QUANTITATIVE RELATIONSHIPS BETWEEN THE STRUCTURE OF BETA-ADRENOLYTIC AND ANTIHISTAMINE DRUGS AND THEIR RETENTION ON AN ALPHA(1)-ACID GLYCOPROTEIN HPLC COLUMN

Chromatographic retention parameters of a series of 7 beta-adrenolytic s and of 12 antihistamine drugs were determined employing an alpha1-ac id glycoprotein (AGP) high-performance liquid chromatographic (HPLC) c olumn. For the group of antihistamines capillary electrophoretic (CE) retention was additionally measured in the presence of either AGP or h uman serum albumin (HSA). Two series of solutes hydrophobicity paramet ers were obtained by reversed-phase HPLC on an immobilized artificial membrane (IAM) column. The solutes studied were subjected to molecular modelling and the structural descriptors obtained were applied in stu dies of quantitative structure-retention (protein binding) relationshi ps (QSRR). It was found that retention on AGP correlates well with the literature on physiological protein binding data. This retention was demonstrated to depend on hydrophobicity: to a lesser extent in the ca se of beta-adrenolytics and strongly in the case of antihistamines. Hy drophobicity, along with molecular width and electron excess charge on aliphatic nitrogen was demonstrated to describe retention of antihist amines on AGP. The AGP column is recommended as a convenient reactor f or studies of drug-protein interactions. Preliminary CE data do not co rrelate with the HPLC data.