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 × 2.1 mm columns packed with sub–2 μm fully porous particles (UHPLC), the resolution in the entire design space can be modeled on the basis of only 2–3 h 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.