Separations Anxieties

Chromatography is a continuously evolving science, and not a month goes by that some column or media manufacturer doesn’t tout the “next big thing.” In his 30 years in the business, Tom Jupille, founding consultant of , has seen enough to distinguish between the wheat and chaff. Jupille, who also presides over the eminently popular Chromatography Forum ( ), agreed to answer some of the pressing chromatography questions of the day. What have been the true innovations in HPLC equipment over the past year or so? On the analytical side, the continuing trend is “faster and smaller.” The efficiency of HPLC (measured by the infamous “theoretical plates”) has been roughly constant for a generation. The difference is that we are now generating 10,000 plates in 3-minute separations, compared to 30 minutes a couple of decades ago. This trend is continuing with the jump in operating pressure capability from about 5,000 psi to 10-15,000 psi over the past couple of years. Are you seeing more interest in chromatography for small molecules? What technologies (simulated moving bed, etc.) are driving this interest? What is limiting it? Process-scale chromatography of small molecules has always been a last resort, in large part because of the costs of the solvents required (chromatography will typically consume 5 to 10 times more solvent than something like a recrystalization or an extraction). There is some evidence that process-scale supercritical fluid chromatography (SFC) is changing the rules of the game by allowing the use of cheap, “green” mobile phases based on CO2. SFC is proving itself today in chiral purification; it remains to be seen whether increasing familiarization with the technology will extend that to other applications. Are new silicas significantly better than old ones? Which stand up best? Yes. The big (conceptual) improvement occurred a decade and a half