Pharmaceutical applications on columns packed with sub-2 microm particles.

During the last few years, there has been a great interest in the development of fast liquid chromatography. Among the reported approaches, the reduction of the particle size to attain sub-2microm diameter represents a good solution for achieving both increased separation power and faster analysis time. This paper demonstrates the chromatographic performance of such supports using plate-height curves and reveals the possibility for obtaining ultra-fast or highly efficient separations, according to the column geometry and system pressure limitations. The stability of these columns is initially evaluated using a system suitability experiment. The chromatographic performance remains stable in terms of retention, efficiency, and pressure for more than 1700 injections with pressure conditions ranging from 200 to 800 bar. Several fast and ultra-fast pharmaceutical applications are reported. In isocratic mode, a 5- to 10-fold reduction in analysis time is obtained with limited influence on efficiency and resolution. The run time is further reduced by 30-fold with the shorter available columns (i.e., 30 mm length). In gradient mode, the separation of a complex mixture containing an active pharmaceutical compound and related impurities is significantly improved with column length equal to 100 mm, to increase peak capacity and resolution.