High-performance affinity chromatography (HPAC) has been shown in the past to be a powerful tool for quickly examining the strength and rates of many biological interactions. This method makes use of a biologically-related agent, such as an immobilized protein, as the stationary phase. In the past, HPAC has been used with immobilized serum proteins and other binding agents to examine a number of drug-protein interactions in relatively simple systems. Recently, advances in the theory of HPAC and in the development of affinity microcolumns have made it possible to extend this approach to the analysis of more complex interactions, including those involving the direct analysis of drug-protein binding in clinical samples or in solution-phase samples.<br/><br/>This presentation will examine several applications and new approaches based on HPAC and affinity microcolumns that have been employed for examining enantioselective drug-protein interactions and measuring or studying chiral drugs in pharmaceutical and clinical samples. Examples of this work will include studies of the thermodynamics of drug-protein binding based on methods such as frontal analysis and zonal elution, as well as experiments employing newer techniques such as ultrafast affinity extraction. Analysis of the kinetics of these processes, as based on peak profiling, ultrafast affinity extraction and peak decay or peak height measurements will also be considered. These approaches will be illustrated by using a variety of chiral drugs and agents that can bind to these drugs, such as the proteins human serum albumin or alpha 1-acid glycoprotein and complex binding agents such as lipoproteins. The relative advantages of using HPAC and affinity microcolumns for these studies will be considered. In addition, several potential applications for these techniques will be discussed, including the design or optimization of chiral separations, high throughput drug screening, clinical testing, and personalized medicine.

Analysis of enantioselective drug-protein binding in pharmaceutical and clinical samples by high-performance affinity chromatography

252nd National Meeting (2016)

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