Does high performance flash column chromatography require high performance TLC for method development?

Higher performance flash cartridges are becoming all the rage these days.   Chemists are using them for challenging as well as for routine purification.   As a result, I am often asked, “do I need high-performance TLC plates for method development?”

In this post I will explain why the answer is no.

TLC is the most commonly used method development tool used with normal-phase flash chromatography.  The reason for this is that a silica TLC plate has selectivity that is similar to silica cartridge selectivity.  This allows for fairly accurate prediction of optimal chromatographic conditions.

Selectivity is the operative word here.  It is the SOLE reason TLC is used for method development.  If two or more compounds separate on TLC, then they should separate using a silica flash column with the same solvent system.  The TLC solvent combination also can be converted to a gradient as well, which will further improve the separation.

It is true that high performance TLC plates provide tighter elution bands and provide better resolution than standard TLC plates but with TLC for flash we are just evaluating different solvent blends and ratios to find the combination that best separates our targeted compound from the other impurities.

Resolution, and therefore sample load, are contingent more on TLC selectivity (ΔCV) than anything else because we do not know how much sample we are applying to the TLC plate (or how much silica is on the plate for that matter).

So, in my opinion, save your money and stay with conventional, standard performance TLC for flash method development; I do.

Have you found high performance TLC plates provided better high-performance flash chromatography method development data? Please share your experiences with us.

Published by

Bob Bickler

Technical Specialist, Biotage

3 thoughts on “Does high performance flash column chromatography require high performance TLC for method development?”

  1. TLC is quick and easy but for a lot of people I work with it’s still too much trouble. If a purification fails with the default gradient then the sample goes to the FractionLynx, then it’s someone else’s problem. Sometimes you have a purification which just has to be done by flash and requires a good result rather the default gradient. eg 100g of crude with close impurities, then you need to do some method development. With TLC you can check out a variety of solvent mixtures in a relatively short time, works well with hexane/EtOAc but not with CH2Cl2/MeOH.
    I’ve used high performance amino, cyano and diol bonded TLC plates but they are too expensive. Don’t know why they can’t be made with lager particles. If they were cheaper then we would be using polar bonded columns routinely for normal phase flash but without TLC plates we can’t check for suitability.

    1. Hi Derek,

      Yes, I encounter the same sentiment quite often regarding TLC use for solvent scouting and method development.
      With regards to the issue of the high-performance bonded-silica plates, I believe this is due to the fact that the main market for TLC is analytical chemistry so smaller particles provide tighter bands, more resolution, and therefore a more complete separation. So, the TLC manufacturers focus on offering the highest performance product to address that market need. For flash, as you know TLC is used to find suitable solvent systems to separate the targeted compound from its impurities/by-products so we really only need to know the Rf values of the target and it nearest eluting neighbors to determine the flash method and sample load.

      Bob

  2. One more implication of that is you don’t have to use necessarily the same source of silica either, ie. Biotage TLC plates for purification on Biotage columns 🙂

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