Zeng Lu, Xu Rongda, Laskar Derek B, Kassel Daniel B
Takeda San Diego, Inc., 10410 Science Center Drive, San Diego, CA 92121, USA.
J Chromatogr A. 2007 Oct 26;1169(1-2):193-204. doi: 10.1016/j.chroma.2007.08.079. Epub 2007 Sep 8.
An automated parallel four-column supercritical fluid chromatography (SFC)/MS system to perform high-throughput enantioselective chromatographic method development and optimization is described in this paper. The initial screening was performed in parallel on four chiral SFC columns over several buffer conditions. Optimization of the separation of enantiomers was achieved on a single chiral column. The screening and optimization were accomplished in a fully automated, user-independent manner. Incorporation of column control valves in front of each chiral column allowed the system to switch from parallel four-column screening mode to single-column optimization mode. To facilitate the process, a custom software program, we termed, intelligent parallel optimization for chiral SFC separation (IPOCSS), was developed in-house. The custom software monitored each of the runs in real-time, processed each data set, and by incorporating user-defined criteria (e.g., resolution of the two enantiomer chromatographic peaks), selected the next set of experiments and automatically optimized the enantioseparation. This new approach, combining parallel SFC/MS screening and intelligent software-controlled method optimization, has resulted in a streamlined, high-throughput tool for enantioselective method development, which has been applied successfully to enantioseparations in support of drug discovery.
本文介绍了一种用于高通量对映体选择性色谱方法开发和优化的自动化平行四柱超临界流体色谱(SFC)/质谱系统。初始筛选在几种缓冲条件下,在四根手性SFC柱上并行进行。对映体分离的优化在一根手性柱上完成。筛选和优化以完全自动化、无需用户干预的方式完成。在每根手性柱前安装柱控制阀,使系统能够从平行四柱筛选模式切换到单柱优化模式。为便于操作,我们自行开发了一个定制软件程序,称为手性SFC分离智能平行优化(IPOCSS)。该定制软件实时监测每次运行,处理每个数据集,并通过纳入用户定义的标准(例如,两个对映体色谱峰的分离度),选择下一组实验并自动优化对映体分离。这种结合平行SFC/MS筛选和智能软件控制方法优化的新方法,产生了一种用于对映体选择性方法开发的简化、高通量工具,已成功应用于支持药物发现的对映体分离。