HPLC HINTS & TIPS for Chromatographers
Tip# 104: CHIRAL HPLC / SFC METHOD DEVELOPMENT (Alcohol's):
We are experts in chiral HPLC and SFC method development of pharmaceutical samples and have operated a contract separations labs for nearly two decades. We have learned a great deal about developing fast and reliable racemate separation methods, often where other companies have failed. The knowledge we have gained has allowed us to develop over ten thousand new chromatographic methods for our clients. This has made our company the leading consulting expert in the chiral field.
I would like to share a tip with you regarding the use of different alcohol's in chiral method development. That tip is to experiment with different alcohol's 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 alcohol's to achieve excellent separations. These alcohol's are often used isocratically at 100% concentration for HPLC methods and at levels ~ 15 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). For SFC methods, Methanol, Ethanol and Butanol (plus mixtures of these) are still some of our favorite co-solvents.
Here is a list of some popular alcohol's (HPLC grade) worth using in your chiral method development:
Methanol; Ethanol;1-Butanol; 2-Propanol; 2-Butanol and Acetonitrile (I know this is not an alcohol, but it is often overlooked in chiral method development. It works where other solvent systems fail for both HPLC (100%) and less so for SFC (10% as a co-solvent with Methanol).
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. > Bill Letter,
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