Inter-instrumental method transfer of chiral capillary electrophoretic methods using robustness test information

Abstract

Capillary electrophoresis (CE) is an electrodriven separation technique that is often used for the separation of chiral molecules. Advantages of CE are its flexibility, low cost and efficiency. On the other hand, the precision and transfer of CE methods are well-known problems of the technique. Reasons for the more complicated method transfer are the more diverse instrumental differences, such as total capillary lengths and capillary cooling systems; and the higher response variability of CE methods compared to other techniques, such as liquid chromatography (HPLC). Therefore, a larger systematic change in peak resolutions, migration times and peak areas, with a loss of separation and efficiency may be seen when a CE method is transferred to another laboratory or another type of instrument. A swift and successful method transfer is required because development and routine use of analytical methods are usually not performed in the same laboratory and/or on the same type of equipment. The aim of our study was to develop transfer rules to facilitate CE method transfers between different laboratories and instruments. In our case study, three β-blockers were chirally separated and inter-instrumental transfers were performed. The first step of our study was to optimise the precision of the chiral CE method. Next, a robustness test was performed to identify the instrumental and experimental parameters that were most influencing the considered responses. The precision- and the robustness study results were used to adapt instrumental and/or method settings to improve the transfer between different instruments. Finally, the comparison of adapted and non-adapted transfers allowed deriving some rules to facilitate CE method transfers.