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With the ACN shortage showing few signs of letting up in the near future, ACN-free methods such as SFC are receiving increased attention and interest. Here our experts discuss this technique.
What impact has the acetonitrile shortage had on the use of SFC? Do you believe this impact will be lasting or is it temporary?
Berger: The acetonitrile shortage will have little impact on SFC. We have seldom used it in the past. It's greatest utility came from its transparency in the UV down to 195nm, which may be important for compounds with very weak chromophores. I also recall a few cases where solutes reacted with alcohols making acetonitrile an obvious alternative.
HPLC users will undoubtedly switch many new methods to methanol or ethanol, but they are stuck with all those methods approved by the FDA. Acetonitrile is inherently fairly toxic. I would guess there will be a general movement away from acetonitrile and it will mostly be used only in those regulated markets. Lower usage should bring the price down at least somewhat.
I suppose the regulated methods will accelerate the penetration of UHPLC or just smaller ID columns, in order to use lower volumes of acetonitrile.
Since chromatographers will need to change their traditional approach (reversed phase with acetonitrile/water) this may actually give them an additional incentive to try SFC. I should point out that 3 μm particles in SFC are about as fast as 1.8 μm particles in UHPLC, and require lower pressures, like those in traditional HPLC's!
Palcic: I believe that there will be a continued shift away from acetonitrile towards the new high pressure/low volume HPLC and CO2-based SFC technology. SFE will play more of a role when government regulations or solvent expenses increase to a point that instrumentation companies like us see the market for a more compact and automated platform. If hexane/heptanes prices return to last year's levels for an extended period of time, then labs will look for environmentally friendly and inexpensive ways to operate technologies like SFE.
Tognarelli: The "green" aspect of SFC has always appealed to chromatographers, but the recent acetonitrile shortage and the associated dramatic price increase further expanded the interest of previously unexplored markets. Although acetonitrile supplies may be at normal levels by as early as the second half of this year, current economic trends regarding production of materials, of which acetonitrile is a by-product, suggests prices may remain at currently inflated levels.
What is the future of Sample Prep SFC?
Berger: I believe in the long run SFC will simply be considered the way to do normal phase HPLC, using the same hardware for both normal and reversed phase. As I have often said, SFC is normal phase chromatography on steroids, with none of the traditional problems, and applicable to much more polar solutes.
SFC should become a major technique for any small molecule samples. Penetration into new QA/QC and regulated applications will be critical for this to happen. The instrumentation must be robust and easy to validate. I think we are getting there.
Palcic: This answer could take up 10 pages of your magazine. In short, SFC will dominate the separation of chiral molecules for preparative applications in the short term and analytical applications in the long term. Beyond that, SFC is likely to take a large percentage of the overall small molecule preparative market space and eventually play a larger role in analysis of metabolites, flavors and fragrances, petrochemicals, biofuels, pesticides, insecticides, and fertilizers.
Tognarelli: As SFC becomes more commonplace in laboratories, we foresee a more open access style of sample analysis of both chiral and achiral purifications, thereby expanding the use beyond analytical chemistry.
What is one change/improvement you hope to see in the SFC industry over the next few years?
Berger: I hope to see SFC become a mature technology without the proprietary software, and the "garage shop" kludges forced on small instrument companies by limited financing and low volumes.
Palcic: The market will see more SFC instruments integrated with high definition mass spectrometry, SFE and SFC instruments capable of flash chromatography–like performance and an all-in-one general purification platform combining SFC and HPLC systems to provide a total solution.
Tognarelli: As more manufacturers begin exploring the SFC market and awareness of SFC increases, it is our hope that the use of SFC expands to support a greater variety of standard chromatography applications.
Aurora SFC Systems, Inc.
TharSFC, a Waters Company