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基于三-(3,5-二甲基苯基氨基甲酸酯)纤维素的手性固定相用于超临界流体色谱中药物的对映体分离:与 HPLC 的比较。

Cellulose tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase for the enantioseparation of drugs in supercritical fluid chromatography: comparison with HPLC.

机构信息

Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic.

Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, Austria.

出版信息

J Sep Sci. 2018 Mar;41(6):1471-1478. doi: 10.1002/jssc.201701341. Epub 2018 Jan 26.

Abstract

A cellulose tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase was studied as a tool for the enantioselective separation of 21 selected analytes with different pharmaceutical and physicochemical properties. The enantioseparations were performed using supercritical fluid chromatography. The effect of the mobile phase composition was studied. Four different additives (diethylamine, triethylamine, isopropylamine, and trifluoroacetic acid) and isopropylamine combined with trifluoroacetic acid were tested and their influence on enantioseparation was compared. The influence of two different mobile phase co-solvents (methanol and propan-2-ol) combined with all the additives was also evaluated. The best mobile phase compositions for the separation of the majority of enantiomers were CO /methanol/isopropylamine 80:20:0.1 v/v/v or CO /propan-2-ol/isopropylamine/trifluoroacetic acid 80:20:0.05:0.05 v/v/v/v. The best results were obtained from the group of basic β-blockers. A high-performance liquid chromatography separation system composed of the same stationary phase and mobile phase of similar properties prepared as a mixture of hexane/propan-2-ol/additive 80:20:0.1 v/v/v was considered for comparison. Supercritical fluid chromatography was found to yield better results, i.e. better enantioresolution for shorter analysis times than high-performance liquid chromatography. However, examples of enantiomers better resolved under the optimized conditions in high-performance liquid chromatography were also found.

摘要

一种基于三-(3,5-二甲基苯基氨基甲酸酯)纤维素的手性固定相被研究用于对具有不同药物和物理化学性质的 21 种选定分析物进行对映选择性分离。对映异构体分离是在超临界流体色谱中进行的。研究了流动相组成的影响。测试了四种不同的添加剂(二乙胺、三乙胺、异丙胺和三氟乙酸)以及异丙胺与三氟乙酸的组合,并比较了它们对对映体分离的影响。还评估了两种不同的流动相共溶剂(甲醇和 2-丙醇)与所有添加剂的组合的影响。对于大多数对映异构体的分离,最佳的流动相组成是 CO /甲醇/异丙胺 80:20:0.1 v/v/v 或 CO /2-丙醇/异丙胺/三氟乙酸 80:20:0.05:0.05 v/v/v/v。最佳结果来自碱性β-受体阻滞剂组。考虑了由相同固定相和具有相似性质的流动相组成的高效液相色谱分离系统,流动相为己烷/2-丙醇/添加剂 80:20:0.1 v/v/v。与高效液相色谱相比,超临界流体色谱在较短的分析时间内获得了更好的结果,即更好的对映体分辨率。然而,也发现了在高效液相色谱中在优化条件下更好分离的对映异构体的例子。

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