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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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定量亲和色谱-质谱研究美洛昔康与β-环糊精的相互作用
, PP. 1167-1173
Keywords: 定量亲和色谱-质谱,美洛昔康,β-环糊精,解离速率常数
Abstract:
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(quantitativehigh-performanceaffinitychromatography),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±0.10s-1。根据美洛昔康的结合平衡常数k(12.53l·mol-1),计算得到表观结合速率常数kon,app为1.63l·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。
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