Determination of the kinetic rate constant of cyclodextrin supramolecular systems by high-performance affinity chromatography

Abstract

The kinetics of the association and dissociation are fundamental kinetic processes for the host–guest interactions (such as the drug–target and drug–excipient interactions) and the in vivo performance of supramolecules. With advantages of rapid speed, high precision and ease of automation, the high-performance affinity chromatography (HPAC) is one of the best techniques to measure the interaction kinetics of weak to moderate affinities, such as the typical host–guest interactions of drug and cyclodextrins by using a cyclodextrin-immobilized column. The measurement involves the equilibration of the cyclodex-trin column, the upload and elution of the samples (non-retained substances and retained solutes) at different flow rates on the cyclodextrin and control column, and data analysis. It has been indicated that cyclodextrin-immobilized chromatography is a cost-efficient high-throughput tool for the measurement of (small molecule) drug–cyclodextrin interactions as well as the dissociation of other supramolecules with relatively weak, fast, and extensive interactions.