Enhanced microdialysis recovery of some tricyclic antidepressants and structurally related drugs by cyclodextrin- mediated transport

Abstract

The enhanced microdialysis relative recovery (RR) of some hydrophobic tricyclic drugs (imipramine, desipramine, amitriptyline, carbamazepine and promethazine) is discussed. Enhanced RR was achieved by including a binding agent [β-cyclodextrin (β-CD) or 2-hydroxypropyl-β-cyclodextrin (HP-β-CD)] in the microdialysis perfusion fluid to form inclusion complexes with the drugs, which increases the analyte flux through the membrane material. The maximum effect of the RR increase for all the drugs studied was observed using a commercially available polycarbonate–polyether (PC) membrane. With a 4 mm PC membrane and 4.41 mmol l^–1 (0.5% w/v) β-CD included in the microdialysis perfusion fluid (0.9% saline, pH 7.4) at a flow rate of 0.5 µl min^–1, RR enhancements over controls were as follows: carbamazepine 136, imipramine 268, desipramine 298, amitriptyline 634, and promethazine 987%. Increasing β-CD [up to 17.63 mmol l^–1 (2% w/v)] or HP-β-CD [up to 32.5 mmol l^–1 (5% w/v)] concentration in the microdialysis perfusion fluid enhanced carbamazepine RR three (β-CD) to four (HP-β-CD) times compared to controls through PC microdialysis membranes. The PC membrane gave enhanced RR values that were twice those for cuprophan or AN-69 membranes. Enhanced RR with cyclodextrins was successfully applied to sampling from a protein solution containing desipramine in a 4% w/v bovine serum albumin solution. These results suggest that addition of cyclodextrins to microdialysis perfusion fluids may be used to increase microdialysis RRduring blood sampling.