Why do I see more peaks than I expect with flash column chromatography?

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. Continue reading Why do I see more peaks than I expect with flash column chromatography?

Using pH to optimize reversed-phase flash chromatography separations

I have previously posted on the topic of normal-phase optimization by evaluating different solvent blends or mixtures. I have also touched on reversed-phase method development as well suggesting chemists use HPLC to optimize their purification.

In this post, I will look at the impact modifying mobile phase pH can have on reversed-phase separations.

Continue reading Using pH to optimize reversed-phase flash chromatography separations

How do I remove an annoying MS TIC background?

Have you ever run flash column chromatography with mass detection (Flash-MS) and observed the total ion current or TIC increase during the purification only to find that there was no discernible compound contributing to the effect?

In this post I discuss how I came across this issue and the solution I found to work.

Continue reading How do I remove an annoying MS TIC background?

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

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 transferrable from TLC.

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

Why is my UV baseline changing during flash column chromatography?

A baseline that rises or drops when using flash chromatography with a UV detector can be a problem, especially if you are trying to collect compounds with poor detectability or that exist in low quantities.

In this post I will talk about the causes and solutions for a rising (or even dropping) baseline. Continue reading Why is my UV baseline changing during flash column chromatography?

Does mass detection make-up solvent choice matter?

An interesting question, at least to me. Depending on the detector brand, some mass spectrometer manufacturers recommend acetonitrile while others recommend methanol. Is there a real difference between these solvents?

In this post I look at how acetonitrile and methanol compare when used with an APCI source.

Continue reading Does mass detection make-up solvent choice matter?

In-line scavenging simplifies flash column chromatography reaction mixture purification

I am always grateful for the feedback I get from my blog readers.  Today’s blog is in response for multiple requests for  tips on purifying complex mixtures and suggestions for alternative sample loading techniques.

In this post, I will attempt to address both, to some degree anyway, with a single example using a scavenger resin.

Continue reading In-line scavenging simplifies flash column chromatography reaction mixture purification

What is the optimal sample to sorbent ratio for dry loading in flash column chromatography?

For chemists preferring or needing to dry load their crude sample mixtures to get an acceptable flash purification result, using the right ratio of sample to sorbent can be quite important.  Too much sample and solubility issues can ensue, too little sample and significant band broadening occurs, reducing the separation quality.

In this post, I propose an acceptable ratio range based on my own experimental data.

Continue reading What is the optimal sample to sorbent ratio for dry loading in flash column chromatography?

Using adducts and fragments to identify compounds in mass-directed flash chromatography

Over the past several years, automated flash chromatography has evolved to include in-line mass detection.  Typically, these single-quadrupole mass detectors are outfitted with either an atmospheric pressure chemical ionization source (APCI) or an electrospray chemical ionization source (ESI).  While this technical advance in flash chromatography has helped chemists detect and isolate pure compounds with a known molecular weight, verifying the identity of that compound can sometimes be a challenge as the detected mass may not match that which you expect due to fragmentation and/or adduct formation.

In this post I will offer some assistance in determining adducts and fragments.

Continue reading Using adducts and fragments to identify compounds in mass-directed flash chromatography