It is not realistic to predict an appropriate chiral separation method just by looking at analyte structure however, some limiting decisions can be made.Basic automation of method development involves selecting a reasonable set of columns and eluents for the analytes expected.Automation software and hardware then sequentially exposes each analyte to a set of methods optimized for screening each eluent against all appropriate and available columns.If an HPLC/SFC system is configured with a polarimeter it is easy to positively identify enantiomerically pure separations.Gradient methods are best for screening because a single injection is exposed to more eluent variation in less time and a gradient can often be designed to wash the column near the end of each run.
Techniques for chiral prep purifications are roughly divided at the one kilogram of racemate level.Above one kilogram processes and systems tend to be well researched and optimized for low solvent consumption and low total cost.Simulated moving bed (SMB) type systems dominate this region.Below one kilogram processes tend to be optimized for quick turn-around and system flexibility.HPLC is the traditional choice but SFC is proving to have an advantage over HPLC because there is less liquid to be evaporated after collection.
The majority of small molecule pharmaceutical candidates are chiral compounds containing one or more chiral centers.Polarimeters are very useful in many applications during development and production of these compounds.They can be used to properly identify chiral peaks among a number of UV or MS (mass spectrograph) peaks, quantitate enantiomeric separation and purity, and robustly direct prep fraction collectors in enantiomeric purification.
The large linear dynamic range of modern polarimeters and their ease of operation make them ideal detectors for automated chiral method development and prep purification systems.In method development a polarimeter will confirm enantiomeric separation by showing the characteristic positive and negative enantiomeric peaks.