Enantioselective retention of β-blocking agents on human serum albumin and α1-acid glycoprotein HPLC columns: Relationships with different scales of lipophilicity

The enantioselective retention of thirteen β-blockers on HPLC stationary phases supporting human serum albumin (HSA) or α1-acid glycoprotein (AGP) was investigated. Eight β-blockers were enantiomerically resolved on the AGP column whereas only four β-blockers were resolved on the HSA column. Moreover, interactions between β-blockers and AGP were much stronger than those with HSA. Retention values on both HSA and AGP for less retained enantiomers related well with various lipophilicity parameters, with the best relationships found with log⁡kwIAM values obtained on HPLC stationary phases supporting phospholipids, i.e. the so-called Immobilized Artificial Membrane (IAM). Differently from n-octanol lipophilicity values, these values encode both lipophilic. Electrostatic intermolecular recognition forces which may be involved in the interaction between ionized analytes, such as β-blockers, and proteins. However, their effectiveness to describe non-specific interactions with serum–proteins for other classes of drugs needs further investigations. Analyses performed on AGP with eluent containing dimethyloctylamine (DMOA) as the displacer demonstrated that enantioselective sites bind to both (−)-forms and (+)-forms, but the binding to (−)-forms is stronger. The enantiomer competition to bind to a same site may be relevant from a pharmacokinetic point of view when racemic mixtures are administered.Finally, in contrast to previously reported data in the literature, we found that AGP can bind enantioselectively not only the more lipophilic congeners but also the less lipophilic ones.