Laboratory of Separation and Reaction Engineering, Associate Laboratory LSRE/LCM, School of Technology and Management, Polytechnic Institute of Bragança, Campus de Santa Apolónia, Apartado 1134, 5301-857 Bragança, Portugal.
Chirality. 2013 Mar;25(3):197-205. doi: 10.1002/chir.22132. Epub 2013 Jan 21.
The separation of the four nadolol stereoisomers on Chiralpak® AD by chiral liquid chromatography was carried out at both analytical and preparative scales. A screening of possible mobile-phase compositions was performed using different alcohol-hydrocarbon mixtures. The results obtained confirm the use of 20:80:0.3 ethanol-hexane-diethylamine reported by McCarthy (1994) but introduce other possibilities for the complete resolution of the four nadolol stereoisomers at analytical scale, namely, the mixtures 30-40:70-60:0.3 ethanol-heptane-diethylamine. Additionally, this work describes how retention and resolution depend on the ethanol content in hexane and heptane mixtures. The separation of nadolol stereoisomers is also carried out at preparative scale and different alcohol-hydrocarbon compositions are proposed, depending on the target component to be obtained. Particularly, this work presents the experimental separation of the more retained nadolol stereoisomer (RSR-nadolol) by simulated moving bed (SMB) chromatography using an 80:20:0.3 ethanol-heptane-diethylamine mobile phase. For a 2 g/l feed concentration, RSR-nadolol is 100% recovered at the extract outlet stream, 100% pure, and with a system productivity of 0.65 g(RSR-nadolol)/(l(bed)(.)h) and a solvent consumption of 9.6 l(solvent)/g(RSR-nadolol).
手性帕克® AD 对纳多洛尔对映异构体的拆分分别在分析和制备规模上进行。通过不同的醇-烃混合物对可能的流动相组成进行了筛选。所得结果证实了 McCarthy（1994 年）报道的 20:80:0.3 乙醇-己烷-二乙胺的使用，但在分析规模上为完全拆分四个纳多洛尔对映异构体引入了其他可能性，即 30-40:70-60:0.3 乙醇-庚烷-二乙胺混合物。此外，这项工作描述了保留和分辨率如何取决于乙醇在己烷和庚烷混合物中的含量。纳多洛尔对映异构体的分离也在制备规模上进行，并根据要获得的目标成分提出了不同的醇-烃组成。特别是，这项工作通过模拟移动床（SMB）色谱法使用 80:20:0.3 乙醇-庚烷-二乙胺流动相展示了更保留的纳多洛尔对映异构体（RSR-纳多洛尔）的实验分离。对于 2 g/l 的进料浓度，RSR-纳多洛尔在萃取出口流中 100%回收，100%纯，系统产率为 0.65 g(RSR-nadolol)/(l(bed)(.)h)，溶剂消耗为 9.6 l(solvent)/g(RSR-nadolol)。
