Measurements of drug-protein binding by using immobilized human serum albumin liquid chromatography-mass spectrometry

Measurements of drug-protein binding by using immobilized human serum albumin liquid chromatography-mass spectrometry
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DOI:
10.1016/j.jchromb.2004.06.006
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发表时间:
2004-09-25
影响因子:
3
通讯作者:
Tseng, HL
Tseng, HL
中科院分区:
医学3区
文献类型:
--
作者:
Cheng, Y;Ho, E;Tseng, HL

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采用人血清白蛋白亲和柱,建立了一种基于HPLC/MS的药物血浆-蛋白质相互作用的快速简便测定方法。将该方法的结果与超滤或透析方法的数据进行比较,观察到良好的一致性。由于与超滤装置的人工膜的非特异性结合非常高而不适合超滤的化合物也通过该方法成功地分析,并且通过该色谱法测定的蛋白结合与通过采用生物膜的透析技术获得的数据非常相似。与超滤法相比,固定化HSA柱LC/MS法在药物蛋白结合率测量中也被证明具有更高的重现性和精确度。(C)2004 Elsevier B. V.保留所有权利。
An HPLC/MS based method was used for fast and convenient determination of drug plasma-protein interactions in early drug discovery screening by employing a human serum albumin affinity column. Results from this methodology were compared with data from ultrafiltration or dialysis methods, and good agreement was observed. A compound not suitable for ultrafiltration due to the very high non-specific binding to artificial membrane of ultrafiltration device was also successfully analyzed by this method, and the protein binding determined by this chromatography method was very similar to data obtained by dialysis technique employing biological membranes. The immobilized HSA column LC/MS method also proved to be more reproducible and precise compared to ultrafiltration method in drug protein binding measurements. (C) 2004 Elsevier B.V. All rights reserved.