ABSTRACT
On-column solvent exchange, using many of the principles of solid-phase extraction, has been implemented to significantly reduce evaporation cycle time following reverse-phase preparative HPLC. Additional benefits, such as a reduced potential for salt formation, thermal decomposition, and residual solvent, are also described. Fractions obtained from preparative separations, typically in a large volume of acetonitrile:water, are injected into the preparative HPLC and then eluted in acetonitrile, creating a new fraction in a volatile organic solvent. Minimal modification to the instrument was required, and unattended operation is possible. Acetonitrile evaporation is achieved within 3 h, compared with 17 h for aqueous-based fractions; lower temperatures can be used during the evaporation step; mobile-phase additives, likely to form salts with the target compound if concentrated in the fraction, are removed before evaporation; sample recovery and purity are unaffected.
Subject(s)
Acetonitriles/chemistry , Chromatography, High Pressure Liquid/methods , Solvents/chemistry , VolatilizationABSTRACT
In this Section, we review the applications of mass spectrometry for the analysis and purification of new chemical entities (NCEs) for pharmaceutical discovery. Since the speed of synthesis of NCEs has dramatically increased over the last few years, new high throughput analytical techniques have been developed to keep pace with the synthetic developments. In this Section, we review both novel, as well as modifications of commonly used mass spectrometry techniques that have helped increase the speed of the analytical process. Part of the review is devoted to the purification of NCEs, which has undergone significant development in recent years, and the close integral association between characterization and purification to drive high throughput operations. At the end of the Section, we review potential future directions based on promising and exciting new developments.
