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通过对RED膜插入物进行预处理提高药物-蛋白质结合未结合部分测量的准确性。

Improving the accuracy of unbound fraction measurement of drug-protein binding by preconditioning the RED membrane inserts.

作者信息

Ye Zhengqi, Chen Qing

机构信息

Drug Metabolism & Pharmacokinetics, Vertex Pharmaceuticals, Inc., Boston, MA 02210, USA.

出版信息

Bioanalysis. 2020 Dec;12(23):1699-1708. doi: 10.4155/bio-2020-0205. Epub 2020 Nov 12.

Abstract

The objective of this study was to evaluate the rapid equilibrium dialysis (RED) device in protein binding assays in diluted protein matrices and to improve the accuracy of the unbound fraction () measurement. Protein binding assays of drug compounds in bovine serum albumin solutions and human plasma with different folds of dilution were performed using the RED device with and without preconditioning of the dialysis membrane inserts, and the results were compared with those using other approaches in this study. Preconditioning of the RED membrane inserts improved the data accuracy of drug-protein binding assay in matrices with relatively low protein contents and such impact could be compound dependent.

摘要

本研究的目的是评估快速平衡透析(RED)装置在稀释蛋白质基质中的蛋白质结合测定中的性能,并提高未结合分数()测量的准确性。使用经过和未经过透析膜插入物预处理的RED装置,对不同稀释倍数的牛血清白蛋白溶液和人血浆中的药物化合物进行蛋白质结合测定,并将结果与本研究中使用其他方法得到的结果进行比较。RED膜插入物的预处理提高了蛋白质含量相对较低的基质中药物-蛋白质结合测定的 数据准确性,且这种影响可能因化合物而异。

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