title: Multianalyte determination of the kinetic rate constants of drug-cyclodextrin supermolecules by high performance affinity chromatography.
abstract: The kinetics of the dissociation is fundamental to the formation and the in vivo performance of cyclodextrin supramolecules. The individual determination of the apparent dissociation rate constant (kd,app) using high performance affinity chromatography (HPAC) is a tedious process requiring numerous separate studies and massive data fitting. In this study, the multianalyte approach was employed to simultaneously measure the kd,app values of three drugs through one injection based on the investigation of the dependence of drug-cyclodextrin interaction kinetics on the mobile phase composition. As a result, the kd,app values increased when decreasing the ion strength, increasing the ionization of drugs and adding extra organic solvents. The values of kd,app for acetaminophen, phenacetin and S-flurbiprofen estimated by the multianalyte approach were 8.54±1.81, 5.36±0.94 and 0.17±0.02s(-1), respectively, which were in good agreement with those determined separately (8.31±0.58, 5.01±0.42 and 0.15±0.01s(-1)). For both of the single and multiple flow rate peak profiling methods, the results of the multianalyte approach were statistically equivalent with that of the single compound analysis for all of the three drugs (p>0.05). The multianalyte approach can be employed for the efficient evaluation of the drug-cyclodextrin kinetics with less variance caused by cyclodextrin column bleeding.
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Caifen
authors: C
authors: Wang
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Jingwen
authors: J
authors: Ge
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
authors: Jiwen
authors: J
authors: Zhang
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Tao
authors: T
authors: Guo
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Liandi
authors: L
authors: Chi
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Zhonggui
authors: Z
authors: He
authors: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
authors: Xu
authors: X
authors: Xu
authors: University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom. Electronic address: P.York@Bradford.ac.uk.
authors: Peter
authors: P
authors: York
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: slx04@163.com.
authors: Lixin
authors: L
authors: Sun
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: hyli@mail.shcnc.ac.cn.
authors: Haiyan
authors: H
authors: Li
mesh_terms: D000700:Analgesics / Q000737:chemistry*; D002846:Chromatography, Affinity / Q000295:instrumentation / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D005480:Flurbiprofen / Q000737:chemistry*; D007700:Kinetics; D010615:Phenacetin / Q000737:chemistry*
chemical_list: D000700:Analgesics; D003505:Cyclodextrins; D005480:Flurbiprofen; D010615:Phenacetin
keywords: Cyclodextrin supramolecular systems; Kinetic studies; Mobile phase composition; Modified peak profiling method; Multianalyte approach