How Much Is My Flash Chromatography System Really Going to Cost?

This, of course, is always one of the first questions an organic, medicinal, or peptide chemist has when starting the research process for a flash chromatography system. Here at Biotage, we receive this question hundreds and hundreds of times a year, likely within the first couple of minutes of any conversation.

To learn how to break down the cost, click here.

Organic Chemistry Workflow – Typical Steps and Equipment

Synthetic organic chemistry is the genesis of new pharmaceutical and commercial chemical products. In short, it is based on the idea that two or more carbon-based compounds can be forced to react using heat, or other energy source, to create a new, novel product – but this we already know.

To learn more about the workflow, click here!

How important is your flash column’s plate count, aka efficiency, to your purification?

Plate count is a theoretical number describing the separation efficiency of a chromatography column. In short, it is a measure an eluting compound’s bandwidth at the time it elutes from a column, Equation 1….

Find out what Equation 1 is here!

Prep HPLC vs. reversed-phase flash chromatography: How to choose?

This question is one that is increasing in frequency. Over the past 10 or so years reversed-phase flash chromatography use has increased dramatically. Likewise, reversed-phase preparative HPLC (RP pHPLC) use has also increased. Chemists need to know when to choose between the speed and low solvent use of flash column chromatography and the ultimate purification of RP pHPLC. With this as the backdrop, let me give you my thoughts on hot to choose between flash chromatography and when it is best to use RP pHPLC.

 

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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.

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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. 

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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.

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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.
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