Investigation of microdialysis sampling calibration approaches for lipophilic analytes: Doxorubicin

Abstract

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 μM, 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.

Population Pharmacokinetic Modeling of the Unbound Levofloxacin Concentrations in Rat Plasma and Prostate Tissue Measured by Microdialysis

“…The no-net-flux (NNF) method used for probe calibration in vivo involves both recovery and delivery experiments in the same trial (21). The recovery determined in vivo was used to correct the actual interstitial concentrations from the subjects.…”

Investigation of Factors Affecting Microdialysis Probe Delivery and Recovery of Puerarin In Vitro

“…In Whitaker & Lunte's experiments [7], E D of the target compound, doxorubicin, was significantly higher than E R , which was ascribed to its strong absorption to membrane. The probe membrane became and remained red in color after perfusion also proved its absorption visually.…”

“…Key: ■ = delivery of 10 mm membrane; □ = recovery of 10 mm membrane; ▲= delivery of 2 mm membrane; △ = recovery of 2 mm membrane Whitaker and Lunte [7] found that the absorption of the membrane led to the difference between E D and E R . It was not feasible to replace E R with E D when adsorption existed.…”

Investigation of Factors Affecting Microdialysis Probe Delivery and Recovery of Puerarin In Vitro

“…In Whitakers experiments [7], the E D of the target compound, doxorubicin, was significantly higher than E R , which was ascribed to its strong absorption to membrane. The probe membrane became and remained red in color after perfusion also proved its absorption visually.…”

“…Whitaker [7] found that the absorption of the membrane led to the difference between E D and E R . It was not feasible to replace E R with E D when adsorption existed.…”