When should I use a “high-performance” flash chromatography column?

The evolution of flash column chromatography has brought chemists many new and exciting options for crude mixture purification. Among them are so-called high-performance flash columns or cartridges.  These high-performance purification tools are typically filled with silica or other media 15 to 30 microns in particle diameter (versus 40-63 micron for standard flash media) and provide the expectation of better separations and higher purity fractions.  That’s really enticing but how often do you need these types of columns especially since they are, of course, more expensive?  Well, that question is what I address below.

Flash purification, aka flash chromatography, is an off-shoot of organic synthesis. It is an integral part of most synthetic or natural product workflows.  As such, it requires goal setting just as your synthesis project does.  How much final product do I need?  How pure does it need to be?  How fast do I need to develop my synthesis methodology?  Will this need scale-up?  These questions also apply to your purification.

From my perspective, if you are creating or isolating a new molecule it is because it has never been synthesized or it is too expensive to purchase. That being the case then, the compound you are making (including intermediates) or isolating is likely more valuable than any of the reagents and tools you are using – including your flash column.  So, doesn’t it make sense to use the best tool for the job especially if the flash cartridge will provide you with a higher purity compound/intermediate? Why throw away more valuable material that does not meet your purity threshold than you need to?

But does that mean you always need to use high-performance flash columns?  No.  If your separation is easy with a large delta CV (ΔCV) between your targeted compound and its nearest eluting neighbors then a standard particle size media cartridge is fine.  However, that situation is rare and complicated with the desire by most researchers to reduce solvent consumption.  The latter can often be addressed by using the high-performance flash column.  Loading capacity on these superior materials can be 2 to 4 times higher than the standard grade media.  This means smaller column sizes using much less solvent (and less time) can be used effectively without purity sacrifice, Figure 1.

Though the SNAP Ultra cartridge contains 60% less silica it larger surface area and smaller particle diameter increase its loading capacity to be on par with the larger 25 gram KP-Sil cartridghe
Figure 1. Purification performance comparison between a standard 40-63 micron silica, 25 gram flash cartridge (top) and a high-performance 25 micron silica, 10 gram cartridge (bottom).  The amount of crude material loaded was 400 mg on each cartridge.  The high-performance cartridge (bottom) provided a better separation with 60% less silica than the standard silica cartridge and consumed 50% less solvent.

If you invest in your research wisely, including high-performance purification columns, you will surely be rewarded with higher purity final compounds and lower purification costs.

What has your experience been with high-performance flash columns?

Published by

Bob Bickler

Technical Specialist, Biotage

2 thoughts on “When should I use a “high-performance” flash chromatography column?”

  1. Hi Bob!

    I want to ask you a question, but not really coresponding to the topic…
    How do you think, if I want to run reversed-phase column and use a dry load method, can I use an ordinary silica (not C18)? Or it has to be tested and may not work at all?

    1. Hi Vladislav,

      I have done this with success with only a few neutral samples. In theory this can work as the polar mobile phase solvents should rapidly desorb most compounds. However, you may want to test for compatibility as amines and other basic compounds may not desorb well. This problem with organic amines is the reason reversed-phase chromatography was developed!

      Bob

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