A Method for Estimation of Plasma Protein Binding Using Diffusion Ordered NMR Spectroscopy (DOSY)

Abstract

The plasma protein binding (PPB) of a drug plays a key role in both its pharmacokinetic and pharmacodynamic properties. During lead optimisation, medium and high throughput methods for the early determination of PPB can provide important information about potential PKPD profile within a chemotype or between different chemotype series. Diffusion ordered spectroscopy (DOSY) is an NMR spectroscopic technique that measures the diffusion of a molecule via applying varying magnetic field gradients, where the diffusion is primarily affected by its molecular size/weight and solution viscosity. Here, we describe the use of DOSY for a rapid and straight forward method to evaluate the PPB of drug molecules, using their binding to bovine serum albumin (BSA) as a model.