Automated Plasma Protein Binding Using Rapid Equilibrium Dialysis

Automated Plasma Protein Binding Using Rapid Equilibrium Dialysis

Published:  06 February 2015

High Content Automated Plasma Protein Binding Screening and Definitive Assays Using Rapid Equilibrium Dialysis for Drug Development

A pharmacokinetic/pharmacodynamic principle important in drug development is that it is the free (unbound) and not the total dosed drug that exerts a pharmacological effect or is available for distribution, metabolism and clearance from the body. Plasma proteins such as albumin have a high propensity to bind drugs that are typically responsible for the bulk of non-specific in vivo drug binding. Therefore the extent of plasma protein binding (PPB) is a critical parameter to determine during drug development as it can influence efficacy factors such as receptor occupancy and disposition factors such as metabolic clearance. In the present study we developed automated methods for PPB screening and definitive PPB assessment on a Tecan liquid handler with endpoints measuring fraction unbound (fu), mass balance (% recovery) and plasma stability (% remaining). Rapid equilibrium dialysis was selected as the methodology of choice for PPB assessment as it is commonly used in the industry and amenable to automation.