Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis

Citation
Xf. Zhu et al., Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis, ELECTROPHOR, 20(9), 1999, pp. 1869-1877
Citations number
35
Categorie Soggetti
Chemistry & Analysis
Journal title
ELECTROPHORESIS
ISSN journal
01730835 → ACNP
Volume
20
Issue
9
Year of publication
1999
Pages
1869 - 1877
Database
ISI
SICI code
0173-0835(199907)20:9<1869:SOEIBC>2.0.ZU;2-T
Abstract
The separation of the enantiomers of three basic drugs, i.e., ofloxacin, pr opranolol and verapamil, was achieved by affinity capillary electrophoresis (ACE), with human serum albumin (HSA) and bovine serum albumin (BSA) as ch iral selectors in phosphate buffer at pH 7.4. Ofloxacin was only separated in the presence of BSA, and verapamil only with HSA, while propranolol was separated with either HSA or BSA. The effects of protein concentration and column wall adsorption on the degree of separation were investigated. Two d isplacers, ketoprofen and warfarin, respectively, when added to the protein containing buffer, both showed significant effects on the separation behav ior. From these data it was argued that verapamil may bind to HSA at both l ocations known, the warfarin binding site (I) and the ketoprofen binding si te (II). While with BSA, binding of ofloxacin may also occur at site I, the preferential binding site for propanolol remains controversial. A drug-dru g interaction between propranolol and ketoprofen due to opposite charges wa s concluded from the increase in migration time in BSA solution. The unboun d concentration of verapamil enantiomers in solution in the presence of HSA , as estimated from CD-modified capillary zone electrophoresis, was trigger ed not only by the HSA concentration but also by the coadditive concentrati on.