Csaba Horváth and preparative liquid chromatography.
Few chromatographers have been interested in furthering preparative liquid chromatography. The pioneers, Tswett, Kuhn and Lederer, A.J.P. Martin, Tiselius, isolated fractions but as an intermediate step in the analysis of their samples. The progress in electronics and sensors, and in their miniaturization has lead to the paradoxical situation that the analysts never see the transient pure fractions that their detector quantitates. Yet, over the last 25 years, preparative liquid chromatography has become an important industrial process for the separation, the extraction, and/or the purification of many pharmaceuticals or pharmaceutical intermediates, including pure enantiomers, purified peptides and proteins, compounds that are manufactured at the relatively large industrial scale of a few kilograms to several hundred tons per year. This development that has strongly affected the modem pharmaceutical industry is mainly due to the pioneering work of Csaba Horváth. His work in preparative HPLC was critical at both the practical and the theoretical levels. He was the first scientist in modem times to pay serious attention to the relationships between the curvature of the equilibrium isotherms, the competitive nature of nonlinear isotherms, and the chromatographic band profiles of complex mixtures. The thermodynamics of multi-component phase equilibria and mass transfer kinetics in chromatography attracted his interest and were the focus of ground-breaking contributions. He investigated displacement chromatography, an old method invented by Tiselius that Csaba was first to implement in HPLC. This choice was explained by the essential characteristic of displacement chromatography, in that it delivers fractions that can be far more concentrated than the feed. Remarkably, once the basics of nonlinear chromatography had been mastered in his group, most of the applications that were studied by his coworkers dealt with peptides of various sizes and with proteins. Thus, all the applications of preparative HPLC in the biotechnologies derive directly from Csaba's work. Although displacement did not pan out as a general method, the reasons are related more to practical constraints of the production of pharmaceuticals and to the long period of cheap energy that might be ending now. This report reviews Csaba's work in nonlinear chromatography.
Guiochon
Georges
G
Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600, USA. guiochon@utk.edu
D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000266:history / Q000379:methods*; D049673:History, 20th Century; D049674:History, 21st Century; D007700:Kinetics; D013816:Thermodynamics