[Investigation of association parameters of basic drugs to human serum albumin by capillary zone electrophoresis/frontal analysis].
A CZE/FA method was applied to the study of association parameters of basic drugs, verapamil (VER) and propranolol (PRO), to human serum albumin (HSA) under drug-HSA association equilibria. After the direct hydrodynamic injection of a drug-HSA mixed solution into a coated capillary (effective length, 32 cm; 50 microns i.d.), the basic drug is eluted as a zonal peak with a plateau region under condition of phosphate buffer (pH 7.4, ionic strength = 0.17) at 10 kV running voltage. The unbound concentration of drug can be determined from the plateau peak height with good linear response, r = 0.999 for both VER(n = 6) and PRO(n = 8), respectively. Six VER-HSA solutions (containing 50-175 mumol/L of VER and 450-325 mumol/L of HSA) and eight PRO-HSA solutions (containing 50-400 mumol/L of VER and 450-100 mumol/L of HSA) were investigated. Three analytical methods were used for the present CZE/FA system including Scatchard, Klotz and non-linear regression analyses. The estimated association parameters were as follows: the numbers of HSA binding site n for VER were over 1.21(0.04)-1.30(0.09), binding constant, K, was between 1,690(130) and 1,790(70). Whereas for PRO, n = 0.54(0.04)-0.62(0.03), and K = 1,390(70)-1,690(180). The data deduced from these three analyses agreed well with each other.
Ding
Y
Y
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023.
Zhu
X
X
Lin
B
B
D004347:Drug Interactions; D019075:Electrophoresis, Capillary / Q000379:methods; D006801:Humans; D011433:Propranolol / Q000032:analysis*; D012709:Serum Albumin / Q000032:analysis*; D014700:Verapamil / Q000032:analysis*
D012709:Serum Albumin; D011433:Propranolol; D014700:Verapamil