Use of potentiometric detection in (ultra) high performance liquid chromatography and modelling with adsorption/desorption binding kinetics

[Display omitted] •The first use of a potentiometric detector in UPLC is described.•The potentiometric detector is also used in HPLC.•Alkaloids were sensitively determined.•A model is given that describes how adsorption/desorption kinetics determines the detector characteristics.•Binding kinetics can be performed with the detector, in Flow injection analysis. Observation of a potentiometric sensor's response behaviour after injection in flow injection analysis at different concentrations allowed studying “on” and “off” kinetics of the analyte's adsorption/diffusion behaviour. The alkaloid metergoline was mostly used as an example. kon and koff rate constant values were measured, and the association constant Kass, and ΔG values of the analyte–surface interaction were calculated with an adsorption-based model which proved to be fully applicable. kon increased by decreasing the sensor dimensions, while koff was unaffected by miniaturization. Increasing acetonitrile concentrations in the running buffer increased koff, while kon was unaffected. The experimentally determined ΔG values of the analyte–surface interaction showed a linear relation to the response of the sensor, in mV. This knowledge was applied to optimize the potentiometric detection of plant alkaloids in (U)HPLC. Sub-micromolar detection limits were obtained with the potentiometric detector/(U)HPLC combination. This is the first time that the response rates and the response itself can be modelled accurately for coated wire potentiometric sensors, and it is the first application of a potentiometric detector in UPLC.