Affinity capillary electrophoresis for the study of statin drug interactions with plasma proteins
B. Nigovic
Biljana Nigovic
Department of Analytics and Control of Medicines
Faculty of Pharmacy and Biochemistry,
University of ZagrebTrg maršala Tita 14
HR-10002 ZAGREB, CROATIA
Abstract:
An important topic in the discovery and development of new drugs is the role of drug binding to serum proteins. Drug-protein interactions are determining factors in the therapeutic and toxicological drug properties. Capillary electrophoresis has become a powerful tool in determining binding constants of formed drug-protein complexes. It offers some advantages in this kind of studies such as low sample requirement, short analysis time, high separation efficiency, sample throughput and low running costs.
A new affinity capillary electrophoresis method was developed for the estimation of binding constant of statin drugs. In order to simulate physiological conditions, the electrophoresis was carried out using a phosphate buffer pH 7.4. Measurements were conducted at ten different protein concentrations added in the running buffer, while the drug was kept at the constant concentration in the sample.
The apparent mobility of drug depends on the binding constant and the difference between the electrophoretic mobilities of free drug and drug-protein complex. Estimated values of binding constants were related with the structures of statins. The binding constants obtained by CE may help in early evaluation of drugs pharmacokinetic profiles during drug discovery.
