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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Xu, Xu Zhang, Jiwen Sun, Lixin Li, Haiyan He, Zhonggui Yang, Shuo York, Peter Ge, Jingwen Guo, Tao |
| Description | Country affiliation: China Author Affiliation: Li H ( Center for Drug Delivery System, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.) |
| 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 ß-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 ß-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. |
| ISSN | 00219673 |
| Volume Number | 1305 |
| e-ISSN | 18733778 |
| Journal | Journal of Chromatography A |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-08-30 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Chromatography, Affinity Methods Chromatography, High Pressure Liquid Beta-cyclodextrins Chemistry Acetaminophen Kinetics Models, Theoretical Sertraline Journal Article Research Support, Non-u.s. Gov't Discipline Analytical Chemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Medicine Analytical Chemistry Biochemistry |
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