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

Higher performance flash columns 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.

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