How does solvent choice impact flash column chromatography performance?

Selectivity and solvent strength are the most important factors that determine success or failure of a chromatographic separation. These two independent dynamics apply to both normal- and reversed-phase chromatography and should be optimized, especially when high fraction purity is needed.

In this post I will discuss the impact that elution solvent choice has on both normal- and reversed-phase purification.

Read more here!

Published by

Bob Bickler

Technical Specialist, Biotage

3 thoughts on “How does solvent choice impact flash column chromatography performance?”

  1. I’ve tried several times experimenting with solvent blends to achieve different selectivity. But I would say that in the majority of cases I don’t see any significant change in Rf between the spots. For me, this has been slightly discouraging but perhaps it is just bad luck. There is a nice paper that describes the determination of the composition of a binary solvent mixture if a given eluent strength is needed https://doi.org/10.1016/0021-9673(93)80156-3.
    So for example, substituting THF for EtOAc wasn’t very successful for me. It seems that the only time I get useful results is when I try some ‘exotic’ blends.

    1. Very interesting, Tomasz. Are there specific compounds classes you find less affected by solvent composition changes? You mention exotic blends – I would like to know more about these blends and the types of compounds where you have had success. I will also try to read the article for which you provided a link.

      1. Thanks for your reply. I can’t pinpoint any specific class of compounds that would be affected less. Simply anytime when doing scouting TLC I get closely running spots with EtOAc/hexane (my standard blend) I try and substitute EtOAc for something else (THF, acetone, ether, IPA, etc.). I usually observe just the minor alteration in Rf, nothing major that would greatly simplify running a column. Maybe I am expecting too much 🙂
        But I remember one time when I was working with dextromethorphan (morphinan scaffold) derivatives I invested a couple of days to properly develop a method for column purification and after running countless TLC plates I found hexane:tBME 7:3 + 2% TEA (if I remember correctly) to do the trick. No tailing, great selectivity. Doing RP-C18 in ion-pair mode was not an option then (which I reckon would be more straightforward). Normally when dealing with NP silica I stick with two components blends.

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