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?

Ionizable compound purification using reversed-phase flash column chromatography

With most chromatographic purifications, only two solvents are needed to adequately separate compounds from each other. Unfortunately, there are instances where the separation is either poor or cannot be accomplished with “normal” elution conditions such as those with ionic or very polar organic molecules.

In this post I offer some solutions to this issue.

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Using pH to optimize reversed-phase flash chromatography separations

I have previously posted on the topic of normal-phase optimization by evaluating different solvent blends or mixtures. I have also touched on reversed-phase method development as well suggesting chemists use HPLC to optimize their purification.

In this post, I will look at the impact modifying mobile phase pH can have on reversed-phase separations.

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How do I remove an annoying MS TIC background?

Have you ever run flash column chromatography with mass detection (Flash-MS) and observed the total ion current or TIC increase during the purification only to find that there was no discernible compound contributing to the effect?

In this post I discuss how I came across this issue and the solution I found to work.

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Why is my UV baseline changing during flash column chromatography?

A baseline that rises or drops when using flash chromatography with a UV detector can be a problem, especially if you are trying to collect compounds with poor detectability or that exist in low quantities.

In this post I will talk about the causes and solutions for a rising (or even dropping) baseline. Continue reading Why is my UV baseline changing during flash column chromatography?