Study of interaction between drug enantiomers and serum albumin by capillary electrophoresis

✍ Scribed by Yongsheng Ding; Xiaofeng Zhu; Bingcheng Lin

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 128 KB
• Volume: 20
• Category: Article
• ISSN: 0173-0835
• DOI: 10.1002/(sici)1522-2683(19990701)20:9<1890::aid-elps1890>3.0.co;2-e

✦ Synopsis

The interaction between drugs and human serum albumin (HSA) was investigated by capillary electrophoresis (CE). It involves stereoselectivity, drug displacement and synergism effects. Under protein-drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by frontal analysis (FA). The stereoselectivity of verapamil (VER) binding to HSA was proved by the different free fractions of two enantiomers. In physiological pH (7.4, ionic strength 0.17 phosphate buffer) when 300 mM () VER were equilibrated with 500 mM HSA, the concentration of unbound S-VER was about 1.7 times its antipode. The binding constants of two enantiomers, K R-VER and K S-VER , were 2670 and 850 M ±1 , respectively. However, no obvious stereoselective binding of propranolol (PRO) to HSA was observed. Trimethyl-b-cyclodextrin (45 mM) was used as a chiral selector in pH 2.5 phosphate buffer. Several drug systems were studied by the method. When ibuprofen (IBU) was added into VER-HSA solution. R-VER was partially displaced while S-VER was not displaced at all. A binding synergism effect between bupivacaine (BUP) and verapamil was observed and further study suggested that verapamil and bupivacaine occupy different binding site of HSA (site II and site III, respectively).