Screening of the most relevant parameters for method development in ultra-high performance hydrophilic interaction chromatography

► A dataset of 82 drugs presenting very diverse physico-chemical properties was investigated. ► Five different polar stationary phases packed with sub-2 μm particles were tested. ► The Agilent Zorbax RRHD was the most versatile HILIC column packed with sub-2 μm particles. ► The nature of the stationary phase and mobile phase pH are the most important parameters for HILIC method development. ► Screening four different stationary phases and two pH appear to be the best initial step for successful HILIC method development.