Title:

Application of capillary electrophoresis/frontal analysis in drug-protein binding study

Author:

Gonciarz-Dytman, Anna

Subject:

capillary electrophoresis ; drug-protein binding ; equilibrium dialysis ; albumin ; dexamethasone

Abstract:

Drug–protein binding is an important process affecting the pharmacokinetics and activity of drug, since only the free drug can pass across biological membranes and get to its site of action. In recent years, high-performance techniques have been sought to assess physicochemical properties and to study the ADME profile of compounds.The aim of this study was to develop, optimize and validate methods for separating and determining the free fraction of dexamethasone (DXM) and pravastatin (PRA) using capillary electrophoresis/frontal analysis (CE/FA) to assess their binding to plasma proteins. CE/FA has been compared with equilibrium dialysis (ED), considered as reference method. The thermodynamics of the binding process of DXM and PRA to bovine and human albumin were evaluated. CE/FA was used to study binding of compounds with endothelial activity to blood proteins, and the relationship between physicochemical properties of the tested compounds and the degree of their binding to studied proteins were evaluated.CE/FA can be used in high-throughput screening of drug-protein binding at the early stage of drug discovery. An advantage of CE/FA over ED is the ability to directly measure the concentration of free fraction of a compound in a sample, what significantly reduces costs and shortens the duration of the analysis. It can be use to evaluate the thermodynamics of binding process.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmacja

Degree grantor:

Wydział Farmaceutyczny

Promoter:

Walczak, Maria

Date:

2018

Date issued:

2017

Type:

Praca doktorska

Call number:

ZB-128499

Language:

pol

Access rights:

nieograniczony