Chromatographic hydrophobicity parameter determined on an immobilized artificial membrane column: relationships to standard measures of hydrophobicity and bioactivity

Abstract

A dynamic chromatographic hydrophobicity parameter, log k′ IAM was determined for 3 test series of drug solutes (β-adrenolytics, imidazoline α-adrenomimetics and phenothiazine neuroleptics) employing a reversed-phase high-performance liquid chromatographic (RP HPLC) system comprising an immobilized artificial membrane (IAM) column. The log k′ IAM parameter determined with buffers of physiological pH correlated well with the ionization-corrected reference hydrophobicity parameters from the n-octanol/water system in the case of β-adrenolytics ( r = 0.962) but a poorer correlation ( r = 0.839) was noted in the case of phenothiazines. Regression analysis of several pharmacokinetic data reported for the agents under study in terms of hydrophobicity parameters demonstrated the performance of log k′ IAM to be as good as that of the reference hydrophobicity parameters in predicting bioactivity. There is an important advantage of the log k′ IAM parameter over n-octanol/water partition data, which are tedious to determine: log k′ IAM is derived in a simple, fast and reproducible manner.