title: Determination of the kinetic rate constant of cyclodextrin supramolecular systems by high performance affinity chromatography.
abstract: It is challenging and extremely difficult to measure the kinetics of supramolecular systems with extensive, weak binding (Ka<10(5)M(-1)), and fast dissociation, such as those composed of cyclodextrins and drugs. In this study, a modified peak profiling method based on high performance affinity chromatography (HPAC) was established to determine the dissociation rate constant of cyclodextrin supramolecular systems. The interactions of β-cyclodextrin with acetaminophen and sertraline were used to exemplify the method. The retention times, variances and the plate heights of the peaks for acetaminophen or sertraline, conventional non-retained substance (H2O) on the β-cyclodextrin bonded column and a control column were determined at four flow rates under linear elution conditions. Then, plate heights for the theoretical non-retained substance were estimated by the modified HPAC method, in consideration of the diffusion and stagnant mobile phase mass transfer. As a result, apparent dissociation rate constants of 1.82 (±0.01)s(-1) and 3.55 (±0.37)s(-1) were estimated for acetaminophen and sertraline respectively at pH 6.8 and 25°C with multiple flow rates. Following subtraction of the non-specific binding with the support, dissociation rate constants were estimated as 1.78 (±0.00) and 1.91 (±0.02)s(-1) for acetaminophen and sertraline, respectively. These results for acetaminophen and sertraline were in good agreement with the magnitude of the rate constants for other drugs determined by capillary electrophoresis reported in the literature and the peak fitting method we performed. The method described in this work is thought to be suitable for other supramolecules, with relatively weak, fast and extensive interactions.
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: Jingwen
authors.initials: J
authors.lastname: Ge
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D002846:Chromatography, Affinity / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007700:Kinetics; D008962:Models, Theoretical; D020280:Sertraline / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D000082:Acetaminophen; D020280:Sertraline
keywords: Cyclodextrin supramolecular systems; Dissociation rate constant; High performance affinity chromatography; Modified peak profiling method; Plate height