Technology Forum: HPLC-Chiral

The critical importance of Chiral HPLC to pharmaceutical research has made it a mainstay in the separations field. And with its wide range of applicability and high loading capacity, it will continue to be an integral technique, especially as costs decline and efficiency increases.

Joining us for this discussion are Nelu Grinberg of Boehringer Ingelheim Pharmaceuticals, Inc.; Todd Palcic of TharSFC, a Waters Company; and Jelena Kocergin of Regis Technologies, Inc.

Last year, several stationary phases were introduced to the HPLC-Chiral market as a cost-saving idea. How have these phases improved or shaped the HPLC-Chiral industry?

Grinberg:To my knowledge, the phases introduced last year are a result of the patent expiration from Diacel. These new phases are similar in price and performance to the ones from Diacel.

Palcic: Yes, our customers have told us that these terrific new phases have given chiral HPLC/SFC users morecost-effective options and equal or better performance from previous chiral columns.

Kocergin: It has definitely created some competition and introduced new companies as players in the chiral market. In my opinion this is a good thing, because having a choice usually creates new ideas and improves current products and services. We have seen some good chiral columns offered at economical pricing, although the price of chiral columns still remains quite high compared to conventional chromatography.

The acetonitrile shortage has had a major impact on the HPLC field as of late. How has it affected the field of HPLC-Chiral research?

Grinberg:I believe that the shortage of acetonitrile has had a minimal impact on the field of chiral research because:a. The majority of method developed is performed in normal phase, which employs organic solvents other than acetonitrile.b. The reversed phase methods can easily replace acetonitrile with methanol.

Palcic:I cannot say that the shortage has impacted the chiral SFC users who we know very well. Most chiral separations take place with normal phase solvents including CO₂, hexane, and heptane rather than reversed-phase solvents like water and acetonitrile.

Kocergin:While certainly affecting chiral research, the shortage of acetonitrile probably had less of an impact on chiral chromatography compared to its impact in conventional HPLC. This is due to the fact that normal phase chromatography is a big part of chiral HPLC and chiral stationary phases are well suited for normal phase HPLC. In addition, the use of supercritical fluid chromatography, which does not use acetonitrile, is quite popular in chiral research. It is a more common alternative for chiral research than conventional HPLC. This may change in future.

What trends do you see emerging in HPLC-Chiral?

Grinberg:The development of sub 2 mm particle size chiral stationary phases for separation of enantiomers.

Palcic:It appears clear to me that nearly all chiral separations laboratories in drug discovery environments have purchased or plan to purchase SFC technology - particularly for preparative applications. The drug development/methods development crowd previously remained focused on normal phase HPLC but they too accelerated their plans to shift to HPLC after several new products were introduced. We are beginning to ship those systems here in the second half of the year. Therefore, we will have to wait and see how SFC impacts the chiral QA/QCcommunity.

Kocergin:At the moment, small particle size seems to be of some interest in chiral HPLC. Also, covalently bonded phases are becoming more popular, offering greater choices for solvent compatibility. Still, traditional materials are predominantly used in chiral HPLC.

What is the future of HPLC-Chiral? Do you see it expanding into larger markets or remaining the same with necessary improvements over the years?

Grinberg:HPLC-Chiral, while very important, is a smaller market compared with the regular non-chiral market. As a consequence, the market will remain the same with minor improvements.

Palcic:As I have stated in the past, as SFC volumes increase, the products will become more standard and offer a lower cost of entry. This rapid uptake is coming soon as will new products.

Kocergin:Chiral HPLC has been a growing technique in recent years. I think it will continue to expand.

What is one change/improvement you hope to see in the HPLC-Chiral industry over the next few years?

Grinberg:I hope to see trial and error in method development eliminated. This can be done through a good understanding of the chiral separation process.

Palcic:Customers have asked us for a multichannel or parallel chiral methodsdevelopment system for a few years and finally we have completed thisdevelopment and will ship the first three of these systems to the firstcustomers at large pharmaceutical research sites in the U.S. and Europe inJuly. Although chiral SFC is much faster than HPLC, customers seek toimprove to even greater speeds and they can now do this in a smallerfootprint than they could with a one channel system a few months ago.This is truly an exciting time for chiral solutions.

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