Kinetic plot method as a tool to design coupled column systems producing 100,000 theoretical plates in the shortest possible time

The present paper reports on the possibility to use the kinetic plot method (KPM) to select and design the best possible system to achieve a given number (100,000) of theoretical plates for a pharmaceutical test mixture, using the information obtained from a series of single column performance measurements of sub-2 μm and supra-2 μm porous shell particles conducted at three different temperatures and using mixtures of acetonitrile and 0.1% formic acid in water as the mobile phase. Because the KPM involves an extrapolation to different column lengths, the quality of the design was subsequently verified by coupling several columns to achieve the optimal total column length and run the actual analysis at the calculated optimal flow rate. The prediction error was generally better than 10%, with a slightly better prediction for t0 and N than for the retention time tR. The sub-2 μm and the porous shell particle coupled column systems achieve the 100,000 plates about equally fast, despite the fact that the former were used at 1000 bar and the latter only at 600 bar. The high temperature operation (80 °C) yielded the fastest separation in both cases, allowing to reach 100,000 plates for a component eluting at k′ = 2.5 in only about 15 min.