定量亲和色谱-质谱研究美洛昔康与β-环糊精的相互作用

发布时间：2018-05-13 05:20

本文选题：定量亲和色谱-质谱 + 美洛昔康　；参考：《药学学报》2015年09期

【摘要】：药物与环糊精的结合速率常数、解离速率常数是药物从给药系统中解离、吸收的基本动力学常数,但现有研究多集中于结合平衡常数K。本文基于定量亲和色谱技术(quantitative high-performance affinity chromatography),发展了测定药物-环糊精超分子表观解离速率常数(koff,app)的定量亲和色谱-质谱方法。采用质谱检测器,经色谱峰拟合获得不同流速下药物和不保留物质尿嘧啶在β-环糊精柱上的保留时间与半峰宽,计算药物与不保留物质尿嘧啶的塔板高度(HR与HM,C);根据药物和不保留物质尿嘧啶的扩散系数差异与静态流动相传质阻抗,计算获得理论不保留物质的塔板高度HM,T。以(HR-HM,T)对uk/(1+k)2进行线性回归,根据斜率计算得到多流速条件下美洛昔康和对照药物(对乙酰氨基酚)的koff,app分别为0.13±0.00和4.83±0.10 s-1。根据美洛昔康的结合平衡常数K(12.53 L·mol-1),计算得到表观结合速率常数kon,app为1.63 L·mol-1·s-1。本法简便快速、重复性好,为评价药物与β-环糊精相互作用动力学提供了新的方法。
[Abstract]:The rate constant of drug binding to cyclodextrin, the dissociation rate constant, is the basic kinetic constant of drug dissociation and absorption from the drug delivery system, but most of the existing studies focus on the binding equilibrium constant K. Based on quantitative high-performance affinity chromatographic technique, a quantitative affinity chromatography-mass spectrometry method for the determination of the apparent dissociation rate constant of cyclodextrin was developed. The retention time and half peak width of uracil and uracil at different flow rates on 尾 -cyclodextrin column were obtained by using mass spectrometer. According to the difference of diffusion coefficient between drug and non-retention substance uracil and static flow phase mass transfer impedance, the height of tray with no retention matter was calculated. The linear regression of uk/(1 kan2 was carried out by HR-HMMT. According to the slope calculation, the koffophane of meloxicam and the control drug (paracetamol) were 0.13 卤0.00 and 4.83 卤0.10 s-1, respectively. According to the binding equilibrium constant of meloxicam, the apparent binding rate constant was calculated to be 1.63L mol-1 s-1. The method is simple, rapid and reproducible. It provides a new method for evaluating the interaction kinetics of 尾 -cyclodextrin.
【作者单位】：沈阳药科大学;中国科学院上海药物研究所;
【基金】：国家自然科学基金资助项目(81373358)
【分类号】：R927.2;O657.63

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