Abstract
A novel parameter of relative recovery (Rre) was defined and determined by online SPE-HPLC to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs. The proportional relationship of Rre with koff of PPB has been established with a new SPE model. A rapid, easy to use method could potentially be used to categorize PK properties of the drug candidates in the decision process of drug discovery and development.
Highlights
A novel parameter of relative recovery (Rre) was defined and determined by online Solid phase extraction (SPE)-high performance liquid chromatography (HPLC) to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs
This study provides a novel, simple and easy to use approach to characterize PPB dissociation of a drug and thereby help to explain and predict the in vivo phenomena of a drug
Low Rre means only a small part of unbound drugs were retained in SPE column when the drugs were loaded on SPE column in presence of plasma
Summary
A novel parameter of relative recovery (Rre) was defined and determined by online SPE-HPLC to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs. Free drug theory (FDT)[1,2,3] is widely accepted to explain how the PPB of a drug relates to its in vivo phenomena: the binding of a drug is taken as a reversible and rapid equilibrium process[2,4] resulting in the constant and instantaneous concentration of unbound (free) drug. Measurement of the bound drug fraction of a compound (percentage of plasma protein binding) using an in vitro PPB assay is a common practice in drug discovery and is a requirement for new drug application. The percentage of plasma protein binding is a value related to the equilibrium constant in a permanent state. The dissociation constant (Kd) can be defined as follows[4,9]: www.nature.com/scientificreports/
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