point in which no DOX was present in the perfusate was not on the no-net flux line. In addition, the transport of DOX across the microdialysis membrane was considerably slower than the transport of antipyrine.