Can reversed-phase flash chromatography purify better than normal-phase?

The answer to this question is yes, reversed-phase can sometimes provide a better separation and thus better purification than normal-phase.  When is reversed-phase likely to be the better choice is a different, and likely better, question.

In this post I will try to demonstrate when reversed-phase is likely the better purification mode.

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How can I reduce flash column purification time and cost?

This is a question being asked of my colleagues and me more and more frequently, especially in pharma accounts.  Why?  Well, you are familiar with the adage – Time is Money, right.  Well this really applies to them. A new molecular entity (NME) created as a pharmaceutical can take up to a decade and a billion dollars to bring to market.  Granted, the biggest costs are in the clinical trials but the synthetic route and the time to discover and make the compound – and purify it – plays a major role within drug discovery and development. This timeline is not helped by the ever increasingly difficult-to-synthesize compounds being investigated as drug candidates today.

With that in mind, this post focuses on ways to speed the purification process without sacrificing purity and yield. Continue reading How can I reduce flash column purification time and cost?

Flash column chromatography equilibration speed – how fast can you go?

Equilibrating silica flash chromatography columns is something I always do.  There are chemists who see this as an unnecessary, time-and-solvent-wasting step.  Because getting consistent, predictable results is a priority, I equilibrate to remove the variability that can be caused by heat generated as solvent initially contacts the silica. Consistency is really important when running flash column chromatography because re-runs are time consuming and may put your compound at risk.

In this post, I examine the role of equilibration speed and duration to show its impact, or lack there of, on purification performance.

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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. 

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