HPLC separation strategies for compounds with multiple chiral centers and the practical pharmaceutical considerations

Kelly Zhang, Genentech, South San Francisco, United States (zhang.kelly@gene.com)

With the increasing complexity of pharmaceutical molecules, the availability of pure chiral starting materials and the advances of asymmetric synthesis, there are more and more new drug candidates come with multiple chiral centers. Each of the chiral entity has to been strictly quantified and monitored in order to ensure drug safety and quality. Frequently, multiple methods have to be used in order to characterize the chiral purity of a sample and sometimes even the combination of multiple methods is still not necessarily able to provide the required information.

In this lecture, we will present our fast HPLC method development and sample analysis strategies based on the results of our recent screening studies of compounds with multiple chiral centers. We will present our strategies of fast method development. The impact of different stationary phases including phase chemistry, particle size, noncovalently vs covalently bonded chiral phases will be presented, together with the impact of other factors such as mobile phases, gradient vs isocratic etc. to the separation efficiency. Strategic application of multi-dimensional separation for compounds with multiple chiral centers will be demonstrated. We will also discuss the practical considerations of chiral separation method, sample preparation and analysis for pharmaceutical samples.  

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Abstract Reference & Short Personal Biography of Presenting Author

Dr. Kelly Zhang is a Principal Scientist at Genentech in South San Francisco, California. She leads analytical chemistry R&D teams for drug substance and drug formulation, moving novel therapeutic molecules forward from research to clinical trials through collaboration with cross-disciplinary teams. Her current research interests are chiral separation, multi-dimensional separation, universal detection and high throughput automation. She was named one of the top 50 most influential women in analytical science by The Analytical Scientist. She is a member of the Permanent Scientific Committee of the international HPLC conference series.