QbD Based Method Development on an Agilent 1290 Infinity UHPLC System Combined with a Seamless Method Transfer to HPLC Using Intelligent System Emulation Technology

In this Application Note, a method was developed on sub-2 μm particle columns and transferred to a conventional HPLC method using Quality by Design (QbD) principles. A seamless method transfer between the different chromatography systems was achieved using the Agilent Intelligent System Emulation Technology (ISET). Initial method development work on the Agilent Infinity 1290 system included automated chemistry screening of different sub-2 μm particle columns under different chromatographic conditions involving multiple combinations of eluents, flow rates, gradient slopes, and temperatures. Subsequent optimization of the best performing chemistry system was carried out using a Design of Experiments (DOE) approach to establish the ICH Design Space. The Agilent Method Translator was used for the transfer from sub-2 μm column material to conventional column material. An Agilent 1290 Infinity UHPLC system was used in combination with ISET to emulate an Agilent 1260 Infinity HPLC system. This enabled establishing a Design Space for the HPLC method. Reproducibility and resolution of the transferred method was then verified on an Agilent 1260 Infinity HPLC system. This successfully demonstrates that ISET in combination with Fusion QbD Method Development and Validation Software (S-Matrix) enables an efficient transfer of UHPLC methods to HPLC methods within the QbD approach.