仿生色谱——色谱原理的新应用

IF 3 Q2 CHEMISTRY, ANALYTICAL
Klara L Valko
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引用次数: 5

摘要

仿生色谱是高效液相色谱(HPLC)方法的名称,该方法使用含有蛋白质和磷脂的固定相,可以模拟药物分子分布的生物环境。所应用的流动相为pH值为7.4的有机水相,以模拟人体中可能遇到的生理条件。分子在仿生固定相上的校准保留揭示了化合物对蛋白质和磷脂的亲和力,这可以用来模拟分子的生物和环境命运。该技术标准化后,能够预测化合物在体内的分配和分布行为,并有助于选择最佳化合物进行进一步研究,以成为药物分子。应用仿生色谱测量有助于减少药物发现过程中动物实验的数量。新的仿生固定相,如鞘磷脂和磷脂酰乙醇胺,扩大了在血脑屏障分布和肺组织结合建模中的应用。最近,测量的性质也被用于预测毒性,如磷脂中毒和心脏毒性。利用仿生色谱数据可以预测药物和农药的水生毒性。仿生色谱分离方法也可以在未来扩展到预测蛋白质和受体结合动力学。新的仿生固定相和新的预测模型的发展将进一步加速该分析方法的广泛应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biomimetic chromatography—A novel application of the chromatographic principles

Biomimetic chromatography—A novel application of the chromatographic principles

Biomimetic chromatography is the name of the High Performance Liquid Chromatography (HPLC) methods that apply stationary phases containing proteins and phospholipids that can mimic the biological environment where drug molecules distribute. The applied mobile phases are aqueous organic with a pH of 7.4 to imitate physiological conditions that would be encountered in the human body. The calibrated retention of molecules on biomimetic stationary phases reveals a compound's affinity to proteins and phospholipids, which can be used to model the biological and environmental fate of molecules. This technology, when standardised, enables the prediction of in vivo partition and distribution behaviour of compounds and aids the selection of the best compounds for further studies to become a drug molecule. Applying biomimetic chromatographic measurements helps reduce the number of animal experiments during the drug discovery process. New biomimetic stationary phases, such as sphingomyelin and phosphatidylethanolamine, widen the application to the modelling of blood–brain barrier distribution and lung tissue binding. Recently, the measured properties have also been used to predict toxicity, such as phospholipidosis and cardiotoxicity. The aquatic toxicity of drugs and pesticides can be predicted using biomimetic chromatographic data. Biomimetic chromatographic separation methods may also be extended in the future to predict protein and receptor binding kinetics. The development of new biomimetic stationary phases and new prediction models will further accelerate the widespread application of this analytical method.

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