I would like to share a tip with you regarding the use of different alcohols in chiral method development. That tip is to experiment with different alcohols during the method development process (*Please make sure the alcohol is compatible with your column!). Many of the normal and reversed phase chiral columns can be used with some unconventional alcohols to achieve excellent separations. These alcohols are often used isocratically at 100% concentration for HPLC methods and at levels ~ 10 to 20% for many SFC methods. We have had a great deal of success using 100% pure Methanol for HPLC methods on normal phase style chiral columns (though 100% Ethanol is still one of the best alcohols to initially choose). For SFC methods, Methanol, Ethanol and Butanol (plus mixtures of these) are still some of our favorite co-solvents.Note: SFC needs these alcohols to make the compressed CO2 more polar. Since most chiral drug compounds are resolved using Normal Phase chromatography, SFC is still limited in what it can resolve chromatographically vs HPLC. SFC will never replace conventional HPLC as SFC is far more limited in application (restricted in its range of polarity), but SFC is a worthwhile and important technique to supplement HPLC separations.
- Here is a list of some popular alcohols (HPLC grade) worth using in your chiral method development:
- A note about acids. Weaker is often better in chiral method development. Examples: TFA at 0.01% and Acetic or Formic Acids at 0.1% concentration are often strong enough to ionize most compounds.