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仿生色谱法——色谱原理的一种新应用。

Biomimetic chromatography-A novel application of the chromatographic principles.

作者信息

Valko Klara L

机构信息

UCL School of Pharmacy Bio-Mimetic Chromatography Ltd BTC Bessemer Drive Stevenage UK.

出版信息

Anal Sci Adv. 2022 Apr 11;3(3-4):146-153. doi: 10.1002/ansa.202200004. eCollection 2022 Apr.

Abstract

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.

摘要

仿生色谱法是高效液相色谱(HPLC)方法的一种,它采用含有蛋白质和磷脂的固定相,这些固定相能够模拟药物分子分布的生物环境。所应用的流动相是pH值为7.4的水相有机相,以模拟人体中会遇到的生理条件。分子在仿生固定相上的校准保留率揭示了化合物对蛋白质和磷脂的亲和力,这可用于模拟分子的生物和环境归宿。这项技术标准化后,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的动物实验数量。新型仿生固定相,如鞘磷脂和磷脂酰乙醇胺,拓宽了其在血脑屏障分布建模和肺组织结合方面的应用。最近,所测得的性质也已用于预测毒性,如磷脂沉积症和心脏毒性。药物和农药的水生毒性可以利用仿生色谱数据进行预测。未来,仿生色谱分离方法可能还会扩展到预测蛋白质和受体结合动力学。新型仿生固定相和新预测模型的开发将进一步加速这种分析方法的广泛应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f6a/10989578/bfd6e1c2da50/ANSA-3-146-g001.jpg

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