title: Combining Chemometric Models with Adsorption Isotherm Measurements to Study Omeprazole in RP-LC.
abstract: The adsorption of the proton-pump inhibitor omeprazole was investigated using RP-LC with chemometric models combined with adsorption isotherm modelling to study the effect of pH and type of organic modifier (i.e., acetonitrile or methanol). The chemometric approach revealed that omeprazole was tailing with methanol and fronting with acetonitrile along with increased fronting at higher pH. The increased fronting with higher pH for acetonitrile was explored using a pH-dependent adsorption isotherm model that was determined using the inverse method and it agreed well with the experimental data. The model indicated that the peaks exhibit more fronting at high pH due to a larger fraction of charged omeprazole molecules. This model could accurately predict the shape of elution profiles at arbitrary pH levels in the studied interval. Using a two-layer adsorption isotherm model, the difference between acetonitrile and methanol was studied at the lowest pH at which almost all omeprazole molecules are neutral. Omeprazole had adsorbate-adsorbate interactions that were similar in strength for the acetonitrile and methanol mobile phases, while the solute-adsorbent interactions were almost twice as strong with methanol. The difference in the relative strengths of these two interactions likely explains the different peak asymmetries (i.e., tailing/fronting) in methanol and acetonitrile. In conclusion, thermodynamic modelling can complement chemometric modeling in HPLC method development and increase the understanding of the separation.
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, 651 88 Karlstad, Sweden.
authors.forename: Dennis
authors.initials: D
authors.lastname: Åsberg
authors.affiliation: Department of Chemical and Process Engineering, Rzeszów University of Technology, 35 959 Rzeszow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Leśko
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, 651 88 Karlstad, Sweden.
authors.forename: Jörgen
authors.identifier: 0000-0003-1819-1709
authors.initials: J
authors.lastname: Samuelsson
authors.affiliation: AstraZeneca R&D Gothenburg, 431 83 Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Department of Chemical and Process Engineering, Rzeszów University of Technology, 35 959 Rzeszow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kaczmarski
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, 651 88 Karlstad, Sweden.
authors.forename: Torgny
authors.identifier: 0000-0002-7123-2066
authors.initials: T
authors.lastname: Fornstedt
keywords: Adsorption isotherm; Design of experiments; Liquid chromatography; Omeprazole; pH