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药物化合物及其对映异构体在复杂样品中胶束电动毛细管色谱法的优缺点:水力开启和封闭系统的比较。

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems.

机构信息

Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina CH2, Ilkovičova 6, SK-84215 Bratislava, Slovakia.

Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria.

出版信息

Int J Mol Sci. 2020 Sep 18;21(18):6852. doi: 10.3390/ijms21186852.

Abstract

Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.

摘要

一些研究学科需要快速、可靠和高度自动化地测定复杂生物基质中的药物活性化合物及其对映异构体。为了解决毛细管电泳(CE)的一些挑战,如浓度灵敏度低以及与基质成分的吸附和干扰相关的性能下降,使用模型化合物普萘洛尔和心得安评估了在水力封闭系统中的 CE。使用一些已建立的验证参数,如注入效率、分辨率和灵敏度的重复性来评估其性能,发现其性能与水力开放系统基本相同。虽然观察到分离效率略有降低,但这主要是由于注入引起的分散所致,即使在掺入复杂生物基质(如血清)中时,也不会影响分辨模型化合物对映异构体的能力。由于使用了大口径毛细管,浓度灵敏度提高了约 18 至 23 倍。这使 CE 的灵敏度达到与液相色谱技术相似的水平。除了这种优势外,与水力开放系统不同的是,电渗流的抑制对于水力封闭系统是必不可少的,它实际上消除了与蛋白质吸附相关的基质效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5571/7555747/97465510de66/ijms-21-06852-g001.jpg

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