Directly from its beginning—now 100 years ago, when Michail Tswett developed the principles [1, 2] with the isolation of chlorophyll—chromatography has always been a preparative technology, and its value in producing compounds of high purity cannot be overemphasized. It was Paul Karrer [3] who stated very early “. . . it would be a mistake to believe that a preparation purified by crystallization should be purer than one obtained from chromatographic analysis. In all recent investigations chromatographic purification widely surpassed that of crystallization.” and Leslie Ettre, although not distinguishing between analytical and preparative separations, denoted chromatography as “the separation. | 21 TRENDS IN PREPARATIVE HPLC Ernst Kuesters INTRODUCTION Directly from its beginning now 100 years ago when Michail Tswett developed the principles 1 2 with the isolation of chlorophyll chromatography has always been a preparative technology and its value in producing compounds of high purity cannot be overemphasized. It was Paul Karrer 3 who stated very early . it would be a mistake to believe that a preparation purified by crystallization should be purer than one obtained from chromatographic analysis. In all recent investigations chromatographic purification widely surpassed that of crystallization. and Leslie Ettre although not distinguishing between analytical and preparative separations denoted chromatography as the separation technique of the 20th century 4 . From a historical point of view the beginnings of preparative isolation of natural compounds were cumbersome. For example it is reported 5 that six years of work and processing of 30 tons of strawberries was needed to finally obtain 35 mL of an oil the essence of the fruit. This situation changed dramatically in the 1960s with the theoretical understanding of the chromatographic process the development of high-performance liquid chromatography and the synthesis of highly selective stationary phases. As a result of these improvements the isolation of natural compounds with preparative chromatography on production scale . drug substances from fermentation processes is still state of the art even after 100 years. Today preparative HPLC has also become a powerful technology in pharmaceutical development and production either for isolation of impurities for HPLC for Pharmaceutical Scientists Edited by Yuri Kazakevich and Rosario LoBrutto Copyright 2007 by John Wiley Sons Inc. 937 938 TRENDS IN PREPARATIVE HPLC TABLE 21-1. Order of Magnitude and Purpose of Purified Amounts Obtained from Preparative Chromatography Column Type . mm Purpose Amount of Stationary Phase g Amount of Product g Analytical
