Protein binding of some nonsteroidal anti-inflammatory drugs studied by high-performance liquid affinity chromatography

ArticleinInternational Journal of Pharmaceutics 180(1):69-74 · April 1999with7 Reads
DOI: 10.1016/S0378-5173(98)00397-4 · Source: PubMed
The protein binding of indomethacin, sulindak and diclofenac sodium is studied in the presence of some competitors: phenylbutazon and diazepam. A high-performance liquid affinity chromatography based on chiral stationary phases with immobilized human serum albumin is used. The competition of the markers and the drugs for two major high- and low-affinity binding sites is investigated. Using a mathematical procedure proposed by the same authors in a previous work the affinity constants of the binding drugs and markers for both types of site are calculated. An analogous behaviour is established for the three drugs-they have nearly the same affinity for the primary binding sites marked by phenylbutazon and diazepam and only one type of low-affinity site (diazepam-binding sites) is involved in binding. That can be explained assuming an overlapping sites.
  • Article · · Journal of Chromatography B
  • [Show abstract] [Hide abstract] ABSTRACT: The stereochemistry of drug and xenobiotic metabolism and toxicokinetics have recently become an issue for the pharmaceutical industry and the regulatory authorities. Chirality is an intrinsic property of macromolecular structures in the cells such as enzymes, receptors, and nucleic acids which becomes evident when they interact with a chiral drug or xenobiotic molecule, showing a high degree of stereoselectivity. There are now a range of examples of isomeric compounds whose biological activity may well reside predominantly in one enantiomer. The differences in the biological activities between enantiomers have resulted in an increased interest in determination of enantiomeric composition of drugs, xenobiotics, and/or their metabolites. The difficulty in determining enantiomeric excess arises from the fact that enantiomers have identical physicochemical properties in a non-chiral environment. The major analytical breakthrough has come with the emergency of commercially available chiral stationary phases for capillary gas chromatography, high-performance liquid chromatography, and capillary electrophoresis.
    Article · Oct 2000
  • [Show abstract] [Hide abstract] ABSTRACT: High-performance affinity chromatography (HPAC) is a method in which a biologically-related ligand is used as a stationary phase in an HPLC system. This approach is a powerful means for selectively isolating or quantitating agents in complex samples, but it can also be employed to study the interactions of biological systems. In recent years there have been numerous reports in which HPAC has been used to examine the interactions of drugs, hormones and other substances with serum proteins. This review discusses how HPAC has been used in such work. Particular attention is given to the techniques of zonal elution and frontal analysis. Various applications are provided for these techniques, along with a list of factors that need to be considered in their optimization and use. New approaches based on band-broadening studies and rapid immunoextraction are also discussed.
    Article · Mar 2002
Show more