Welcome to the Biotage Flash Purification Blogs.

      Flash column equilibration – is it a waste of time or necessary step?

      November 1, 2019 at 9:30 PM / by Bob Bickler posted in Optimization, Media, Theory

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      slash column chromatography has been practiced by chemists since the 1970s. That practice requires the silica in the column be properly wetted to remove trapped gasses and ensure uniform flow (remember those days of not letting air into the column?). Today, with automated flash chromatography systems and pre-packed columns as the norm, chemists ask me – do I really need to pre-equilibrate my column?

      In this post I explore the impact on chromatography that equilibration, and lack thereof, has on separation performance.

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

      October 29, 2019 at 5:00 PM / by Bob Bickler posted in Optimization, Media

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      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.

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      Biotage vs Biotage, and the winner is...

      October 23, 2019 at 9:28 AM / by Panagiotis Ioannidis posted in Chromatography, Optimization

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      When Isolera™ was launched, the maximum system pressure that could be reached was 10 bars, but reaching that pressure was a challenge since most of the Flash columns could not withstand the higher pressures. The maximum pressure rating for the Biotage® SNAP columns, for example, is limited to five or seven bars, depending on the size, and columns from most of manufacturers have the same limitation.

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      Six key factors that impact flash chromatography

      October 18, 2019 at 9:54 PM / by Bob Bickler posted in Optimization, Solvents, Media

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      In this post I will delve into six key factors that impact your purification success in flash column chromatography.

      Previously, I have discussed the use of TLC for solvent scouting and method development and optimization. I have have also talked about cartridge size, particle size, and surface area and their impact on flash purification.  Here I integrate that information into the six factors below.

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      How do I purify my high boiling solvent reaction mixture using silica flash chromatography?

      October 18, 2019 at 9:48 PM / by Bob Bickler posted in Optimization, Solvents

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      Many chemists today find they need to synthesize molecules at higher temperatures in order to force difficult reactions to proceed. Solvents such as DMF, DMSO, and NMP are commonly used in these reactions as they facilitate the use of the high reaction temperatures.  However, the same attributes that make these chemicals attractive as reaction solvents make compound recovery from them very difficult, including flash column chromatography.  These high boiling solvents are typically polar and pose a challenge if purification is to be accomplished with normal-phase silica.

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

      October 4, 2019 at 6:30 PM / by Bob Bickler posted in Cannabis, Chromatography, Gradient, Normal phase, Optimization, SNAP, Solvents, Troubleshooting, Selekt, Media, Mass-directed purification, Theory

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      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. 

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      What is a Chromatography Gradient?

      October 2, 2019 at 3:27 PM / by Bob Bickler posted in Gradient, Optimization

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      Gradients, used in chromatographic methods, assist with chemical separation and elution. They begin with “weak” elution conditions and end with “strong” elution conditions.

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      Using TLC to Scout Flash Chromatography Solvents

      September 20, 2019 at 3:06 PM / by Bob Bickler posted in Optimization, Solvents, TLC, Theory

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      TLC is the tool most used for normal-phase flash chromatography method development. For many chemists, a solvent system of hexane (or heptane) + ethyl acetate is the first, and sometimes only, solvent system evaluated. Though often useful, ethyl acetate may not always provide the optimal purification conditions.

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      How do I Create an Efficient Gradient Flash Chromatography Method?

      September 20, 2019 at 2:58 PM / by Bob Bickler posted in Gradient, Optimization

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      For most organic and medicinal chemists flash chromatography is just another step in the synthesis work flow - react, analyze, purify, react, analyze, purify... until the final product is made. The desired product of each reaction, and the mixture of other species present are, of course, different with each cycle.  Separating the desired compound efficiently without a lot of hassle is something I have written about in this post as well as in others in this series.

      In this post, I've written about how that TLC (thin layer chromatography) plate you use for monitoring your reaction can be used to create reliable, efficient, effective gradients.

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      What is Flash Chromatography and why should I do it?

      August 20, 2019 at 5:34 PM / by Bob Bickler posted in Optimization

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      Flash chromatography is a chemical separation technique used to purify chemical mixtures. Because it is a purification technology, the process is also referred to as flash purification.

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      How to minimize particulate build-up in flash chromatography systems

      July 9, 2019 at 3:23 PM / by Bob Bickler posted in Optimization, Media

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      In order to perform flash chromatography consistently, the equipment you use must be properly maintained by following some “best practices”. These best practices include using clean solvents (I typically use ACS grade), volatile organic modifiers, and quality columns.

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      How changing stationary phase chemistry can impact separation selectivity

      June 12, 2019 at 2:42 AM / by Bob Bickler posted in Optimization, Media

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      Challenging separations, we all have faced this vexing problem. You synthesized your compound, analyzed it, and know your molecule is in there, based on LC-MS or TLC. Then, you do some method development using a silica TLC plate and see a major spot with some minor, early-eluting impurities. You think that the purification will be easy only to find that your “purified” compound has some co-eluting impurities. Now what? Should you change solvents or change stationary phase?

      In this post, I will show how changing the column media but keeping the same solvents removed a co-eluting impurity in one of my reaction mixes.

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      Minor Cannabinoid Separation by Reversed-phase Flash Chromatography

      May 17, 2019 at 8:30 PM / by Bob Bickler posted in Cannabis, Chromatography, Optimization, Reversed-phase

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      Previously, I have posted on a normal-phase flash chromatography method to separate and isolate CBG from a CBD-rich hemp distillate. CBG is just one of many naturally occurring minor cannabinoids of interest in this fast-growing market.

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      How can I reduce flash column purification time and cost?

      May 8, 2019 at 2:57 PM / by Bob Bickler posted in Optimization

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      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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      Determining solvent strength in flash column chromatography

      May 7, 2019 at 5:23 PM / by Bob Bickler posted in Optimization, Solvents

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      Recently, one of our readers wrote and asked how to determine solvent strength in normal-phase flash chromatography. This is an excellent question because solvent strength is one of several factors impacting flash chromatography performance.

      In this post I will explain how solvent strength can easily be determined.

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      Isolation of some minor cannabinoids using flash chromatography

      April 16, 2019 at 11:02 PM / by Bob Bickler posted in Cannabis, Optimization

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      Cannabis entrepreneurs continually seek to differentiate themselves from others in the market. Some focus on THC while others focus on CBD. What I have seen recently after attending some cannabis-specific conferences is a growing interest in isolating/purifying some of the minor, naturally occurring phytocannabinoids such as CBG and CBDV.

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