March 3–6, 2008, PITTCON® 2008, New Orleans, LA, USA

Efficient Development of Chiral Chromatographic Methods

Teresa Ponzio, Michael McBrien

Abstract

The development of separations for enantiomers remains a considerable challenge in the world of biologically-relevant chemistry. Chromatographers must develop methods for separations on both the analytical and preparative scale. A complication in this process is the fact that it can be quite challenging to predict the system of choice for a given molecule. On the other hand, once a system has been found that shows selectivity between the molecules of interest, optimization is a relatively facile process. Chromatographers have generally taken the approach of screening a considerable number of orthogonal systems to locate an optimizable system for separation. Many injections are performed, and the chromatograms are reviewed to locate the system that is most favorable for optimization. Typical review systems, however, can be inefficient. The onus is on the chromatographer to manually review each chromatogram, sometimes amounting to hundreds of datafiles per day. This process is of course time-consuming. Equally disappointing, typically all of the results of the screens, positive and negative, are discarded. The loss of this considerable knowledge is especially disappointing in light of the fact that many of these molecules will remain active in the organization for some time after the separation is developed. There is an excellent chance that screens will have to be performed again at a later point in the life of the molecule. Recently, systems have been designed to increase the efficiency of chiral screening, while preserving the knowledge gained for retrieval within the organization. These systems work through the connection of multiple data systems, automatically linking sample data with chromatographic and structural information, and providing a streamlined interface for chromatogram review. All of the selectivities measured are automatically stored within a searchable knowledgebase.

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Relevant Products: ACD/Workflow Manager, ACD/ChromManager, ACD/Automation Server, ACD/Web Librarian

Relevant Solution: Chiral Medicinal Chemistry