How can I perform normal-phase and reversed-phase column chromatography on one flash system?

For chemists, flash chromatography is part of their everyday synthesis workflow. For most syntheses, crude reaction mixtures are purified by normal-phase (aka adsorption) chromatography.  There are times; however, where the crude mixture’s complexity and polarity make normal-phase chromatography very challenging.  For these situations, reversed-phase (aka partition) chromatography may be a preferred option.

But, if you have only one flash system available, can you, should you, and how do you efficiently switch from non-polar, normal-phase solvents to polar, reversed-phase solvents – and back again without issues? In this post I’ll attempt to shed some light on the topic. 

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Published by

Bob Bickler

Technical Specialist, Biotage

2 thoughts on “How can I perform normal-phase and reversed-phase column chromatography on one flash system?”

  1. Hello Bob

    I am lucky to have a permanent reverse phase system close by. A couple of years ago I had to convert manually from normal phase to reverse phase then back to normal phase which was the default and most popular option. Our machines are shared and people didn’t like having to wait, also worried that there could be water lurking somewhere in the lines. I used ethanol as single intermediate solvent, all four solvents were soluble in ethanol. I guess ethanol is a bit expensive though! I’ve always wondered what would happen if someone pumped a large volume of hexane onto a C18 column by mistake, how long would it take to rescue the column, maybe have to use non-aqueous reverse phase solvents such as acetonitrile/dichloromethane.

    1. Hi Derek,

      Until we launched the Selekt system our NP-RP changeover protocol was 100% NP polar solvent (50 mL), followed by 100% RP organic solvent (50 mL), and finally 100% water (50 mL). Just the opposite to return to NP.

      Hexane on a RP column will not be an issue unless it is stored in it. I have cleaned RP columns with EtOAc, DCM, and hexane and have brought them back to MeOH/water without issue.

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