Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding
Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding
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DOI：
10.1002/jps.21317
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发表时间：
2008-10-01
影响因子：
3.8
通讯作者：
Sohal, Bindi
中科院分区：
文献类型：
--
作者：
Waters, Nigel J.;Jones, Rachel;Sohal, Bindi
平衡透析（艾德）是研究药物结合的最常用方法之一，其中主要缺点是达到平衡的时间（在6和24小时之间变化）、长的测定制备时间和自动化的复杂性。快速平衡透析（RED）装置最近已上市（Pierce Biotechnology，ThermoFisher Scientific，Waltham，MA），可减少制备和平衡时间。RED装置包括一个Teflon基板，可容纳多达48个一次性透析池。每个透析插件由两个并排的腔室组成，腔室由具有高膜表面积与体积比的透析膜的垂直圆柱体分隔。作为与标准品艾德的比较分析，对测量人血浆蛋白结合率（PPB）的RED方法进行了独立验证，以评价平衡时间、试验重现性和准确度以及易用性。使用涵盖一系列理化性质的多种IS市售药物，我们已证明这是一种稳健且准确的方法，具有较短的制备和透析时间，能够自动化作为PPB测定的高通量测定。(C)2008威利利斯公司
Equilibrium dialysis (ED) is one of the most frequently used approaches to investigate drug binding, where the major drawbacks are the time to reach equilibrium (varying between 6 and 24 h), a long assay preparation time and complexity of automation. A rapid equilibrium dialysis (RED) device has recently become commercially available (Pierce Biotechnology, ThermoFisher Scientific, Waltham, MA) offering the potential for reduced preparation and equilibration times. The RED device comprises a Teflon base plate which holds up to 48 disposable dialysis cells. Each dialysis insert is made up of two side-by-side chambers separated by a vertical cylinder of dialysis membrane with a high membrane surface area-to-volume ratio. An independent validation of the RED approach for the measurement of human plasma protein binding (PPB) was carried out as a comparative analysis with standard ED evaluating equilibration time, assay reproducibility and accuracy and ease of use. Using a diverse set of IS commercially available drugs spanning a range of physicochemical properties we have shown this to be a robust and accurate methodology, with a shorter preparation and dialysis time, capable of being automated as a high-throughput assay for the determination of PPB. (C) 2008 Wiley-Liss, Inc.