Simulation of elution profiles in liquid chromatography – IV: Experimental characterization and modeling of solute injection profiles from a modulation valve used in two-dimensional liquid chromatography

Abstract Simulation software for liquid chromatography can accelerate method development capabilities. In two-dimensional chromatography this is particularly attractive because there are more method variables to consider, provided simulations can account for the effects of injection effluent from the first dimension separation into the second dimension column. In this paper we describe the adaptation of a previously described model (the Forssen model) to enable prediction of the profile of an injection pulse as it exits an Active Solvent Modulation (ASM) valve and enters the second dimension column under a variety of flow rate and sample loop size conditions (a global model). Experimentally measured injection profiles were used to train empirical models capable of generating injection profiles as a function of sample loop volume and flow rate. The resulting parameters were then used to generate an injection profile for a loop volume not used in the training set. The resulting profile agreed well with the experimentally obtained profile for this sample loop. Finally, chromatograms were simulated using previously developed simulation software incorporating the injection profile models developed in this work. Chromatographic peaks were simulated for valerophenone on an Agilent Zorbax C18 stationary phase with an acetonitrile/water mobile phase gradient. Results of simulations based on experimental injection profiles, profiles predicted using the Forssen or global models, and rectangular injection profiles were compared. Comparison of the resulting chromatographic peaks revealed good agreement between those produced using experimental profiles or the Forssen or global models, with less than ± 0.3% deviations for retention times and less than ± 10% deviations for the peak widths (expressed as σ).