Welcome to the Biotage Flash Purification Blogs.

    Does size really matter in flash chromatography? Part 1

    January 7, 2020 at 8:43 PM / by Bob Bickler posted in Chromatography Fundamentals, Normal Phase

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    Yes, the title is a bit salacious but it got your attention, didn’t it? I believe this is a topic worthy of discussion as it relates to flash chromatography for purification because many chemists believe longer but thinner columns perform better than short, wide columns.  The facts of the matter may surprise you.

    In this post I discuss the impact that cartridge dimensions have on purification performed using flash purification.

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

    January 3, 2020 at 3:38 PM / by Bob Bickler posted in Reversed-phase, Detector, Normal Phase

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    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 many 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.

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    How do I decide between normal- or reversed-phase flash column chromatography?

    December 30, 2019 at 4:49 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Green, Normal Phase, Isolera, HPLC

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    Choosing a good purification strategy is an important for successful crude compound purification. A major factor in your strategy is choosing between normal-phase or reversed-phase chromatography.  How do you choose?

    In this post, I will provide some simple guidance on helping determine which route to take.

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    Are there advantages to stacking flash chromatography columns?

    December 30, 2019 at 4:38 PM / by Bob Bickler posted in Chromatography Fundamentals, Normal Phase

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    When it comes to isolating a compound from a mixture at maximum purity there are many options available through flash column chromatography. In previous posts I have addressed using smaller particle media, higher surface area media, and step gradients to achieve this goal.

    In this post I will discuss how stacking columns in series may help improve separation quality.

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    Pushing flash column chromatography loading limits

    December 30, 2019 at 3:39 PM / by Bob Bickler posted in Chromatography Fundamentals, Green, Sfär, Loading Techniques, Cost, Normal Phase, Pillar Page

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    A question I hear a lot from chemists is “how much can I load”. The answer is always “it depends on your separation quality”.  At that point I begin asking about the TLC data and purification goals. Purification goal setting should be your first step and the question to answer is – what do I need this purification to achieve? Is the goal high purity, high yield, or some combination.  Remember, you will typically sacrifice purity for high yield and yield for high purity so optimization is an important consideration.

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    Green Flash Chromatography Webinar

    November 26, 2019 at 9:03 PM / by Bob Bickler posted in Green, Sfär, Selekt, Webinar, Cost, Normal Phase

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    Over the past several decades, the chemical industry has implemented process changes and updated practices in R&D and manufacturing in an effort to reduce liquid and solid lab waste. The pharmaceutical industry in particular has taken steps within their drug discovery labs to reduce solvent use by requiring their chemists to find and implement measures that achieve the corporate environmental goals without curtailing their productivity – quite the challenge.

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    Does particle shape and/or particle size impact flash column chromatography load limits?

    November 21, 2019 at 3:51 PM / by Bob Bickler posted in Chromatography Fundamentals, Media and Resin, Normal Phase, Isolera

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    There are many factors which influence successful flash column chromatography. One of those factors is sample load, which itself is influenced by things like selectivity, efficiency, dissolution solvent, and load technique. Several of these factors I have addressed in previous posts. Of these, selectivity and efficiency are specific to a media's physical and chemical characteristics.

    In this post I will show if particle size and/or particle shape can influence loading capacity.  Additionally, I will show the positive impact that surface area has on flash column chromatography purification.

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    Why can’t I reproduce my TLC separation using flash column chromatography?

    November 21, 2019 at 3:48 PM / by Bob Bickler posted in Chromatography Fundamentals, Troubleshooting and Optimization, Normal Phase

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    You have performed your synthesis and now it is time to purify the reaction mix. You have used thin-layer chromatography (TLC) and see a separation but when you try to purify with flash column chromatography, you can’t get the target compound separated from an impurity. So, what is happening (or isn’t happening)?

    In this post I will give some input on why some separations are not transferable from TLC.

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    How does mobile phase organic solvent choice impact reversed-phase flash column chromatography?

    November 21, 2019 at 3:45 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Solvents, Normal Phase, Isolera

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    Organic and medicinal chemists frequently utilize flash chromatography to purify their reaction mixtures. Normal-phase flash chromatography is most often used but may not the best methodology, especially when the compounds are quite polar and/or ionizable.

    For these molecules, reversed-phase flash chromatography is preferred but often is not used due to an uncertainty regarding the best solvent choices and the reversed-phase mechanism.  In this post, I will discuss how organic solvent choice in reversed-phase chromatography can influence the chromatographic separation.

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    How many times can I reuse my flash chromatography column?

    November 21, 2019 at 3:40 PM / by Bob Bickler posted in Chromatography Fundamentals, Sfär, Cost, Normal Phase

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    Flash chromatography – a purification tool for both organic chemists and natural product researchers.  This tool is essential when you need to remove impurities from your targeted product, or products, in order to get them pure.  To reduce the costs associated with flash chromatography, some chemists try reusing the same column over and over, not always with success.

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    Organic Chemistry Workflow – Typical Steps and Equipment

    November 12, 2019 at 3:04 PM / by Bob Bickler posted in Workflow, Sfär, Selekt, Loading Techniques, Normal Phase, V-10, Pillar Page, Initiator

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    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.

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    The Step Gradient Explained

    November 1, 2019 at 9:37 PM / by Greg Saunders posted in Chromatography Fundamentals, Solvents, Green, Cost, Normal Phase, Isolera

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    Up to six compounds can be easily separated with an automated step-gradient optimizer embedded in modern flash chromatography systems.

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    How to prevent compound precipitation during flash column chromatography

    November 1, 2019 at 9:34 PM / by Bob Bickler posted in Reversed-phase, Solvents, Troubleshooting and Optimization, Selekt, Loading Techniques, Normal Phase, Isolera

    4 Comments

    Compounds precipitating during flash chromatography is at best an inconvenience when working up your crude reaction mixture.  Precipitation during purification typically happens in the column or in the tubing exiting the column.

    In this post, I will propose a strategy that can minimize and perhaps prevent this issue from occurring.

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

    November 1, 2019 at 9:30 PM / by Bob Bickler posted in Chromatography Fundamentals, Media and Resin, Normal Phase

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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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    Why are my flash column chromatography peaks splitting?

    November 1, 2019 at 9:19 PM / by Bob Bickler posted in Troubleshooting and Optimization, Normal Phase

    2 Comments

    Split peaks? Multiple peaks? Are they really a problem? What causes the issue?

    In this post I will discuss what split peaks are and what to do to fix the problem.

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    Which sorbents work best for dry loading flash column chromatography samples?

    October 18, 2019 at 10:05 PM / by Bob Bickler posted in Chromatography Fundamentals, Solvents, Media and Resin, Normal Phase

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    For chemists needing to purify natural product extracts or synthesis reaction mixtures flash chromatography is typically the tool of choice. In previous posts I have discussed various ways to optimize the purification to obtain the highest purity compounds with maximum load in minimal time.

    Sometimes, though, chemistry gets in the way in the form of solubility issues. When this happens most often dry loading is recommended for these sample types. In this post I will show the impact various dry load sorbent options have on chromatography.

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