Assessment of the recovery of three lipophilic psoralens by microdialysis: an in vitro study

The microdialysis method is extensively developed in neuropharmacological experiments. It is a non-invasive technique with promising applications in biological research. The aim of this work was to establish and to optimize a process to microdialyse chemicals. Three lipophilic molecules used in dermatology were tested: 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and trimethylpsoralen (TMP). These psoralens have the same basic chemical structure (furocoumarin). The different radical substitutions are responsible for their different lipophilicities. In this work, different microdialysis parameters were studied: the relative recovery and the equilibrium time in relation to the perfusion rate and to the drug lipophilicity. The equipment was composed of a CMA/100® microinjection pump, CMA/20® microdialysis probes (membrane length of 10 mm, cut off 20 and 100 kDa) and a CMA/140® microcollector. The perfusate was a phosphate buffer 0.06 M (pH 7.4). The psoralen dialysates were assessed by high performance liquid chromatography. The relative recovery of psoralens increased with the decreasing perfusion rates and with the drug lipophilicity. The equilibrium time decreased with the increasing perfusion rates. TMP was not detected under these experimental conditions. This work defines the optimal parameters for in vivo studies and shows the limit of this technique for the investigation of lipophilic drugs.