Welcome to the Biotage Flash Purification Blogs.

    Bob Bickler


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    What is a step gradient and why should I use it?

    September 27, 2022 at 2:07 PM / by Bob Bickler posted in gradient, step gradient

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    Most chemists I meet utilizing flash chromatography use linear gradients. These gradients are either very generic (X% to Y% over a certain time or volume) or can be complex with multiple slope changes and even isocratic holds. These complex gradients are often created during a purification to get the desired separation because the generic gradient does not provide enough separation for the target compound needing purification.

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    How does acid concentration impact reversed-phase flash chromatography?

    August 24, 2022 at 2:55 AM / by Bob Bickler posted in acid

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    Reversed-phase flash chromatography is extremely useful when purifying all types of compounds. Compounds that are charged or ionizable, however, typically need either a pH modifier (acid or base) or a buffer to better control compound retention, peak shape, and selectivity.

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    How important is flow rate in flash chromatography?

    August 9, 2022 at 1:54 PM / by Bob Bickler posted in flow rate, separation, linear velocity

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    I often get questions from customers about the influence of flow rate on their flash chromatography. Typically, the questions are…

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    Which solvents are best for terpene flash chromatography?

    July 6, 2022 at 2:59 PM / by Bob Bickler posted in UV, selectivity

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    Well, it’s spring as I write this, my favorite time of year, and the foliage is in various stages of bloom. I like the rebirth of nature and the floral aromas that emanate from the blooms. These botanical aromas are the result of the various terpenes and terpenoids in the plant which can be very different between species.

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    How to maximize UV detection sensitivity in flash chromatography

    June 21, 2022 at 4:11 PM / by Bob Bickler posted in Solvents, UV, wavelength, sensitvity

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    Automated flash chromatography has become an integral component of the workflows of both synthetic organic chemistry and natural product research. The most utilized chromatographic technique is normal-phase, which uses a polar stationary phase filled column (i.e. silica) and a mix of non-polar and moderately polar solvents, i.e. hexane or heptane and ethyl acetate (EtOAc), resp.

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    How to isolate impurities from a reaction product

    June 7, 2022 at 5:57 PM / by Bob Bickler posted in reaction, orthogonal, by-product, impuriity

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    Ensuring that the product of a reaction is pure is critical to that compound’s viability as a marketable entity. Impurities often require characterization if they are in excess of regulated limits. The isolation of these compounds can be quite challenging. 

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    How to avoid sample blowback when liquid loading

    May 24, 2022 at 2:19 PM / by Bob Bickler posted in flash chromatography, sample, liquid, pressure

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    Ever experience the problem where you load your dissolved sample into a flash column via a syringe only to encounter either resistance or “blowback”? Blowback is a term describing the situation where your sample does not stay in the column but flows back out of the column’s cap after the loading syringe is removed.

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    When do I need to use an ELSD with flash chromatography?

    May 11, 2022 at 2:16 PM / by Bob Bickler posted in Detector, UV, elsd

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    Flash chromatography can be complex. Solvent choice, column size, stationary phase, loading technique, gradient method, flow rate, and detection parameters are all variables which factor into flash chromatography and your success with this purification technique. Of these variables, detection parameters, i.e. the type of detector, can really impact your flash chromatography results.

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    Is reversed-phase flash chromatography less expensive than normal-phase?

    April 26, 2022 at 2:41 PM / by Bob Bickler posted in Reversed-phase, Cost, Normal Phase

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    For many labs on a tight budget, keeping expenses at a minimum is crucial. Many of these same labs are also required to become more sustainable, or greener, by reducing the amount of organic solvent they use. Reducing solvent also reduces expenses, but what is the impact on lab productivity?

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    What is the maximum flash column sample load volume?

    April 12, 2022 at 9:40 PM / by Bob Bickler posted in loading capacity, solvent

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    A fairly common question I receive is "how much of my reaction mixture can I load on my flash chromatography column?". To this question there is not a cut and dry answer because of a number of variables which influence the outcome. To help illustrate this, I will show in this post the results of a study I performed in my lab with one of my reaction mixtures.

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    When is Gradient Elution Better than Isocratic Elution?

    March 30, 2022 at 2:00 PM / by Bob Bickler posted in isocratic, linear gradient, step gradient

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    Gradient or isocratic elution, that is the question. Within flash chromatography these are the options afforded to separate reaction mixtures and natural product extracts and is the focus of this post.

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    How should normal-phase gradient solvents be chosen?

    March 14, 2022 at 1:43 PM / by Bob Bickler posted in Solvents, Normal Phase, gradient

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    Normal-phase flash chromatography is an integral component of the organic synthesis workflow. Since reactions rarely generate 100% pure product, they need purification and flash chromatography is the most utilized tool for that task.

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    How many times can I reuse my reversed-phase flash column?

    February 22, 2022 at 2:41 PM / by Bob Bickler posted in Reversed-phase, Reuse, flash chromatography

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    Reversed-phase flash chromatography use continues to increase for a variety of reasons. Unlike silica normal-phase flash columns, which typically are used only once, reversed-phase flash columns can be cleaned, stored, and reused. How many times can a column be reused is a frequent question I receive. In this post, I will do my best to answer this question.

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    How does reagent concentration impact synthesis?

    February 8, 2022 at 6:00 PM / by Bob Bickler posted in Solvents, Synthesis, microwave, concentration

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    As you know, reaction chemistry involves determining and selecting the right conditions for optimal product yield and purity. There are actually six variables, that I know of, needing consideration including…

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    When Should I Replace My Flash C18 Column?

    January 25, 2022 at 3:36 PM / by Bob Bickler posted in Reversed-phase, replace

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    Knowing when it is time to replace your reversed-phase flash column is a question I am asked frequently along with…

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    How Scalable is Flash Chromatography?

    January 11, 2022 at 2:08 PM / by Bob Bickler posted in Scale-Up, reaction, scale

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    Flash chromatography is the most commonly used purification tool for organic and medicinal chemists whose reaction scales typically range from milligrams to grams. The column size to be used for the purification of these reaction mixtures is selected either by using the 1% rule which states that for many reaction mixtures, a crude reaction mixture load equaling 1% of the column’s media weight often will provide the needed purity, assuming the right elution method is selected. While this strategy can work, often chemists either overload or underload the selected column resulting in low product purity which requires re-purification. In both situations, the chemists wastes time, solvent, and the cost of the column.

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