Sharper​ Peaks Ahead Chromatography Blog

How not to do flash chromatography

Written by Josh Lovell | Mar 12, 2025 1:04:18 PM

Save time, save money, stay safe: manual vs. automated flash chromatography

Automated chromatography systems such as those offered by Teledyne LABS’ ISCO brand have been the norm in the pharmaceutical lab for years. That’s not always the case in cash-strapped, resource-savvy organizations and institutions. Academia is a prime example.

There, you’ll often find conclaves of graduate students (myself formerly included) struggling over the manual process of flash chromatography — mixing silica gel in solvent, pouring it into a glass column and pushing the solvent through with a stream of air or nitrogen. You’ll also witness students struggling to hold the whole apparatus down with one hand while grasping the active column in the other, then juggling test tubes or flasks to collect the effluent.

It’s an historic yet cumbersome method for teaching chromatographic theory, but the results are generally less accurate and the process far slower (which in the working world, where time is money, means added expense and lower productivity) than using automated systems. Additionally, students don’t gain experience in operating the types of instruments, analyzing the enhanced separations, and using the purer results yielded by the automated systems they’ll be expected to run post-graduation.

The manual process also is prone to mishaps and errant outcomes that range from a poor separation to outright dangerous results. In addition to shattering your dreams of the perfect run, you could very well shatter your column. I recently reencountered a post from medicinal chemist Derek Lowe’s “In the Pipeline” blog entitled How Not To Do It: Column Chromatography, where he described a real-life occurrence highlighting the risks inherent to flash chromatography.

The anecdote involves a grad student running a manual process who packed dry silica gel into a column and ran solvent through it before loading the sample, which is time-consuming and wastes solvent. His mobile phase of choice? Dimethyl sulfoxide (DMSO).

DMSO is an extremely strong solvent and, to use a scientific term, gooey. That means getting it to work would be a laborious task taking an exceptional amount of time (there’s that waste of time theme again). DMSO gets very hot, very quickly, when it wets the dry silica. So, when the student forced a big, rounded mass of DMSO down his dry column, the result was the startling snap of the column cracking, a noise that could be heard two classrooms away. As if that weren’t unsettling enough, the column’s contents oozed all over the table and the student’s hands. (I will save sharing [ranting about] my personal experience in using glass columns under pressure for another post.)

Alternatively, investing in an automated system can be far safer and economical in the long run. Read more about the best practices for safely performing flash chromatography here. The instrument and processes are far less prone to mishap and the results are far more precise and valuable. You buy the columns of silica gel pre-packed and plug whatever size you need into the chromatography instrument. Then you load your sample on, tell the system what solvents you’re using, position a rack of test tubes, push a button and go be productive elsewhere while the system works for you.


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