Strategies for Improving Chromatographic Resolution

Modern drug candidates amongst other compounds present many challenges chromatographically, be that detection, resolution from a co-eluting impurity but one of the most common difficulties faced is the retention and resolution of polar compounds not amenable to typical C18 reversed phase conditions.

Many traditional reversed phase HPLC stationary phases do not provide adequate retention for many of the ever increasing number of polar compounds analyzed by HPLC. These compounds are often unretained in the void volume of the column or retention is so poor their peak shape is compromised or there is co-elution with other poorly retained peaks. Early eluting peaks also elute in an ion-suppression zone which is particular problem for people using LC-MS instruments.

This presentation will summarize the different approaches available outside of normal phase chromatography which is generally avoided by most labs due to poor robustness, incompatible solvents – especially for LC-MS and also the lack of efficiency with normal phase methods.