Study of Ion-Ion Interaction for Protein-Drug Binding using a Newly Developed Guanidino-Bonded Phase in Liquid Chromatography

Abstract

The chromatographic behavior of acidic drugs was studied using a guanidino phase in liquid chromatography. The quaternary anion-exchange group, i.e., the guanidino group, acted as a weak anion exchanger and the chromatographic retention capacity was similar to that of a DEAE ion exchanger. Acidic drugs were poorly retained on guanidino phase in a 50mM sodium phosphate buffer at pH7.4.

This finding explains why drug-protein binding constants are generally related to the hydrophobicity of drugs and why the ion-ion interaction has seemed not to contribute to the molecular interaction. The computational chemical analysis of the retention mechanism indicated that mainly electrostatic force contributes to the retention of drugs on the guanidino phase.