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  • 1.
    Asberg, Dennis
    et al.
    Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Weinmann, Annika Langborg
    AstraZeneca, Resp Inflammat & Autoimmun, Innovat Med & Early Dev Biotech Unit, SE-43183 Molndal, Sweden..
    Leek, Tomas
    AstraZeneca, Resp Inflammat & Autoimmun, Innovat Med & Early Dev Biotech Unit, SE-43183 Molndal, Sweden..
    Lewis, Richard J.
    AstraZeneca, Resp Inflammat & Autoimmun, Innovat Med & Early Dev Biotech Unit, SE-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca, Resp Inflammat & Autoimmun, Innovat Med & Early Dev Biotech Unit, SE-43183 Molndal, Sweden..
    Lesko, Marek
    Rzeszow Univ Technol, Dept Chem & Proc Engn, PL-35959 Rzeszow, Poland..
    Kaczmarski, Krzysztof
    Rzeszow Univ Technol, Dept Chem & Proc Engn, PL-35959 Rzeszow, Poland..
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    The importance of ion-pairing in peptide purification by reversed-phase liquid chromatography2017Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1496, s. 80-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adsorption mechanism for three peptides was studied under overloaded conditions through adsorption isotherm measurements in the presence of an ion-pairing reagent, trifluoroacetic acid (TFA), on an end-capped C18-bonded stationary phase. The overall aim of the study was to obtain a better understanding of how the acetonitrile and the TFA fractions in the eluent affected the overloaded elution profiles and the selectivity between peptides using mechanistic modelling and multivariate design of experiments. When studying the effect of TFA, direct evidence for ion pair formation between a peptide and TFA in acetonitrile-water solutions was provided by fluorine-proton nuclear Overhauser NMR enhancement experiments and the adsorption of TFA on the stationary phase was measured by frontal analysis. The adsorption isotherms for each peptide were then determined by the inverse method at eight TFA concentrations ranging from 2.6 mM to 37.3 mM (0.02–0.29 vol-%) in isocratic elution. The equilibrium between the peptide ion and the peptide-TFA complex was modelled by coupling the mass-balance to reaction kinetics and determining separate adsorption isotherms for the two species. We found that a Langmuir isotherm described the elution profile of peptide-TFA complex well while the peptide ion was described by a bi-Langmuir adsorption isotherm since it exhibited strong secondary interactions. The elution profiles had an unfavorable shape at low TFA concentrations consisting of a spike in their front and a long tailing rear due to the secondary interactions for the peptide ion having very low saturation capacity. The acetonitrile dependence on the adsorption isotherms was studied by determination of adsorption isotherms directly from elution profiles obtained in gradient elution which enabled a broad acetonitrile interval to be studied. Here, it was found that the column saturation capacity was quickly reached at very low acetonitrile fractions and that there were significant variations in adsorption with the molecular weight. Finally, practical implications for method development are discussed based on an experimental design where gradient slope and TFA concentrations are used as factors. (c) 2017 Published by Elsevier B.V.

  • 2.
    Cilpa-Karhu, Geraldine
    et al.
    Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki.
    Lipponen, Katriina
    Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Ööri, Katariina
    Wihuri Research Institute, FIN-00290 Helsinki, Finland.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Riekkola, Marja-Liisa
    Chemistry, Department of Chemistry, University of Helsinki.
    Three complementary techniques for the clarification of temperature effect on low-density lipoprotein–chondroitin-6-sulfate interaction2013Ingår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 443, nr 2, s. 139-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract A rigorous processing of adsorption data from quartz crystal microbalance technology was successfully combined with the data obtained by partial filling affinity capillary electrophoresis and molecular dynamics for the clarification of the temperature effect on the interaction of a major glycosaminoglycan chain chondroitin-6-sulfate (C6S) of proteoglycans with low-density lipoprotein (LDL) and with a peptide fragment of apolipoprotein B-100 (residues 3359–3377 of LDL, PPBS). Two experimental techniques and computational atomistic methods demonstrated a nonlinear pattern of the affinity of C6S at temperatures above 38.0 °C to both LDL and PPBS. The temperature affects the interaction of C6S with LDL and PPBS by influencing the structural behavior of glycosaminoglycan C6S and/or that of LDL.

  • 3.
    Elhamili, Anisa
    et al.
    Uppsala University, Sweden.
    Samuelsson, Jörgen
    Uppsala universitet.
    Bergquist, Jonas
    Uppsala University, Sweden.
    Wetterhall, Magnus
    Uppsala University, Sweden.
    Optimizing the extraction, separation and quantification of tricyclic antidepressant drugs in human plasma with CE-ESI-TOF-MS using cationic-coated capillaries2011Ingår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, nr 6-7, s. 647-658Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, the extraction and CE-ESI-TOF-MS analysis of tricyclic antidepressant (TCA) drugs imipramine, desipramine, clomipramine and norclomipramine in human plasma has been optimized. The CE capillaries were modified with omega-iodo-alkyl ammonium salt (M7C4I coating) to reduce analyte adsorption to the silica wall. The use of a strong cation exchange (SCX) solid-phase extraction (SPE) column specifically designed for the extraction of basic drug species from biofluids gave very clean extracts with high and reproducible recoveries. The extraction recoveries were ranging between 87 and 91% with % RSD values of 0.5-1.7% (n = 3). The obtained strong cation exchange-SPE extracts of the TCA in human plasma only contained the analytes of interest. The optimized CE separation conditions were obtained by adding ACN and acetic acid to the sample while using an aqueous BGE. The CE-ESI-TOF-MS analysis was performed within 6 min for all TCA analytes under the optimized condition with peak efficiencies up to 1.4 x 10(5) plates/m and an average % RSD of the migration times of the analytes of 0.3% (n = 5). The presented method can readily be used for the extraction and quantification of basic drug species in human biological fluids and in pharmaceutical formulations.

  • 4.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Asberg, Dennis
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Leek, Hanna
    AstraZeneca R&D, Resp Inflammat & Autoimmun, Innovat Med, S-43183 Molndal, Sweden..
    Ohlen, Kristina
    AstraZeneca R&D, Resp Inflammat & Autoimmun, Innovat Med, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Resp Inflammat & Autoimmun, Innovat Med, S-43183 Molndal, Sweden..
    Samuelsson, Jorgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Evaluation of scale-up from analytical to preparative supercritical fluid chromatography2015Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1425, s. 280-286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An approach for reliable transfer from analytical to preparative scale supercritical fluid chromatography was evaluated. Here, we accounted for the conditions inside the columns as well as to the fact that most analytical instruments are volume-controlled while most preparative scale units are mass-controlled. The latter is a particular problem when performing pilot scale experiments and optimizations prior to scaling up to production scale. This was solved by measuring the mass flow, the pressure and the temperature on the analytical unit using external sensors. Thereafter, it was revealed with a design of experiments approach that the methanol fraction and the pressure are the two most important parameters to control for preserved retention throughout the scale-up; for preserved selectivity the temperature was most important in this particular system. Using this approach, the resulting chromatograms from the preparative unit agreed well with those from the analytical unit while keeping the same column length and particles size. A brief investigation on how the solute elution volume varies with the volumetric flow rate revealed a complex dependency on pressure, density and apparent methanol content. Since the methanol content is a parameter of great importance to control during the scale up, we must be careful when changing operational and column design conditions which generates deviations in pressure, density and methanol content between different columns. (C) 2015 Elsevier B.V. All rights reserved.

  • 5.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Arnell, Robert
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Kaczmarski, Krzysztof
    A systematic investigation of algorithm impact in preparative chromatography with experimental verifications2011Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, nr 5, s. 662-672Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Computer-assisted optimization of chromatographic separations requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation. Furthermore, the competitive adsorption isotherms needed for optimization are often estimated numerically using the inverse method that also solves the ED equations. This means that the accuracy of the estimated adsorption isotherm parameters explicitly depends on the numerical accuracy of the algorithm that is used to solve the ED equations. The fast and commonly used algorithm for this purpose, the Rouchon Finite Difference (RFD) algorithm, has often been reported not to be able to accurately solve the ED equations for all practical preparative experimental conditions, but its limitations has never been completely and systematically investigated. In this study, we thoroughly investigate three different algorithms used to solve the ED equations: the RFD algorithm, the Orthogonal Collocation on Finite Elements (OCFE) method and a Central Difference Method (CDM) algorithm, both for increased theoretical understanding and for real cases of industrial interest. We identified discrepancies between the conventional RFD algorithm and the more accurate OCFE and CDM algorithms for several conditions, such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm, but better prediction using OCFE/CDM for a binary low efficiency separation problem or separations when the compounds have different efficiency. Our conclusion is to use the RFD algorithm with caution when such conditions are present and that the rule of thumb that the number of theoretical plates should be greater than 1000 for application of the RFD algorithm is underestimated in many cases

  • 6.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Arnell, Robert
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Kaczmarski, Krzysztof
    Computer Assisted Optimization of Pharmaceutical Purification - The Impact of Algorithms and Experimental Approach2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    Computer assisted process optimization of chromatographic separations requires the selection of computer algorithms and measurement of relevant parameters. In this study, we will investigate how the choice of algorithms and the number of performed initial experiments affect the estimated optimal separations conditions. We will focus on conditions typically encountered for slurry packing coated 20 µm CSP in large-scale columns used for pharmaceutical intermediate purification.Probably the most essential for parameters in this context are the adsorption isotherm parameters for the components. The rapid "inverse method" is commonly used and this method requires that one numerically solve the mass balance equations describing the chromatographic process. Here we thoroughly investigate how different algorithms that solve the Equilibrium-Dispersive (ED) mass balance equations will affect the estimated adsorption isotherm parameters.Furthermore, we will investigate and compare how different strategies affect the prediction of the optimal separation conditions. First, we will use a more rapid approach that requires a minimum of experiments and uses standard algorithms to estimate optimal conditions. Secondly, we will use a more exact approach that requires more experiments and uses more advanced simulation- and optimization algorithms

  • 7.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Kaczmarski, Krzysztof
    A systematic investigation on the accuracy of computer simulations for optical isomers in industrial settings2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    Predicting the band profiles of typical chromatographic separations using the approach of the inverse method (IM) [2] requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation [1]. The accuracy of the determination of the competitive adsorption isotherms is therefore explicitly dependent on the choice of algorithm to solve the ED model. Earlier studies have shown that the well known RFD algorithm [3] has limitations in its accuracy for certain simulated conditions such as column efficiency and adsorption isotherm type [5]. In this study, we thoroughly investigate three different algorithms, the rapid and well known Rouchon Finite Difference (RFD) algorithm [3], the Orthogonal Collocation on Finite Elements (OCFE) method [4] and the Central Difference Method (CDM) algorithm developed by us. Firstly, a systematic investigation is made, comparing the different algorithms under a broad range of different synthetic conditions. Secondly, we apply all three algorithms using the IM on real experimental systems; (I) one high efficiency quaternary separation and (II) one pharmaceutical industry application with a chiral intermediate separation. We have found discrepancies between the conventional (RFD) and the more accurate (OCFE and CDM) algorithms for several synthetic conditions such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm but better prediction of OCFE/CDM for a binary low efficiency separation problem. Our conclusion is to use the RFD algorithm with caution when any of the particular conditions we have investigated is valid. When the highest accuracy is sought, there is no doubt that OCFE or CDM should be the algorithms of choice. However, given the computational speed of RFD, we also recommend it for preliminary parameter fitting. For conditions where we have shown the algorithms to produce practically identical solutions, RFD can be applied with greater certainty. It remains to be thoroughly investigated the effect on the particular shape of the adsorption isotherm on the obtained solution, for example type III having inflection points.

  • 8.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Determination of adsorption isotherms in supercritical fluid chromatography2013Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1312, s. 124-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract In this study we will demonstrate the potential of modern integrated commercial analytical SFC-systems for rapid and reliable acquisition of thermodynamic data. This will be done by transferring the following adsorption isotherm determination methods from liquid chromatography (LC) to supercritical fluid chromatography (SFC): Elution by Characteristic Points (ECP), the Retention Time Method (RTM), the Inverse Method (IM) and the Perturbation Peak (PP) method. In order to transfer these methods to SFC in a reliable, reproducible way we will demonstrate that careful system verification using external sensors of mass flow, temperature and pressure are needed first. The adsorption isotherm data generated by the different methods were analyzed and compared and the adsorption isotherms ability to predict new experimental elution profiles was verified by comparing experiments with simulations. It was found that adsorption isotherm data determined based on elution profiles, i.e., ECP, IM and RTM, were able to accurately predict overloaded experimental elution profiles while the more tedious and time-consuming PP method, based on small injections on concentration plateaus, failed in doing so.

  • 9.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörsvetenskap och fysik (from 2013).
    Glenne, Emelie
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Leśko, Marek
    Rzeszów University of Technology, Poland.
    Langborg Weinmann, Annika
    AstraZeneca.
    Leek, Tomas
    AstraZeneca.
    Kaczmarski, Krzysztof
    AstraZeneca.
    Klarqvist, Magnus
    AstraZeneca.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Investigation of robustness for supercritical fluid chromatography separation of peptides: Isocratic vs gradient mode2018Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, s. 177-187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated and compared the robustness of supercritical fluid chromatography (SFC) separations of the peptide gramicidin, using either isocratic or gradient elution. This was done using design of experiments in a design space of co-solvent fraction, water mass fraction in co-solvent, pressure, and temperature. The density of the eluent (CO2-MeOH-H2O) was experimentally determined using a Coriolis mass flow meter to calculate the volumetric flow rate required by the design. For both retention models, the most important factor was the total co-solvent fraction and water mass fraction in co-solvent. Comparing the elution modes, we found that gradient elution was more than three times more robust than isocratic elution. We also observed a relationship between the sensitivity to changes and the gradient steepness and used this to draw general conclusions beyond the studied experimental system. To test the robustness in a practical context, both the isocratic and gradient separations were transferred to another laboratory. The gradient elution was highly reproducible between laboratories, whereas the isocratic system was not. Using measurements of the actual operational conditions (not the set system conditions), the isocratic deviation was quantitatively explained using the retention model. The findings indicate the benefits of using gradient elution in SFC as well as the importance of measuring the actual operational conditions to be able to explain observed differences between laboratories when conducting method transfer.

  • 10.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    A Deeper Understanding of a Complex Adsorption Behavior in a Common Chiral, Separation System2011Konferensbidrag (Refereegranskat)
    Abstract [en]

    The adsorption equilibria of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. This separation has previously been performed and analyzed on a methylcellulose tribenzoate coated CSP. In that case, both enantiomers could be described with a bi-Langmuir adsorption isotherm, convex upwards (type I). In our case, two fundamentally different properties were observed. First, the elution order was reversed. Furthermore, only the less retained enantiomer shows type I adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration. To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.

  • 11.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    A thermodynamic and kinetic study of an unusual adsorption behavior-Methyl Mandelate on commercially available Tris-(3,5- dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase2012Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    The adsorption equilibria of racemic methyl mandelate on a tris-(3,5- dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. The following were observed, the less retained enantiomer shows “Langmuirian” (type I) adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration. To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution (AED) calculations. The less retained enantiomer was best described by heterogeneous unimodal adsorption model (Tóth) while the second enantiomer was best described with a heterogeneous adsorption model with adsorbate-adsorbate interactions (bi-Moreau). The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature. This is an industrial – academic cooperation in the Fundamental Separation Science Group www.separationscience.se

  • 12.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Characterization of the Adsorption of Racemic Methyl Mandelate on Tris-(3,5-dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase2011Konferensbidrag (Refereegranskat)
    Abstract

    The adsorption equilibria of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. This separation has previously been performed and analyzed on a methylcellulose tribenzoate coated CSP. In that case, both enantiomers could be described with a bi-Langmuir adsorption isotherm, convex upwards (type I). In our case, two fundamentally different properties were observed. First, the elution order was reversed. Furthermore, only the less retained enantiomer shows type I adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration.

    To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature.

    Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.

  • 13.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    On the Reproducibility between Different Modern Supercritcal Fluid Chromatographic Systems2013Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Three different, commercially available, Supercritical Fluid Chromatography (SFC) systems were investigated: Thar Super Pure Discovery Series SFC, Waters UPC2 and Agilent 1260 Infinity SFC. The reason for choosing the two analytical systems from Agilent and Waters is that they represent two of the latest commercial systems available while the semi-preparative instrument was added to widen the study to include instruments also used for preparative purposes. With identical operational conditions set these systems were used to acquire analytical retention data and adsorption isotherms from overloaded injections. The investigation was limited to the use of methanol as modifier and operational conditions, temperature and back pressure most typically observed when utilizing SFC to separate polar compounds. The results clearly show that both analytical retention times and elution profiles are system dependent. Since the overloaded elution profiles are system dependent the adsorption isotherm will also be different. However, this do not mean that the adsorption is different, instead this it is due to the fact that identical instrumental settings, especially pressure and modifier composition settings, does not necessarily mean that the conditions inside the column are identical. This means that it is not possible to transfer an established separation method from one system to another, even if one is using the same column and identical instrument settings. Understanding of SFC-systems will be of fundamental importance for successful transfer of methods between systems, reliable adsorption isotherm determination, and analytical quality work and scaling up from analytical to preparative mode. These issues can probably be solved by measuring mass flow, pressure and temperature along the column, together with a sound understanding of the density variations of the mobile phase. However, the work of finding acceptable applications or guidelines to remove the tedious need for these measurements is currently investigated in our lab. This is a contribution from the Fundamental Separation Science Group www.FSSG.se

  • 14.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Using Modern SFC Systems for Adsorption Characterization2013Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Recently the pharmaceutical industry has started to replace preparative HPLC with preparative SFC to lower the environmental impact and to increase performance. Reliable characterization of the adsorption processes in SFC is therefore of utmost importance. The key thermodynamic phase system information is obtained by rigorous determination of adsorption isotherm data over a broad concentration range. If properly processed, this data gives not only correct information about the degree of heterogeneity but also the energy of interactions and mono layer capacities of each individual type of adsorption site in the phase system. Ultimately, this can result in identification of the types of interactions, i.e., dipole-dipole, van der Waals interactions etc. In this study we will present transfer of selected adsorption characterization methods, traditionally applied with success in LC, to SFC. We have here transferred all available knowledge from LC – from model selection to validation. We will also, using recent findings, explain the effects of pressure and temperature variations as well as how to accurately measure the volumetric flow rate on a modern analytical SFC system. We will demonstrate how the latest SFC instruments, with some critical modifications; have the potential for rapid and reliable acquisition of thermodynamic data using the ECP method. Finally we will elaborate on how the adsorption depends on density, temperature and modifier content in the mobile phase. This is a contribution from the Fundamental Separation Science Group www.FSSG.se

  • 15.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Preparative Separation of Chiral Pharmaceutical Compounds - The Effects of Packing Particle Size, Pressure Limit and Column Geometry on Productivity and Solvent Consumption2011Konferensbidrag (Refereegranskat)
    Abstract [en]

    In this study, omeprazole was used as a model compound. Omeprazole and other related sulfoxidebenzimidazolesare used against gastric ulcersand have been extensively studied regarding chromatographic resolution techniques using several different chiral stationary phases.First, AstraZeneca launched Losec, a racemic mixture of RS-omeprazole. Facing loss of patent, the more potent S-enantiomer was developed and marketed as Nexium. Now the patent of Nexium is close expiration why methods for isolation of the pure S-enantiomer will be of importance for the generic pharmaceutical companies.The experimental model separation system represents a system with good selectivity and high solubility of the solute in the eluent. In this investigation the productivity optima for three different particle sizes (5, 10 and 25 µm) at maximum system pressure ranging from 50 to 400 bars are studied. Two different optimizations cases were studied in depth. First,a process optimization with fixed column geometry is studied. The results clearly show that larger packing materials have higher productivity at low pressure drops on the analytical size column.With increasing allowed pressure drops, over 200 bar, the smaller packing materials have substantially higher productivity. The results also show that smaller packing material will always have much lower solvent consumption compared to larger particles.The second process optimization was performed with a fixed column volume, but the column geometry was variable. The results shows that the productivity obtained for the smaller packing particles materials was higher compared to the large for all allowed pressure drops. The productivity obtained for the small particle compared to the large increased by 25-300 % while maintaining 50-300 % less solvent consumption for the purification of the first enantiomer.The addition of TEA seems to be unfavorable for all tested conditions.In conclusion, the optimization of the enantioseparation of omeprazole has been shown to be dependent on column packing particle size as well as column geometry. It has been demonstrated that all parameters need to be simultaneously optimized to reach a global productivity optima.

  • 16.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Preparative Separation of Omeprazole: Predictions of the Optimal Experimental Conditions by Computer Simulations2011Konferensbidrag (Refereegranskat)
    Abstract [en]

    In this study, omeprazole was used as a model compound. Omeprazole and other related sulfoxide benzimidazoles are used against gastric ulcers and have been extensively studied regarding chromatographic resolution techniques using several different chiral stationary phases.First, AstraZeneca launched Losec, a racemic mixture of RS-omeprazole. Facing loss of patent, the more potent S-enantiomer was developed and marketed as Nexium. Now the patent of Nexium is close expiration why methods for isolation of the pure S-enantiomer will be of importance for the generic pharmaceutical companies.The experimental model separation system represents a system with good selectivity and high solubility of the solute in the eluent. In this investigation the productivity optima for three different particle sizes (5, 10 and 25 µm) at maximum system pressure ranging from 50 to 400 bars are studied. Two different optimizations cases were studied in depth. First,a process optimization with fixed column geometry is studied. The results clearly show that larger packing materials have higher productivity at low pressure drops on the analytical size column.With increasing allowed pressure drops, over 200 bar, the smaller packing materials have substantially higher productivity.The results also show that smaller packing material will always have much lower solvent consumption compared to larger particles.The second process optimization was performed with a fixed column volume, but the column geometry was variable. The results shows that the productivity obtained for the smaller packing particles materials was higher compared to the large for all allowed pressure drops. The productivity obtained for the small particle compared to the large increased by 25-300 % while maintaining 50-300 % less solvent consumption for the purification of the first enantiomer.The addition of TEA seems to be unfavorable for all tested conditions.In conclusion, the optimization of the enantioseparation of omeprazole has been shown to be dependent on column packing particle size as well as column geometry. It has been demonstrated that all parameters need to be simultaneously optimized to reach a global productivity optima.

  • 17.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Undin, Torgny
    A Deeper Investigation of Strange Preparative Band Shapes of a Simple Racemic Solute on tris-(3, 5- dimethylphenyl)carbamoyl Cellulose as Chiral Stationary Phase2011Konferensbidrag (Refereegranskat)
    Abstract

    The adsorption equilibria of racemic methyl mandelate on a tris-(3, 5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) has a peculiar behavior. The preparative band shape of the more retained enantiomer was very unusual with an inflection point at low concentrations whereas the less retained enantiomer shows normal type I adsorption behavior. For a deeper understanding of this separation adsorption isotherms were determined and further analyzed with Scatchard plots combined with adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-ideal adsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature

  • 18.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Forss, Erik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography2014Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1354, s. 129-138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Perturbation Peak (PP) method and Frontal analysis (FA) are considered as the most accurate methods for adsorption isotherms determination in liquid chromatography. In this study we investigate and explain why this is not the case in Supercritical Fluid Chromatography (SFC), where the PP method does not work at all, using a modern analytical system. The main reason was found to be that the solute to be studied must be dissolved in the MeOH reservoir before it is mixed with CO2. Since the solute occupies a certain partial volume in the reservoir, the larger the solute content the larger this fractional volume will be, and the final MeOH fraction in the mobile phase will then be smaller compared to the bulk mobile phase without solute in the modifier. If the retention of small injections on the concentration plateaus, i.e., “analytical-size” perturbation peaks, is sensitive to small variations of MeOH in the eluent, this will seriously decrease the accuracy of the PP method. This effect was verified and compensated for and we also demonstrated that the same problem will occur in frontal analysis, another concentration plateau method.

  • 19.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Enantioseparation of omeprazole effect of different packing particle size on productivity2012Ingår i: Journal of Chromatography A, ISSN 0021-9673, Vol. 1240, nr 1, s. 123-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enantiomeric separation of omeprazole has been extensively studied regarding both product analysis and preparation using several different chiral stationary phases. In this study, the preparative chiral separation of omeprazole is optimized for productivity using three different columns packed with amylose tris (3,5-dimethyl phenyl carbamate) coated macroporous silica (5, 10 and 25 Όm) with a maximum allowed pressure drop ranging from 50 to 400 bar. This pressure range both covers low pressure process systems (50–100 bar) and investigates the potential for allowing higher pressure limits in preparative applications in a future. The process optimization clearly show that the larger 25 Όm packing material show higher productivity at low pressure drops whereas with increasing pressure drops the smaller packing materials have substantially higher productivity. Interestingly, at all pressure drops, the smaller packing material result in lower solvent consumption (L solvent/kg product); the higher the accepted pressure drop, the larger the gain in reduced solvent consumption. The experimental adsorption isotherms were not identical for the different packing material sizes; therefore all calculations were recalculated and reevaluated assuming identical adsorption isotherms (with the 10 Όm isotherm as reference) which confirmed the trends regarding productivity and solvent consumption.

  • 20.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Högblom, Joakim
    Eka Chemicals.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Adsorption Isotherm Determination for Reliable Phase System Characterization in SFC: Challenges and Pitfalls2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    Recently the pharmaceutical industry has started to replace HPLC with SFC because of incentives to lower the environmental impact and as well as increasing performance. Reliable characterization of the adsorption processes in SFC, is therefore of utmost importance. The key thermodynamic phase system information is obtained by rigorous determination of adsorption isotherms over a broad concentration range. If properly processed, this data gives not only correct information about the degree of heterogeneity but also the values of the energy of interactions and monolayer capacities of each individual type of adsorption site in the phase system; ultimately, this can result in identification of the types of interactions (dipole-dipole, van der Waals interactions etc.). In this study, we will present the transfer of LC adsorption characterization methods to SFC conditions using several model compounds with several different methods for adsorption isotherm determination traditionally applied with success in LC, and now modified for SFC. We have limited our investigation to methanol as modifier and used the operational conditions, temperature and backpressure most typically observed in industrial settings; in addition, we have used commercial standard SFC-equipment. The results clearly shows that adsorption isotherm determinations in SFC are considerably more complicated than in LC; we will go through the most important pitfalls and give guidelines for more rigorous determinations of adsorption data in SFC. This is an industrial – academic cooperation in the Fundamental Separation Science Group www.separationscience.se

  • 21.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Undin, Torgny
    Uppsala University Analytisk Kemi.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Characterization of an unusual adsorption behavior of racemic methyl-mandelate on a tris-(3,5-dimethylphenyl) carbamoyl cellulose chiral stationary phase2011Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, nr 38, s. 6688-6696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An interesting adsorption behavior of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase was theoretically and experimentally investigated. The overloaded band of the more retained enantiomer had a peculiar shape indicating a type V adsorption isotherm whereas the overloaded band of the less retained enantiomer had a normal shape indicating a type I adsorption behavior. For a closer characterization of this separation, adsorption isotherms were determined and analyzed using an approach were Scatchard plots and adsorption energy distribution (AED) calculations are combined for a deeper analysis. It was found that the less retained enantiomer was best described by a Tóth adsorption isotherm while the second one was best described with a bi-Moreau adsorption isotherm. The latter model comprises non-ideal adsorbate–adsorbate interactions, providing an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated using synthetically generated raw adsorption slope data. It was found that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and found to be exothermic; i.e. the adsorbate–adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process revealed that the average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.

  • 22.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Åsberg, Dennis
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    The Effect of Temperature, Pressure and Co-Solvent on a Chiral Supercritical Fluid Chromatography Separation2014Ingår i: Chromatography Today, ISSN 1752-8070, Vol. 7, nr 3, s. 14-17Artikel i tidskrift (Refereegranskat)
  • 23.
    Enmark, Martin
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Åsberg, Dennis
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Shalliker, Andrew
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    A closer study of peak distortions in supercritical fluid chromatography as generated by the injection2015Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1400, s. 131-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract In SFC the sample cannot be dissolved in the mobile phase, so it is often dissolved in pure modifier, or another liquid, sometimes resulting in serious distortions of the eluted peak profiles already at moderately high injection volumes. It is suspected the reasons for these effects are solvent strength mismatch and/or viscosity mismatch. This study presents a systematic and fundamental investigation of the origin of these peak deformations due to the injection solvent effects in SFC, using both systematic experiments and numerical modeling. The first set of experiments proved that the injection volume and the elution strength of the sample solution had a major impact of the shapes of the eluted peaks. Secondly, the sample band elution profile was numerically modeled on a theoretical basis assuming both un-retained and retained co-solvent injection plugs, respectively. These calculations quantitatively confirmed our first set of experiments but also pointed out that there is also an additional significant effect. Third, viscous fingering experiments were performed using viscosity contrast conditions imitating those encountered in SFC. These experiments clearly proved that viscous fingering effects play a significant role. A new method for determination of adsorption isotherms of solvents was also developed, called the “Retention Time Peak Method” (RTPM). The RTPM was used for fast estimation of the adsorption isotherms of the modifier and required using only two experiments.

  • 24.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Modeling of Preparative Liquid Chromatography2013Ingår i: Liquid Chromatography: Fundamentals and Instrumentation / [ed] Salvatore Fanali, Paul R. Haddad; Poole, Colin; Schoenmakers, Peter; Lloyd, David K., Elsevier, 2013, s. 407-425Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Abstract Preparative chromatography is today the best generic method for the purification of small drugs and valuable chemical components at the <10 kg-level. Recent progress in computer technology and the development of new nonchiral and chiral stationary phases, as well as numerous improvements in reliability and economic performance, have considerably increased the interest in modeling in academic and industrial communities. This chapter serves as an introduction to the field of modeling preparative liquid chromatography in the classical batch mode, aiming at improved process purification of valuable chemical components, drugs, and chiral components. We go through the most important column and adsorption models and methods for determination of the essential thermodynamic adsorption data for both column characterization and process improvement. But, we also cover important operational conditions sometimes neglected in the modeling procedure, such as the impact of injection profiles and accounting for the additive in the modeling procedure.

  • 25.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    A more reliable procedure for estimating interactions between drugs and biomolecules using biosensors: a comparison with chromatography2012Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    This poster serves as background information to the corresponding lecture. Adsorption isotherms are essential in order to understand the interaction between small molecules such as pharmaceutical compounds and larger biomolecules. An adsorption isotherm describes the relationship of free substance in a solution with adsorbed substance to a surface, at a specific and constant temperature. Adsorption isotherms could be determined using several different method, all method have their pros and cons. In this study we are using two modern but principally different biosensors to determine interactions: quarts micro-balance (QCM) and Surface plasmon resonance (SPR) to determine interactions. For a long time adsorption isotherms has been determined solely by the chromatographic community. In this study we will present transformation of adsorption analysis tools from chromatography to biosensors, especially calculation of adsorption energy distribution prior adsorption model fit. We will also discuss how the experiments should be conducted. Guidelines will be given for the experimental setup and for when the chromatographic or a biosensor technique is to be preferred. This is a contribution from the Fundamental Separation Science Group in Karlstad www.separationscience.se

  • 26.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Determination of adsorption processes in modern chromatographic systems - Characterization, illustrations and guidlines how to avoid common pitfalls2010Konferensbidrag (Refereegranskat)
  • 27.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Insights into retention mechanisms and bio-molecular interactions gained from rigorous evaluation of adsorption data derived from HPLC and modern biosensors2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    The estimation of reliable adsorption / equilibrium data are crucial for researchers in a wide range of fields such as analytical chemistry, biochemistry, chemical engineering, pharmacology and pharmacokinetics. Traditionally, equilibrium data are simply estimated from the statistically best-fitted model to adsorption data; but there are many dangerous pitfalls on this road. We have therefore recently improved several methods for adsorption isotherm determinations. As example, the accuracy of generating adsorption data by the elution by characteristic points (ECP) method was increased considerably by a new experimental approach that eliminated the post-loop dispersion; the method was also expanded to cover more different general types of adsorption isotherms than before. We have also made important improvements on the processing and evaluation of the data based on a firm theoretical basis. In this context, a new numerical tool was developed, calculation of the adsorption energy distribution (AED) allowing the estimation of the degree of heterogeneity of the interaction prior to the rival model fit. This concept has also been transposed to modern biosensors such as surface plasmon resonance (SPR) technology and continuous flow quartz crystal microbalance (QCM). We have utilized the improvements of generating and evaluation adsorption data to reveal more detailed information about molecular interactions in systems aimed at analytical and preparative separations and to understand better bio-molecular interactions derived from modern biosensors. This is a contribution from the Fundamental Separation Science Group in Karlstad www.separationscience.se

  • 28.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    The Tracer-pulse Experience €œ"reveiling the invisible iceberg"2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    This Poster gives complementary material to the Lecture “Visualization of Chromatographic Surprises – The Helfferich Paradox Revisited. Here we will give more information on the remarkable deformations of invisible zones in the most simple and chromatographic system, unknown for most chromatographer. It is like reviling the part of the iceberg that is invisible, under the water.We recently described that “the injected sample molecules are not always found in the peak”. This happens if a small excess of molecules is injected into a column equilibrated with the same kind of molecules. Only one single peak will appear on the chromatogram (the system peak) while the injected molecules elute later in an invisible zone. The latter zones can be visualized by smart, but tedious, experimental procedures using either tracers or enantiomers. The phenomenon which was predicted by Helfferich in Science around 40 years ago was recently experimentally proven by us for the first time.As we continued to investigate the phenomena we could see that invisible zones containing the injected molecules take on the most strange and deformed shapes at higher sample loads. We will further show that a similar type of phenomenon appears in frontal analysis which results in invisible break-through and desorption curves. Depending on the conditions, the invisible breakthrough curves become more or less deformed. We explain the effects with the help of computer simulations which show an excellent agreement with experimental profiles of peaks and fronts.

    Single component, small perturbation

    Experimental Proof of a Chromatographic Paradox: Are the Injected Molecules in the Peak? Jörgen Samuelsson, Patrik Forsén, Morgan Stefansson and Torgny Fornstedt. Analytical Chemistry 2004, 76(4). 953-958.

    Single component, large perturbation

    Invisible Analyte Peak Deformations in Single-Component Liquid Chromatography” by Jörgen Samuelsson, Robert Arnell and Torgny Fornstedt. Analytical Chemistry (2006) 78 2765-2771.

    Single component, frontal analysis

    Discovery of invisible extra fronts in single-component frontal analysis in liquid chromatography by Jörgen Samuelsson and Torgny Fornstedt. Journal of Chromatography A (2006) 1114, 53-61.

    Multi-component, small perturbation

    Validation of the Tracer Pulse Method for Multi Component Liquid Chromatography- a Classical Paradox Revisited. Robert Arnell and Torgny Fornstedt. Analytical Chemistry (2006) 78, 4615-4623.

  • 29.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Visualization of Chromatographic Surprises - The Helfferich Paradox Revisited2011Övrigt (Övrigt vetenskapligt)
  • 30.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    A systematic investigation of deformations of overloaded peak shapes of basic compounds in reversed phase chromatography2010Konferensbidrag (Refereegranskat)
  • 31.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    Deformations of overloaded bands under pH-stable conditions in reversed phase chromatography2011Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, nr 15, s. 1966-1973Artikel i tidskrift (Refereegranskat)
    Abstract

    It has recently been demonstrated, using mathematical models, how peculiar overloaded band profiles of basic compounds are due to the local pH in the column when using low capacity buffers. In this study, overloaded peak shapes resulting after injection of carefully pH matched samples close to the pKa of the chosen solute are investigated primarily on two columns; one hybrid silica C18 column (Kromasil Eternity) and one purely polymeric column (PLRP-S), the latter lacking C18 ligands. It was found that distorted peaks of the basic test compound appear even though there is no difference in pH between the injected sample solution and the eluent; the previous explanation to why these effects occur is based on a pH mismatch. Thus, the unusual band shapes are not due to an initial pH difference. Furthermore, it was observed that the effect does not appear on polymeric columns without C18 ligands, but only on columns with C18 ligands, independently of the base matrix (silica, hybrid silica, polymeric)

  • 32.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    Peak Deformations of Basic Compounds in Reversed Phase Chromatography Under pH-stable conditions2010Konferensbidrag (Refereegranskat)
  • 33.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    Department of Physical and Analytical Chemistry, Uppsala University.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Injection profiles in liquid chromatography. I. A fundamental investigation2010Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, nr 26, s. 4306-4312Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This is a fundamental experimental and theoretical investigation on how the injection profile depends on important experimental parameters. The experiments revealed that the injection profile becomes more eroded with increased (i) flow rate, (ii) viscosity of the eluent, (iii) size of the solute, (iv) injection volume and (v) inner diameter of the injection loop capillary. These observations cannot be explained by a 1D-convection-diffusion equation, since it does not account for the effect of the parabolic flow and the radial diffusion on the elution profile. Therefore, the 1D model was expanded into a 2D-convection-diffusion equation with cylindrical coordinates, a model that showed a good agreement with the experimental injection profiles dependence on the experimental parameters. For a deeper understanding of the appearance of the injection profile the 2D model is excellent, but to account for injection profiles of various injection volumes and flow rates in preparative and process-chromatography using computer-optimizations, a more pragmatic approach must be developed. The result will give guidelines about how to reduce the extra-column variance caused by the injection profile. This is important both for preparative and analytical chromatography; in particular for modern analytical systems using short and narrow columns

  • 34.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Transposing Advanced LC Theory to Modern Biosensors - Estimation of Bio-Molecular Interactions and Drug-Protein Interactions by Transposing LC-Theory to Biosensors2012Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    This poster will also serves as background information to the lecture “Deeper insights in retention mechanisms and molecular interactions through improved methods for generating and evaluation adsorption data”. Adsorption isotherms are essential in order to understand the interaction between small molecules such as pharmaceutical compounds and larger biomolecules. An adsorption isotherm describes the relationship of free substance in a solution with adsorbed substance to a surface, at a specific and constant temperature. Adsorption isotherms could be determined using several different method, all method have their pros and cons. In this study we are using two modern but principally different biosensors to determine interactions: quarts micro-balance (QCM) and Surface plasmon resonance (SPR) to determine interactions. For a long time adsorption isotherms has been determined solely by the chromatographic community. In this study we will present transformation of adsorption analysis tools from chromatography to biosensors, especially calculation of adsorption energy distribution prior adsorption model fit. We will also discuss how the experiments should be conducted. Guidelines will be given for the experimental setup and for when the chromatographic or a biosensor technique is to be preferred. This is a contribution from the Fundamental Separation Science Group in Karlstad www.separationscience.se

  • 35.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Undin, Torgny
    Petersson, Patrik
    Törncrona, Anders
    Ekeroth,, Johan
    A New Approach for Characterization of Adsorption Processes in Analytical Chromatographic Systems by Combining Linear and Nonlinear Methods2010Konferensbidrag (Refereegranskat)
  • 36.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Undin, Torgny
    Törncrona,, Anders
    Deeper characterization of new hybrid silica phases - A combined experimental and theoretical approach2010Konferensbidrag (Refereegranskat)
  • 37.
    Fornstedt, Torgny
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Åsberg, Dennis
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Lesko, Marek
    Rzeszow University of Technology.
    Enmark, Martin
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörsvetenskap och fysik.
    Forssén, Patrik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Kaczmarski, Krzysztof
    Rzeszow University of Technology.
    New Procedure for Predictions of Overloaded Profiles in Gradient Elution2013Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    To simulate the separation process in liquid chromatography, the competitive adsorption isotherms need to be known. In gradient elution, the adsorption isotherms are determined with isocratic experiments on different mobile-phase plateaus, levels covering the range used in the gradient program. This can lead to extreme retention times for some mobile-phase compositions and therefore it might even be impossible to determine all necessary adsorption data using the traditional isocratic approach. In this talk, we will present a method where single and competitive nonlinear adsorption isotherms are determined directly from overloaded elution profiles in gradient elution. The numerical coefficients in the adsorption isotherms are determined by the inverse method that minimizes the difference between calculated and experimental elution profiles. This is a new method where the need for tedious/impossible isocratic experiments is eliminated. The method is systematically verified using both synthetic and experimental data. Finally the new method is used to successfully predict elution profiles for a two-component mixture in gradient elution. The new method open up the opportunity to study the adsorption of substances whose retention factor vary strongly with the mobile-phase composition, like peptides and proteins, where the classic methods will fail. We also intend to transfer the metholology for SFC in near future; but there are some problems to be solved first (see our SFC posters). This is a contribution from the Fundamental Separation Science Group www.FSSG.se

  • 38.
    Forssén, Patrik
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    Uppsala University.
    Lämmerhofer, Michael
    Institute of Pharmaceutical Sciences, University of Tübingen, Germany.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Karlsson, Anders
    Department of Molecular Biology, Göteborg University .
    Lindner, Wolfgang
    Department of Analytical Chemistry, University of Vienna, Austria.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap. Uppsalas universitet.
    Optimization strategies accounting for the additive in preparative chiral liquid chromatography2012Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1269, s. 279-286, artikel-id SIArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study is an in-depth investigation on how numerical optimization strategies that also account forthe additive type and concentration, in preparative batch chromatography, should be performed. As amodel system, the separation of Z-(R,S)-2-aminobutyric acid enantiomers on a quinidine carbamate-based chiral stationary phase in polar organic mode was used, with different additive strengths of aceticacid or hexanoic acid in methanol. The inverse method was used to determine the competitive adsorp-tion isotherm parameters for the enantiomers and the additives. Three different optimization strategieswere examined: (1) injection volume optimization, (2) optimization of injection volume and additiveconcentration, and (3) full optimization including injection volume, additive concentration, sample con-centration and flow rate. It was concluded that (i) it is important to incorporate the additive concentrationin the optimization procedure to achieve the highest production rates, (ii) the full optimization strategyhad the overall best results, and (iii) the selection of additive is very important (here acetic acid additivewas superior to the hexanoic acid additive). By including the additive in the adsorption model and inthe numerical optimization it is not only possible to achieve higher production rates but also to properlyselect the additive that is most advantageous for the specific separation problem.

  • 39.
    Forssén, Patrik
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Edström, Lena
    Uppsala University.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Injection profiles in liquid chromatography II: Predicting accurate injection-profiles for computer-assisted preparative optimizations2011Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, nr 34, s. 5794-5800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In computer assisted optimization of liquid chromatography it has been known for some years that it is important to use experimental injection profiles, instead of rectangular ones, in order to calculate accurate elution bands. However, the incorrectly assumed rectangular profiles are still mostly used especially in numerical optimizations. The reason is that the acquisition of injection profiles, for each injection volume and each flow rate considered in a computer-assisted optimization requires a too large number of experiments. In this article a new function is proposed, which enables highly accurate predictions of the injection profiles and thus more accurate computer optimizations, with a minimum experimental effort. To model the injection profiles for any injection volume at a constant flow rate, as few as two experimental injection profiles are required. If it is desirable to also take the effect of flow rate on the injection profiles into account, then just two additional experiments are required. The overlap between fitted and experimental injection profiles at different flow rates and different injection volumes were excellent, more than 90%, using experimental injection profiles from just four different injection volumes at two different flow rates. Moreover, it was demonstrated that the flow rate has a minor influence on the injection profiles and that the injection volume is the main parameter that needs to be accounted for.

  • 40.
    Forssén, Patrik
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Multia, Evgen
    University of Helsinki, Finland.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Andersson, Marie
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Aastrup, Teodor
    Attana AB, Sweden.
    Altun, Samuel
    Attana AB, Sweden.
    Wallinder, Daniel
    Attana AB, Sweden.
    Wallbing, Linus
    Attana AB, Sweden.
    Liangsupree, Thanaporn
    University of Helsinki, Finland.
    Riekkola, Marja-Liisa
    University of Helsinki, Finland.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Reliable Strategy for Analysis of Complex Biosensor Data2018Ingår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, nr 8, s. 5366-5374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.

  • 41.
    Forssén, Patrik
    et al.
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap.
    Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography. I: Investigation of a chiral separation system2013Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1299, s. 58-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Starting out from an experimental chiral separation system we have used computer simulations for a systematic investigation on how the maximum productivity depends on changes in column length, packing particle size, column efficiency, back pressure, sample concentration/solubility, selectivity, retention factor of the first eluting component and monolayer saturation capacity. The study was performed by changing these parameters, one at a time, and then calculating the corresponding change in maximum productivity. The three most important parameters for maximum production rate was found to be (i) the selectivity (ii) the retention factor of the first eluting component and (iii) the column length. Surprisingly, the column efficiency and sample concentration/solubility were of minor importance. These findings can be used as rough guidelines for column selection, e.g. a low-efficiency column are more likely perform better, in terms of productivity, than a high-efficiency column that have higher retention factor for the first eluting component.

  • 42.
    Forssén, Patrik
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography II: Investigation of separation systems with competitive Langmuir adsorption isotherms2014Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1347, s. 72-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study we investigated how the maximum productivity for commonly used, realistic separation system with a competitive Langmuir adsorption isotherm is affected by changes in column length, packing particle size, mobile phase viscosity, maximum allowed column pressure, column efficiency, sample concentration/solubility, selectivity, monolayer saturation capacity and retention factor of the first eluting compound. The study was performed by generating 1000 random separation systems whose optimal injection volume was determined, i.e., the injection volume that gives the largest achievable productivity. The relative changes in largest achievable productivity when one of the parameters above changes was then studied for each system and the productivity changes for all systems were presented as distributions. We found that it is almost always beneficial to use shorter columns with high pressure drops over the column and that the selectivity should be greater than 2. However, the sample concentration and column efficiency have very limited effect on the maximum productivity. The effect of packing particle size depends on the flow rate limiting factor. If the pumps maximum flow rate is the limiting factor use smaller packing, but if the pressure of the system is the limiting factor use larger packing up to about 40μm.

  • 43.
    Fredriksson, Robert
    et al.
    AkzoNobel , Separations Products, Bohus, Sweden.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    The Importance of Overloading Studies in Method Development: A Case Study2012Konferensbidrag (Refereegranskat)
  • 44.
    Friden, Mikael E.
    et al.
    Uppsala Univ, Dept Chem BMC, Analyt Chem, POB 599, S-75124 Uppsala, Sweden..
    Jumaah, Firas
    Lund Univ, Ctr Anal & Synth, Dept Chem, POB 124, S-22100 Lund, Sweden..
    Gustavsson, Christer
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Enmark, Martin
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Turner, Charlotta
    Lund Univ, Ctr Anal & Synth, Dept Chem, POB 124, S-22100 Lund, Sweden..
    Sjoberg, Per J. R.
    Uppsala Univ, Dept Chem BMC, Analyt Chem, POB 599, S-75124 Uppsala, Sweden..
    Samuelsson, Jorgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Evaluation and analysis of environmentally sustainable methodologies for extraction of betulin from birch bark with a focus on industrial feasibility2016Ingår i: Green Chemistry, ISSN 1463-9262, E-ISSN 1463-9270, Vol. 18, nr 2, s. 516-523Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Betulin from birch bark was extracted using two principally different extraction methodologies - classical Reflux Boiling (RB) and Pressurized Liquid Extraction (PLE). The extraction methods were analyzed based on both recovery and purity as well as for RB industrial feasibility. The purity and recovery for the different extraction methods were analyzed using High Performance Liquid Chromatography (HPLC) coupled with three different detection principles: Diode Array Detection (DAD), Mass Spectrometry (MS) and Charged Aerosol Detection (CAD). The chromatographic purity was determined by all detections whereas the DAD was used also for complementary gravimetric calculations of the purity of the extracts. The MS detection (in MS and MS/MS modes) was mainly used to characterize the impurities. Two steps to increase the purity of RB extracts were evaluated - pre-boiling the bark in water and precipitation by adding water to the extract. Finally, the methods were compared in terms of amounts of betulin produced and solvent consumed. The RB method including a precipitation step produced the highest purity of betulin. However, results indicate that PLE using three cycles with the precipitation step gives similar purities as for RB. The PLE method produced up to 1.6 times higher amount of extract compared to the RB method. However, the solvent consumption (liter solvent per gram product) for PLE was around 4.5 times higher as compared to the classical RB. PLE performed with only one extraction cycle gave results more similar to RB with 1.2 times higher yield and 1.4 times higher solvent consumption. The RB process was investigated on an industrial scale using a model approach and several important key-factors could be identified. The most energy demanding step was the recycling of extraction solvent which motivates that solvent consumption should be kept low and calculations show a great putative energy reduction by decreasing the ethanol concentration used in the RB process to lower than 90%.

  • 45.
    Glenne, Emelie
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Leek, Hanna
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, Jorgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Peak deformations in preparative supercritical fluid chromatography due to co-solvent adsorption2016Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1468, s. 200-208Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In supercritical fluid chromatography (SFC) the mobile phase comprises of carbon dioxide (CO2) as main solvent and smaller amounts of an organic polar solvent (often an alcohol) as co-solvent. The co-solvent is considered to function by changing the overall polarity of the eluent, i.e. by acting as a "modifier". However, recent studies indicate that the co-solvent methanol can also adsorb to some common SFC stationary phases. Hence, the co-solvent should also be able to function as an "adsorbing additive", i.e. an eluent component that competes with the injected solutes about the stationary phase surface. In this study it was found by fitting different mechanistic models to systematic experimental data, that the co-solvent methanol can have both functions: at low co-solvent fractions, methanol acts as an additive whereas at larger fractions it acts as a modifier. Moreover, it was found that when the co-solvent adsorbs more strongly to the stationary phase than the solute, "bizarre" deformations of the preparative band shapes can occur. This is illustrated by a solute that converts from a normal "Langmuirian" band shape to an "anti-Langmuirian" shape when changing from neat carbon dioxide (CO2) to an eluent containing co-solvent. This peak shape transition is dependent on both (i) the relative retention of the solute and co-solvent to the stationary phase in eluent containing neat CO2 and on (ii) the relative retention of the additive perturbation peak and the solute peak in eluent containing also co-solvent. 

  • 46.
    Glenne, Emelie
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Leek, Hanna
    AstraZeneca R&D, Innovat Med & Early Dev, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med & Early Dev, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Systematic investigations of peak deformations due to co-solvent adsorption in preparative supercritical fluid chromatography2017Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1496, s. 141-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Strangely shaped overloaded bands were recently reported using a standard supercritical fluid chromatographic system comprising a diol column as the stationary phase and carbon dioxide with methanol as the mobile phase, Some of these overloaded elution profiles appeared strongly deformed and even had "anti-Langmuirian" shapes although their solute compounds had "Langmuirian" adsorption. To obtain a more complete understanding of the generality of these effects, the investigation was expanded to cover also other common co-solvents, such as ethanol, 2-propanol, and acetonitrile, as well as various stationary phase materials, such as silica, and 2-ethylpyridine. From this expanded study it could be confirmed that the effects of deformed overloaded solute band shapes, due to co-solvent adsorption, is general phenomena in supercritical fluid chromatographic. It could also be concluded that these effects as well as previously observed "solvent effects" or "plug effects" are entirely due to competition between the solute and solvent molecules for the adsorption sites on the stationary phase surface. Finally, guidelines were given for how to evaluate the risk of deformations occurring for a given solvent-column combination, based simply on testing retention times of solutes and co-solvent. (C) 2017 Elsevier B.V. All rights reserved.

  • 47.
    Glenne, Emelie
    et al.
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Ohlen, Kristina
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Leek, Hanna
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, Jorgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    A closer study of methanol adsorption and its impact on solute retentions in supercritical fluid chromatography2016Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1442, s. 129-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surface excess adsorption isotherms of methanol on a diol silica adsorbent were measured in supercritical fluid chromatography (SFC) using a mixture of methanol and carbon dioxide as mobile phase. The tracer pulse method was used with deuterium labeled methanol as solute and the tracer peaks were detected using APCI-MS over the whole composition range from neat carbon dioxide to neat methanol. The results indicate that a monolayer (4 angstrom) of methanol is formed on the stationary phase. Moreover, the importance of using the set or the actual methanol fractions and volumetric flows in SFC was investigated by measuring the mass flow respective pressure and by calculations of the actual volume fraction of methanol. The result revealed a significant difference between the value set and the actually delivered volumetric methanol flow rate, especially at low modifier fractions. If relying only on the set methanol fraction in the calculations, the Methanol layer thickness should in this system be highly overestimated. Finally, retention times for a set of solutes were measured and related to the findings summarized above concerning methanol adsorption. A strongly non-linear relationship between the logarithms of the retention factors and the modifier fraction in the mobile phase was revealed, prior to the established monolayer. At modifier fractions above that required for establishment of the methanol monolayer, this relationship turns linear which explains why the solute retention factors are less sensitive to changes in modifier content in this region.

  • 48.
    Hernandez, Victor Agmo
    et al.
    Uppsala University, Sweden.
    Samuelsson, Jorgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Forssen, Patrik
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper. Uppsala University, Sweden.
    Enhanced interpretation of adsorption data generated by liquid chromatography and by modern biosensors2013Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, s. 22-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study we demonstrate the importance of proper data processing in adsorption isotherm estimations. This was done by investigating and reprocessing data from five cases on two closely related platforms: liquid chromatography (LC) and biosensors. The previously acquired adsorption data were reevaluated and reprocessed using a three-step numerical procedure: (i) preprocessing of adsorption data, (ii) adsorption data analysis and (iii) final rival model fit. For each case, we will discuss what we really measure and what additional information can be obtained by numerical processing of the data. These cases clearly demonstrate that numerical processing of LC and biosensor data can be used to gain deeper understanding of molecular interactions with adsorption media. This is important because adsorption data, especially from biosensors, is often processed using old and simplified methods. (C) 2013 Elsevier B.V. All rights reserved.

  • 49.
    Hillerström, Anna
    et al.
    Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden.
    Andersson, Martin
    Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden.
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    van Stam, Jan
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper.
    Solvent strategies for loading and release in mesoporous silica2014Ingår i: Colloid and Interface Science Communications, ISSN 2215-0382, Vol. 3, s. 5-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A model molecule, ibuprofen, was loaded in the pores of mesoporous silica by adsorption from nonpolar solvents (liquid carbon dioxide and cyclohexane) and from a polar solvent (methanol). It was sufficient with a very low concentration of ibuprofen in the nonpolar solvents to achieve maximum loading of ibuprofen in the mesoporous particles. When using liquid carbon dioxide, the pores of the mesoporous silica particles were filled completely with ibuprofen at a lower ibuprofen concentration than similar experiments performed with cyclohexane. When methanol was used, the maximum amount of loaded ibuprofen was never achieved. Furthermore, x-ray scattering showed that all ibuprofen loaded into the mesoporous particles were in an amorphous state. Ibuprofen was released from the mesoporous particles to water within a couple of minutes, regardless of solvent used for loading. It was found that the release of ibuprofen from mesoporous silica was much faster than that of crystalline ibuprofen.

  • 50.
    Lesko, Marek
    et al.
    Rzeszów University of Technology, Poland.
    Åsberg, Dennis
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Enmark, Martin
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Samuelsson, Jörgen
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Fornstedt, Torgny
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).
    Kaczmarski, Krzysztof
    Poland.
    Choice of Model for Estimation of Adsorption Isotherm Parameters in Gradient Elution Preparative Liquid Chromatography2015Ingår i: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 78, nr 19-20, s. 1293-1297Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The inverse method is a numerical method for fast estimation of adsorption isotherm parameters directly from a few overloaded elution profiles and it was recently extended to adsorption isotherm acquisition in gradient elution conditions. However, the inverse method in gradient elution is cumbersome due to the complex adsorption isotherm models found in gradient elution. In this case, physicochemically correct adsorption models have very long calculation times. The aim of this study is to investigate the possibility of using a less complex adsorption isotherm model, with fewer adjustable parameters, but with preserved/acceptable predictive abilities. We found that equal or better agreement between experimental and predicted elution profiles could be achieved with less complex models. By being able to select a model with fewer adjustable parameters, the calculation times can be reduced by at least a factor of 10. 

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