Chiral Screening

The bottle neck in a busy purification laboratory quite often is not the purification itself, but finding the right method. Chiral screening used to mean lots of waiting and probably lots of coffee, as each column was equilibrated and each method ran. It could easily take more than 40 minutes to test each condition. Whilst Supercritical Fluid Chromatography has helped to speed up the process (we’re down to less than 8 minutes a method) screening itself is still considered a bit of a black art.

With 88 SFC methods available, (we’ll talk about HPLC another time) there is still the potential for a full chiral SFC screen to take almost twelve hours. Whilst this is not bad for the number of methods, it isn’t ideal when fourteen chiral samples arrive on your desk at once! It’s days like those that led to the design of our tiered approach.

We now have four tiers. Across the four, each compound will see eleven different chiral stationary phases (CSPs) and eight mobile phase combinations, equalling 88 methods and a >95% hit rate. The key is to find as many of these hits within the shortest amount of time. Over a period of time all samples entering into the lab have, at one point or another, seen all 88 methods. This has allowed us to build up our own database. From this we have been able to select our most popular phases and solvents, naturally the most popular phases sit in our first tier. Tier one takes just 63 minutes to run and achieves a separation for 64% of samples that come into the lab. For those samples where tier one doesn’t work, tier two is employed, achieving another 23% in a further 72 minutes. The tiers continue as required for those samples that don’t fall within the 87%. For the majority of samples, a suitable prep method has been identified within the first 3 hours, moving it out of the analytical laboratory and marking it as ready for purification. Finding a suitable method during the working day allows us to begin the purification that afternoon and run into the evening, for small samples this is a huge benefit; we can now return these samples within three working days.

The more samples we screen the more tailored we can make the screening protocol. Incorporating the knowledge we acquire about our individual clients and their projects will allow us to personalise the screen and find methods even quicker. Which in turn, allows us to prep and return the isomers sooner, keeping everybody happy.