Achiral SFC – In at the deep end!

Using SFC for chiral separations is a no brainer, but until recently we hadn't really thought about the practicalities of using SFC for achiral purification.

The benefits of SFC chiral chromatography: fewer salt issues, reduced solvent, faster dry down, higher throughput, faster column equilibration, can all be applied to achiral samples too. The only negative when compared to reverse phase is the lack of a C18 equivalent 'one column certainly doesn't fit all'.

The bench mark in achiral reverse phase is C18. We turn to this phase immediately when starting method development work. Unfortunately there is not an equivalent when it comes to SFC and after extensive reading and searches, looking at 2-EPs, Silicas, Hilics and Nitros we found ourselves back at the beginning when trying to choose a column. So we chose them all!

With a newly stocked suite of 10 Achiral SFC columns and a few standards under our belt, we were up and running, waiting for our first 'simple' real sample to purify by SFC as an alternative to reverse phase. Then it arrived...

Real? Yes! Simple? No!

Our first achiral sample for purification by SFC, a multi component mixture! And this separated on bare silica...


The chromatogram above shows the multicomponent separation run on a 5-50% gradient over 16 minutes. With most SFC's designed for chiral separations, an open bed fraction collector was not available to us. We had 4 collection vessels. Therefore splitting the initial mixture into 4 and isolating the main peak and latest eluting peak gave us two clean peaks and two further mixtures which we were then able to method develop further.

4 Days later and...

Our first real go at achiral SFC was tricky but successful. We were certainly more than grateful of the lack of water to evaporate considering this sample required several passes. Since then we have processed a range of samples from Ultrapure to impurity isolations with the same level of success.

So this is the headline from our initial entry to achiral SFC; the drawback of the extended screening and method development time are more than balanced by the reduced post processing time and faster methods. SFC seems to be a winner for achiral samples too.

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Final sample manipulation is sped up by our Biotage V10, allowing us to return samples within the same week!…