Recent advances in chromatographic and electrophoretic methods for the study of drug-protein interactions.
Drug-protein binding is an important process in determining the activity and fate of a pharmaceutical agent once it has entered the body. This review examines various chromatographic and electrophoretic methods that have been developed to study such interactions. An overview of each technique is presented along with a discussion of its strengths, weaknesses and potential applications. Formats that are discussed include the use of both soluble and immobilized drugs or proteins, and approaches based on zonal elution, frontal analysis or vacancy peak measurements. Furthermore, examples are provided that illustrate the use of these methods in determining the overall extent of drug-protein binding, in examining the displacement of a drug by other agents and in measuring the equilibrium or rate constants for drug-protein interactions. Examples are also given demonstrating how the same methods, particularly when used in high-performance liquid chromatography or capillary electrophoresis systems, can be employed as rapid screening tools for investigating the binding of different forms of a chiral drug to a protein or the binding of different proteins and peptides to a given pharmaceutical agent.
Hage
D S
DS
Department of Chemistry, University of Nebraska-Lincoln, 68588-0304, USA.
Tweed
S A
SA
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010672:Phenytoin / Q000097:blood / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry; D014859:Warfarin / Q000097:blood / Q000737:chemistry
D004364:Pharmaceutical Preparations; D011506:Proteins; D012709:Serum Albumin; D014859:Warfarin; D010672:Phenytoin