June 15-20, 2003, Nice, France, HPLC

ACD/ChromManager as a Tool to Expedite Method Development for Separation of Chiral Molecules by HPLC

Vera Leshchinskaya, Larry. M. Miller, Mike McBrien*, David Powers*
Pfizer, 4901 Searle Pkwy, Skokie, IL USA
*Advanced Chemistry Development
110 Yonge Street, 14th floor
Toronto, Ontario, Canada, M5C 1T4

Abstract

The stereochemistry of organic compounds can have a dramatic effect on their properties, therefore the direct separation of chiral substances by HPLC has had a great impact on the pharmaceutical industry as well as the agrochemical and chemical industries. A large number of pharmaceuticals are most effective as single enantiomers, while the opposite enantiomers often possess an adverse effect. An almost infinite number of chiral compounds exist and over 100 types of chiral stationary phases (CSP) are available. Therefore solutions often are the results of an individual's chromatographic experience and/or screening of a number of CSP. Evaluating multiple CSPs can be time-consuming and sometimes ineffective. A database that allows fast substructure/structure similarity search can use a knowledge base of previous successes to help to find the best solution in the shortest time. This paper will present the design of ACD/ChromManager Database, and the theory and implementation of structure similarity versus substructure searching will be discussed. The search procedure and the logic of method development are also described.