The use of microdialysis for the determination of plasma protein binding of drugs.

Microdialysis sampling was used for the determination of the protein binding and the free therapeutic drug concentration of drugs in plasma in vitro. Several drugs with varying extent of protein binding and for which the plasma monitoring is important were studied. To mimic the in vivo situation, an artificial blood vessel was constructed and filled with spiked plasma circulating at the flow rate of human blood at 37 degrees C. The microdialysis probe (16 mm membrane length, 20000 MW cut off) was placed in the vessel and perfused with 0.9% NaCl at 5 microliters min-1. Dialysates were collected every 10 min and were analysed by reversed-phase LC with UV detection. The free concentration of the drug was calculated by correcting the concentration in the dialysate for the recovery of the probe, which was also determined in the artificial blood vessel after the experiment. The data confirm that microdialysis is a valid alternative technique for the determination of protein binding or free therapeutic plasma concentration of drugs on a comparative basis. Reference to literature values indicates that the results of the proposed method correspond reasonably well with accepted values.