A simple instrumental approach for 'supercritical' fluid chromatography in drug discovery and its consequences for coupling with mass spectrometric and light scattering detection

In spite of the name supercritical fluid chromatography (SFC), SFC systems are generally operated in the subcritical state. When both the temperature and pressure are below the critical point of the CO(2)-modifier mixture, phase separation may occur, which is claimed to destroy the separation. We show here, however, that working below the critical temperature and pressure has no practical detrimental effect on the separation; its only detrimental effect is on detection by UV. This contribution describes a simple experimental setup applied in recent years in a drug discovery laboratory and illustrates some anomalies and misconceptions about SFC for drug discovery.In spite of the name supercritical fluid chromatography (SFC), SFC systems are generally operated in the subcritical state. When both the temperature and pressure are below the critical point of the CO(2)-modifier mixture, phase separation may occur, which is claimed to destroy the separation. We show here, however, that working below the critical temperature and pressure has no practical detrimental effect on the separation; its only detrimental effect is on detection by UV. This contribution describes a simple experimental setup applied in recent years in a drug discovery laboratory and illustrates some anomalies and misconceptions about SFC for drug discovery.A