title: Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis.
abstract: The separation of the enantiomers of three basic drugs, i.e., ofloxacin, propranolol and verapamil, was achieved by affinity capillary electrophoresis (ACE), with human serum albumin (HSA) and bovine serum albumin (BSA) as chiral 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 displacers, ketoprofen and warfarin, respectively, when added to the protein containing buffer, both showed significant effects on the separation behavior. From these data it was argued that verapamil may bind to HSA at both locations known, the warfarin binding site (I) and the ketoprofen binding site (II). While with BSA, binding of ofloxacin may also occur at site I, the preferential binding site for propanolol remains controversial. A drug-drug interaction between propranolol and ketoprofen due to opposite charges was concluded from the increase in migration time in BSA solution. The unbound concentration of verapamil enantiomers in solution in the presence of HSA, as estimated from CD-modified capillary zone electrophoresis, was triggered not only by the HSA concentration but also by the coadditive concentration.
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: B
authors.initials: B
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Jakob
authors.forename: B
authors.initials: B
authors.lastname: Koppenhoefer
mesh_terms: D000327:Adsorption; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification; D002417:Cattle; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D015242:Ofloxacin / Q000737:chemistry / Q000302:isolation & purification*; D011433:Propranolol / Q000737:chemistry / Q000302:isolation & purification*; D012709:Serum Albumin; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000302:isolation & purification; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification; D014700:Verapamil / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D000890:Anti-Infective Agents; D012709:Serum Albumin; D014665:Vasodilator Agents; D012710:Serum Albumin, Bovine; D011433:Propranolol; D015242:Ofloxacin; D014700:Verapamil