Analysis of drug interactions with high-density lipoprotein by high-performance affinity chromatography.
Analysis of drug interactions with high-density lipoprotein by high-performance affinity chromatography.
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DOI：
10.1016/j.ab.2009.10.017
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Hage DS
中科院分区：
文献类型：
--
作者：
Chen S;Sobansky MR;Hage DS
制备含有固定化脂蛋白的柱，用于通过高效亲和色谱法分析药物与这些颗粒的相互作用。通过使用它来检查高密度脂蛋白（HDL）与药物普萘洛尔或维拉帕米的结合来评估这种方法。HDL通过Schiff碱方法固定到硅胶上，并在pH 7.4下连续操作4 - 5天后，得到与普萘洛尔具有可重复结合的HPLC柱。前沿分析实验表明，R/S-普萘洛尔和HDL在37°C时发生了两种类型的相互作用：饱和结合，缔合平衡常数（Ka）为1.1-1.9 × 105 M−1，非饱和结合，总亲和力常数（n Ka）为3.7-4.1 × 104 M−1。在4 ° C和27°C下发现类似的结果。维拉帕米也有类似的行为，在37°C时，饱和位点的Ka值为6.0 × 104 M−1，非饱和位点的n Ka值为2.5 × 104 M−1。这些测得的亲和力与溶液相值有很好的一致性。结果表明，HPAC可用于研究药物与HDL的相互作用，提供的信息应该是有价值的，在获得更好的描述药物如何在体内转运。
Columns containing immobilized lipoproteins were prepared for the analysis of drug interactions with these particles by high-performance affinity chromatography. This approach was evaluated by using it to examine the binding of high density lipoprotein (HDL) to the drugs propranolol or verapamil. HDL was immobilized by the Schiff base method onto silica and gave HPLC columns with reproducible binding to propranolol over four to five days of continuous operation at pH 7.4. Frontal analysis experiments indicated that two types of interactions were occurring between R/S-propranolol and HDL at 37°C: saturable binding with an association equilibrium constant (Ka) of 1.1–1.9 × 105 M−1, and non-saturable binding with an overall affinity constant (n Ka) of 3.7–4.1 × 104 M−1. Similar results were found at 4 and 27°C. Verapamil also gave similar behavior, with a Ka of 6.0 × 104 M−1 at 37°C for the saturable sites and a n Ka value for the non-saturable sites of 2.5 × 104 M−1. These measured affinities gave good agreement with solution-phase values. The results indicated HPAC can be used to study drug interactions with HDL, providing information that should be valuable in obtaining a better description of how drugs are transported within the body.
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DOI：
10.1016/s0731-7085(99)00197-1
发表时间：
1999-12-01
影响因子：
3.4
作者：
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发表时间：
2008-07-01
影响因子：
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作者：
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影响因子：
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作者：
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