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

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?

How do particle size and flow rate affect normal-phase flash column chromatography?

Media particle size and solvent flow rate play major roles in chromatographic separations including flash purification.  This is true in both reversed-phase chromatography (aka partition chromatography) as well as normal-phase chromatography.

The roles played are related to the overall compound mass-transfer kinetics and diffusion/dispersion as they migrate through the column.  Smaller particles reduce sample dilution by reducing interstitial volume, while flow rate impacts the ability of molecules to efficiently pass through the porous particles.

In this post, I will show how both particle size and flow rate impact flash chromatography.

Continue reading How do particle size and flow rate affect normal-phase flash column chromatography?

How can I make purification of hard-to-separate compounds greener?

The planet’s population is growing, its resources are dwindling – this is a problem.  On top of that environmental contamination from myriad sources is only compounding the issue of available clean food and water.

As chemists, we contribute to this issue, to some degree, by performing reactions that generate chemical waste in the form of unwanted by-products and excess solvents from work-up and purification. What can we, as chemists, do to help reduce our so-called “carbon footprint”?

In this post, I discuss some ways to improve flash chromatography resource utilization, especially for hard separations.
Continue reading How can I make purification of hard-to-separate compounds greener?

So, which detector should I use for flash column chromatography?

In my role as senior technical specialist at Biotage I am often asked about compound detection options. For most flash chromatography methods, UV is the default detection tool since a majority of compounds do absorb some UV light.

Diode array UV detectors provide chemists choices in wavelength selection, providing the ability to widen or narrow the wavelength range needed to detect specific compounds and enhance their sensitivity.

When diode array detectors fail to detect compounds, it is because the compounds have no chromophore, e.g. carbohydrates, low extinction coefficients, exist in really low concentrations, or any combination of these.  In these situations, alternative detectors are quite beneficial.  In this post I will discuss a couple of detector options for flash chromatography. 

Continue reading So, which detector should I use for flash column chromatography?

5 Steps to successful flash chromatography

The bane of organic synthesis for most chemists is purification rather than synthesis. Synthetic reaction mixtures are rarely devoid of impurities so some type of purification is necessary.  Most often flash chromatography is used but for many chemists, it is less well understood than their chemical reaction and provides some level of anxiety.

In this post, I will summarize the five most important steps to creating a successful flash chromatography method and thus the anxiety associated with it.

Continue reading 5 Steps to successful flash chromatography

How does solvent choice impact reversed-phase flash chromatography separations?

I have recently posted on how solvent choice influences the separation of hard to resolve compounds using normal-phase flash chromatography. As a chemist with an inquiring mind, I thought I would expand my research beyond normal-phase and see what happens in reversed-phase.

In this post, I share my results. 

Continue reading How does solvent choice impact reversed-phase flash chromatography separations?

How to efficiently scale-up flash column chromatography

For synthesis and medicinal chemists, compounds are typically made only once en route to a final product. Once that compound shows activity toward a particular target, then the synthesis is scaled up meaning that purification too requires scaling. The same is true in natural product research where once a high-value compound is isolated at small scale, there is a need to isolate it at larger scale.

Both of these scenarios can be problematic to scale-up/ process chemists when other, non-chromatographic purification techniques are not successful. When this happens, either a different synthetic route or extraction process is needed or large scale chromatography is employed. In this post, I will explain how flash chromatography can be successfully scaled while minimizing time and solvent consumption. Continue reading How to efficiently scale-up flash column chromatography

How can I rapidly remediate THC from CBD in my hemp extract using flash column chromatography?

Tetrahydrocannabinol, aka THC, is a hallucinogen found in cannabis and, to a lesser degree, in hemp.  Though THC is legal in some locations in the US and Canada, there is a growing market for its non-hallucinogenic cousin, cannabidiol (CBD), which has purported medical benefits.

The problem with isolating CBD from cannabis and hemp is contamination from THC, which is typically present at a moderate to high percentage. In this post, I will provide some insight into rapidly purifying CBD to remove THC. Continue reading How can I rapidly remediate THC from CBD in my hemp extract using flash column chromatography?