Flash purification is a preparative liquid chromatography technique. As such, it incorporates the same types of components as preparative high-pressure liquid chromatography (pHPLC) – pump, gradient mixer, column, UV detector, and fraction collector. Though all flash chromatography systems are purpose-built and essentially work the same, the one area of difference is in the UV detector design and operation.

Are you observing more chromatographic peaks than you expect compared to TLC or other assessment data?  Well, it could be that your method is separating some isomers or, it could be that there is an actual method issue.

In this post I will discuss what could cause a method issue and suggest some ideas as to how to fix it.

Evaporative Light-Scattering Detection, or ELSD for short, is a technology used with liquid chromatography to see UV-transparent (and UV-absorbing) compounds. In a previous post I talked about some applications where ELSD is not only useful, but required.

In this post, I will explain how an ELSD is configured and functions.

With reversed-phase flash column chromatography becoming increasingly popular for routine purification, understanding how to make the cartridges last (since they cost more) is important to know. 

In this post I will mention a few tips to prolong reversed-phase cartridge life.

I am often asked why reversed-phase TLC data does not translate well to reversed-phase flash column chromatography.  There are several reasons for this and in this post I will attempt to explain the challenges associated with reverse-phase TLC as a method development tool for reversed-phase flash chromatography.

In a previous post I talked about column size, specifically long-thin versus short-fat and the impact of the cartridge’s dimensions on purification performance. With that comparison I showed that in preparative chromatography, purification efficiency is more about the amount of silica than column dimensions. Cartridges of different dimensions containing the same amount of the same media will provide the same separation efficiency.

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.

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.

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.

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.

When it comes to the purification of polar, water-soluble compounds reversed-phase chromatography is the most commonly used approach. However, because of strong stationary phase – mobile phase repulsion forces, the use of highly aqueous (90-100% water) solvent systems has been shown to provide less retention than needed.  This issue has led to the development of “aqueous compatible” reversed-phase media.

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.

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.

For most organic reaction mixture purifications the process is fairly straightforward. Use hexane/ethyl acetate or, for polar compounds, DCM/MeOH.  But what do you do if this doesn't work and your compounds are basic organic amines?

In this post, I re-examine the options available to achieve an acceptable organic amine purification when typical separation methods are insufficient.

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.

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.