A workflow for column interchangeability in liquid chromatography using modeling software and quality-by-design principles

摘要

Graphical abstract Display Omitted Highlights ? We developed UHPLC method strategy for investigation of column interchangeability using modeling software. ? The selected four stationary phases have some obvious differences in terms of surface area, coverage, carbon load and endcapping, but three of them could provide baseline separation in the same design space. ? At the end, by using LC modeling software, it was found that two of the four columns share the same working point and are robust around this condition. ? The predicted results were in good agreement with the experimental ones. Abstract The goal of the present study was to develop a generic workflow to evaluate the chromatographic resolution in a large design space and easily find some replacement column for the method. To attain this objective from a limited number of initial experiments, modern LC modeling software (Drylab) was employed to study the behaviour of the compounds and visually compare the parts of design spaces obtained with different columns, where a given criterion of critical resolution is fullfilled. A zone of robust space can then easily be found by overlapping design spaces. By using 50×2.1mm columns packed with sub–2μm fully porous particles (UHPLC), the resolution in the entire design space can be modeled on the basis of only 2–3h experimental work per column. To demonstrate the applicability of the developed procedure, amlodipine and its related pharmacopeia impurities were selected as a case study. It was demonstrated that two columns from different providers (Waters Acquity HSS C18, Thermo Hypersil Gold C18) can be interchanged, providing a sufficient resolution at the same working point and a high degree of robustness around this condition.