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.
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.
J Chromatogr A. 2014 Sep 12;1359:287-95. doi: 10.1016/j.chroma.2014.07.012. Epub 2014 Jul 15.
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.
环糊精超分子的形成和体内性能的基础是其解络动力学。使用高效亲和色谱（HPAC）单独确定表观离解速率常数（kd，app）是一个繁琐的过程，需要进行大量的单独研究和大量的数据拟合。在这项研究中，采用多分析物方法，通过一次注射同时测量三种药物的 kd，app 值，这是基于对药物-环糊精相互作用动力学对流动相组成的依赖性的研究。结果表明，当离子强度降低、药物离解度增加和加入额外有机溶剂时，kd，app 值增加。通过多分析物方法估算的对乙酰氨基酚、非那西丁和 S-氟比洛芬的 kd，app 值分别为 8.54±1.81、5.36±0.94 和 0.17±0.02s(-1)，与单独测定的值（8.31±0.58、5.01±0.42 和 0.15±0.01s(-1)）吻合较好。对于单一流速峰形分析和多流速峰形分析两种方法，多分析物方法的结果对于三种药物的单化合物分析在统计学上都是等效的（p>0.05）。多分析物方法可用于有效评价药物-环糊精动力学，环糊精柱泄漏引起的变化较小。
