Retention of structurally diverse drugs in human serum albumin chromatography and its potential to simulate plasma protein binding
Retention of structurally diverse drugs in human serum albumin chromatography and its potential to simulate plasma protein binding
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DOI：
10.1016/j.chroma.2010.07.023
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发表时间：
2010-09-10
影响因子：
4.1
通讯作者：
Tsantili-Kakoulidou, Anna
中科院分区：
文献类型：
--
作者：
Chrysanthakopoulos, Marios;Giaginis, Costas;Tsantili-Kakoulidou, Anna
使用 PBS 缓冲液（pH 7.0）和乙腈或 2-丙醇作为有机改性剂，研究了 39 种结构不同的中性、碱性和酸性药物在 HSA 固定相上的保留行为。外推或直接测量的 log k(w) 值以及等度保留因子与从文献中获取的血浆蛋白结合数据相关。在 10% 乙腈存在的情况下测定的保留因子与表观 K-HSA 的 log 值形成高质量的 1:1 相关性。使用第二组 24 种药物成功验证了导出的参考方程。对 HSA 保留更基本特性的进一步分析揭示了阴离子物质参与溶质-固定相相互作用，由带负电的部分表示，除了亲脂性反映的分配机制之外。碱性药物的质子化虽然不太重要，但也可能影响保留，导致 HSA 表面分配减少，作为净效应，而它似乎对 HSA 结合没有影响。上述结果通过线性溶剂化能关系（LSER）进一步得到证实。 (C) 2010 Elsevier B.V. 保留所有权利。
The retention behavior of 39 structurally diverse neutral, basic and acidic drugs was investigated on an HSA stationary phase using PBS buffer (pH 7.0) and acetonitrile or 2-propanol as organic modifiers. Extrapolated or directly measured log k(w) values as well as isocratic retention factors were correlated with plasma protein binding data taken from the literature. Retention factors determined in the presence of 10% acetonitrile led to high quality 1:1 correlation with apparent log K-HSA values. The derived reference equation was successfully validated using a secondary set of 24 drugs. Further analysis of HSA retention into more fundamental properties revealed the involvement of anionic species in solute-stationary phase interactions, expressed by the negatively charged fraction, besides the partitioning mechanism which was reflected by lipophilicity. Protonation of basic drugs, although less important, may also influence retention, leading to reduced partitioning into the HSA surface as a net effect, while it seems to have no effect on HSA binding. The above results were further confirmed by linear solvation energy relationships (LSER). (C) 2010 Elsevier B.V. All rights reserved.