Yan Tony Q, Orihuela Carlos, Swanson David
Amgen, Inc., Amgen One Center Dr., Thousand Oaks, California 91320, USA.
Chirality. 2008 Feb;20(2):139-46. doi: 10.1002/chir.20512.
This article discusses the chromatographic resolution of a racemic pharmaceutical intermediate. Preparative batch high performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), steady-state recycling (SSR), and simulated moving bed (SMB) were used to resolve a total of 12.2 kg of a racemic pharmaceutical intermediate. In this study, a first batch of 0.8 kg of racemate was separated on the preparative batch HPLC and SFC, and subsequently another 5.9 kg of racemate was separated on the SSR. Lastly, a third batch of 5.5 kg was separated on the SMB. The separation conditions and results of these techniques are discussed. The productivities and solvent costs of SFC versus HPLC are compared. The productivities and solvent costs of SMB, SSR, and HPLC are also compared. The analytical method development and process optimization of these processes are also discussed in this article.
本文讨论了一种外消旋药物中间体的色谱拆分。采用制备间歇高效液相色谱（HPLC）、超临界流体色谱（SFC）、稳态循环（SSR）和模拟移动床（SMB）共拆分了12.2千克外消旋药物中间体。在本研究中，第一批0.8千克外消旋体在制备间歇HPLC和SFC上进行分离，随后又有5.9千克外消旋体在SSR上进行分离。最后，第三批5.5千克在SMB上进行分离。讨论了这些技术的分离条件和结果。比较了SFC与HPLC的生产率和溶剂成本。还比较了SMB、SSR和HPLC的生产率和溶剂成本。本文还讨论了这些工艺的分析方法开发和工艺优化。
