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  • 1.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fundamental Investigations of Supercritical Fluid Chromatography2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis aims at a deeper understanding of Supercritical Fluid

    Chromatography (SFC). Although preparative SFC has started to replace Liquid Chromatography (LC) in the pharmaceutical industry - because of its advantages in speed and its less environmental impact - fundamental understanding is still lacking. Therefore there is no rigid framework to characterize adsorption or to understand the impact of changes in operational conditions.

     

    In Paper I we demonstrated, after careful system verification, that most methods applied to determine adsorption isotherms in LC could not be applied directly in SFC. This was mainly due to operational differences and to the fact that the fluid is compressible which means that everything considered constant in LC varies in SFC.

     

    In Paper II we showed that the most accurate methods for adsorption isotherm determination in LC, the so called plateau methods, do not work properly for SFC. Instead, methods based on overloaded profiles should be preferred.

     

    In Paper III a Design of Experiments approach was successfully used to quantitatively describe the retention behavior of several solutes and the productivity of a two component separation system. This approach can be used to optimize SFC separations or to provide information about the separation system.

     

    In Paper IV severe peak distortion effects, suspected to arise from injection solvent and mobile phase fluid mismatches, were carefully investigated using experiments and simulations. By this approach it was possible to examine the underlying reasons for the distortions, which is vital for method development.

     

    Finally, in Paper V, the acquired knowledge from Paper I-IV was used to perform reliable scale-up in an industrial setting for the first time. This was done by carefully matching the conditions inside the analytical and preparative column with each other. The results could therefore provide the industry with key knowledge for further implementation of SFC.

  • 2.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Asberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. 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
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Evaluation of scale-up from analytical to preparative supercritical fluid chromatography2015In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1425, p. 280-286Article in journal (Refereed)
    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.

  • 3.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Gyllenhaal, Olle
    Computer-assisted optimization in preparative SFC, Challenges, Pitfalls and Solutions2010Conference paper (Refereed)
    Abstract [en]

    Preparative packed column SFC (pSFC) is an environmentally favorable alternative to normal phase HPLC. We are participating in a larger research project where the overreaching goal is to make an impact in the recovery of high-value compounds from agricultural byproducts and waste materials using environmentally sustainable techniques. Our specific task is to isolate large amounts of valuable compounds from discarded biomaterials using pSFC. It is still not possible to accurately model, simulate and optimize a preparative SFC proess, although SFC has been in use for almost fifty years. This is mainly because of the compressibility of the mobile phase and how this influences the physical parameters of the system. More particular, if pSFC is operated under combinations of back pressures and flow rates that give negligible pressure drop, it has been demonstrated and implied, that the tools developed and used within HPLC, can be transferred and used successfully [1, 2]. However, when the pressure drop becomes noticeable, the induced density gradient significantly increases the complexity. An earlier study has clearly described the effect of this pressure gradient on the retention factor, and also the column efficiency [3]. However, it remains to be investigated how the entire adsorption isotherm depends on the density.In this study we will investigate the use of the inverse and the perturbation peak methods, originally developed within LC, to determine the nonlinear adsorption isotherm for i) negligible, and ii) non-negligible pressure drop conditions respectively. To do this, we will use a simple racemic substance and a cellulose based CSP with a column equipped with pressure sensors at the inlet and outlet. Using obtained parameters we will validate the methods by simulating the separation using a variable coefficient version of the Equilibrium-Dispersive model for cases i and ii. [1] S. Ottiger, J. Kluge, A. Rajendran , M. Mazzotti, J. Chromatogr., A 1162 (2007) 74-82[2] C. Wenda, A. Rajendran, J. Chromatogr., A 1216 (2009) 8750-8758[3]A. Rajendran, O. Kräuchi, M. Mazzotti, M. Morbidelli, J Chromatogr., A, 1092 (2005) 149-160[4] G. Guiochon, A. Felinger, D. G. Shirazi, A. M. Katti, Fundamentals of Preparative and Nonlinear Chromatography 2nd Ed, Elsevier Academic Press (2006).

  • 4.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Arnell, Robert
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Kaczmarski, Krzysztof
    A systematic investigation of algorithm impact in preparative chromatography with experimental verifications2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 5, p. 662-672Article in journal (Refereed)
    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

  • 5.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Arnell, Robert
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Kaczmarski, Krzysztof
    Computer Assisted Optimization of Pharmaceutical Purification - The Impact of Algorithms and Experimental Approach2010Conference paper (Refereed)
    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

  • 6.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Kaczmarski, Krzysztof
    A systematic investigation on the accuracy of computer simulations for optical isomers in industrial settings2010Conference paper (Refereed)
    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.

  • 7.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Determination of adsorption isotherms in supercritical fluid chromatography2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1312, p. 124-133Article in journal (Refereed)
    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.

  • 8.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Physics (from 2013).
    Glenne, Emelie
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Leśko, Marek
    Rzeszów University of Technology, Poland.
    Langborg Weinmann, Annika
    AstraZeneca.
    Leek, Tomas
    AstraZeneca.
    Kaczmarski, Krzysztof
    AstraZeneca.
    Klarqvist, Magnus
    AstraZeneca.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Investigation of robustness for supercritical fluid chromatography separation of peptides: Isocratic vs gradient mode2018In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, p. 177-187Article in journal (Refereed)
    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.

  • 9.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013). Uppsala University.
    Rova, Maria
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Örnskov, Eivor
    IMED Biotech Unit, Sweden.
    Schweikart, Fritz
    IMED Biotech Unit, Sweden.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Investigation of factors influencing the separation of diastereomers of phosphorothioated oligonucleotides2019In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, no 15, p. 3383-3394Article in journal (Refereed)
    Abstract [en]

    This study presents a systematic investigation of factors influencing the chromatographic separation of diastereomers of phosphorothioated pentameric oligonucleotides as model solutes. Separation was carried out under ion-pairing conditions using an XBridge C18 column. For oligonucleotides with a single sulfur substitution, the diastereomer selectivity was found to increase with decreasing carbon chain length of the tertiary alkylamine used as an ion-pair reagent. Using an ion-pair reagent with high selectivity for diastereomers, triethylammonium, it was found the selectivity increased with decreased ion-pair concentration and shallower gradient slope. Selectivity was also demonstrated to be dependent on the position of the modified linkage. Substitutions at the center of the pentamer resulted in higher diastereomer selectivity compared to substitutions at either end. For mono-substituted oligonucleotides, the retention order and stereo configuration were consistently found to be correlated, with Rp followed by Sp, regardless of which linkage was modified. The type of nucleobase greatly affects the observed selectivity. A pentamer of cytosine has about twice the diastereomer selectivity of that of thymine. When investigating the retention of various oligonucleotides eluted using tributylammonium as the ion-pairing reagent, no diastereomer selectivity could be observed. However, retention was found to be dependent on both the degree and position of sulfur substitution as well as on the nucleobase. When analyzing fractions collected in the front and tail of overloaded injections, a significant difference was found in the ratio between Rp and Sp diastereomers, indicating that the peak broadening observed when using tributylammonium could be explained by partial diastereomer separation.

  • 10.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    A Deeper Understanding of a Complex Adsorption Behavior in a Common Chiral, Separation System2011Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    A thermodynamic and kinetic study of an unusual adsorption behavior-Methyl Mandelate on commercially available Tris-(3,5- dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase2012Conference paper (Other academic)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Characterization of the Adsorption of Racemic Methyl Mandelate on Tris-(3,5-dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase2011Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    On the Reproducibility between Different Modern Supercritcal Fluid Chromatographic Systems2013Conference paper (Other academic)
    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.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Using Modern SFC Systems for Adsorption Characterization2013Conference paper (Other academic)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Preparative Separation of Chiral Pharmaceutical Compounds - The Effects of Packing Particle Size, Pressure Limit and Column Geometry on Productivity and Solvent Consumption2011Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Preparative Separation of Omeprazole: Predictions of the Optimal Experimental Conditions by Computer Simulations2011Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    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 Phase2011Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Forss, Erik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography2014In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1354, p. 129-138Article in journal (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enantioseparation of omeprazole effect of different packing particle size on productivity2012In: Journal of Chromatography A, ISSN 0021-9673, Vol. 1240, no 1, p. 123-131Article in journal (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Högblom, Joakim
    Eka Chemicals.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Adsorption Isotherm Determination for Reliable Phase System Characterization in SFC: Challenges and Pitfalls2012Conference paper (Refereed)
    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.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Undin, Torgny
    Uppsala University Analytisk Kemi.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Characterization of an unusual adsorption behavior of racemic methyl-mandelate on a tris-(3,5-dimethylphenyl) carbamoyl cellulose chiral stationary phase2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 38, p. 6688-6696Article in journal (Refereed)
    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.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    The Effect of Temperature, Pressure and Co-Solvent on a Chiral Supercritical Fluid Chromatography Separation2014In: Chromatography Today, ISSN 1752-8070, Vol. 7, no 3, p. 14-17Article in journal (Refereed)
  • 23.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Shalliker, Andrew
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    A closer study of peak distortions in supercritical fluid chromatography as generated by the injection2015In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1400, p. 131-139Article in journal (Refereed)
    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.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Lesko, Marek
    Rzeszow University of Technology.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Physics.
    Forssén, Patrik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Kaczmarski, Krzysztof
    Rzeszow University of Technology.
    New Procedure for Predictions of Overloaded Profiles in Gradient Elution2013Conference paper (Other academic)
    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

  • 25.
    Forss, Erik
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013). Karlstad Univ, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
    Haupt, Dan
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Stalberg, Olle
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Chemometric evaluation of the combined effect of temperature, pressure, and co-solvent fractions on the chiral separation of basic pharmaceuticals using actual vs set operational conditions2017In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1499, p. 165-173Article in journal (Refereed)
    Abstract [en]

    The need to determine the actual operational conditions, instead of merely using the set operational conditions, was investigated for in packed supercritical fluid chromatography (SFC) by design of experiments (DoE) using a most important type of compounds, pharmaceutical basics, as models. The actual values of temperature, pressure, and methanol levels were recorded and calculated from external sensors, while the responses in the DoE were the retention factors and selectivity. A Kromasil CelluCoat columh was used as the stationary phase, carbon dioxide containing varying methanol contents as the mobile phase, and the six racemates of alprenolol, atenolol, metoprolol, propranolol, clenbuterol, and mianserin were selected as model solutes. For the retention modeling, the most important term was the methanol fraction followed by the temperature and pressure. Significant differences (p<0.05) between most of the coefficients in the retention models were observed when comparing models from set and actual conditions. The selectivity was much less affected by operational changes, and therefore was not severely affected by difference between set and actual conditions. The temperature differences were usually small, maximum +/- 1.4 degrees C, whereas the pressure differences were larger, typically approximately +10.5 bar. The set and actual fractions of methanol also differed, usually by +/- 0.4 percentage points. A cautious conclusion is that the primary reason for the discrepancy between the models is a mismatch between the set and actual methanol fractions. This mismatch is more serious in retention models at low methanol fractions. The study demonstrates that the actual conditions should almost always be preferred. (C) 2017 Elsevier B.V. All rights reserved.

  • 26.
    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
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    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
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Evaluation and analysis of environmentally sustainable methodologies for extraction of betulin from birch bark with a focus on industrial feasibility2016In: Green Chemistry, ISSN 1463-9262, E-ISSN 1463-9270, Vol. 18, no 2, p. 516-523Article in journal (Refereed)
    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%.

  • 27.
    Lesko, Marek
    et al.
    Rzeszów University of Technology, Poland.
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Poland.
    Choice of Model for Estimation of Adsorption Isotherm Parameters in Gradient Elution Preparative Liquid Chromatography2015In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 78, no 19-20, p. 1293-1297Article in journal (Refereed)
    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. 

  • 28.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Highlighting Important Parameters Often Neglected in Numerical Optimization of Preparative Chromatography2012In: Chemical Engineering & Technology, ISSN 0930-7516, E-ISSN 1521-4125, Vol. 35, no 1, p. 149-156Article in journal (Refereed)
    Abstract [en]

    When a chromatographic separation process is numerically optimized, a number of input parameters to the column model need to be accurately determined, and the accuracy will affect the reliability of the predicted optimal operational conditions. Furthermore, the numerical accuracy of the solution to the column model will have similar impact. The input parameters holdup volume, injection profiles, and the selection of an algorithm for solving the column model were investigated. Errors in parameters or a numerical error in the solution of the column model were found to lead to a prediction of a product fraction where the set purity and/or yield requirements are not met.

  • 29.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Högblom, Joakim
    Eka Chemicals.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Characterization of adsorption in SFC: An evaluation of methods used in LC2012Conference paper (Refereed)
    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

  • 30.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Leśko, Marek
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Högblom, Joakim
    Karlsson, Anders
    Kaczmarski, Krzysztof
    Optimizing Column Length and Particle Size in Preparative Batch Chromatography Using Enantiomeric Separations of Omeprazole and Etiracetam as Models: Feasibility of Taguchi Empirical Optimization2018In: Chromatographia, Vol. 81, no 6, p. 851-860Article in journal (Refereed)
    Abstract [en]

    The overreaching purpose of this study is to evaluate new approaches for determining the optimal operational and column conditions in chromatography laboratories, i.e., how best to select a packing material of proper particle size and how to determine the proper length of the column bed after selecting particle size. As model compounds, we chose two chiral drugs for preparative separation: omeprazole and etiracetam. In each case, two maximum allowed pressure drops were assumed: 80 and 200 bar. The processes were numerically optimized (mechanistic modeling) with a general rate model using a global optimization method. The numerical predictions were experimentally verified at both analytical and pilot scales. The lower allowed pressure drop represents the use of standard equipment, while the higher allowed drop represents more modern equipment. For both compounds, maximum productivity was achieved using short columns packed with small-particle size packing materials. Increasing the allowed backpressure in the separation leads to an increased productivity and reduced solvent consumption. As advanced numerical calculations might not be available in the laboratory, we also investigated a statistically based approach, i.e., the Taguchi method (empirical modeling), for finding the optimal decision variables and compared it with advanced mechanistic modeling. The Taguchi method predicted that shorter columns packed with smaller particles would be preferred over longer columns packed with larger particles. We conclude that the simpler optimization tool, i.e., the Taguchi method, can be used to obtain “good enough” preparative separations, though for accurate processes, optimization, and to determine optimal operational conditions, classical numerical optimization is still necessary

  • 31.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Ņsberg, Dennis
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Modeling Competitive Adsorption Isotherms in Gradient Elution Nonlinear Reversed Phase Liquid Chromatography.2012Conference paper (Refereed)
    Abstract [en]

    Several important studies – based on firm theory ground - have been made on the different parameters of importance in chromatographic process optimizations during the recent years. In this presentation we take an holistic view by investigating i) the relative importance of the operational parameters and column properties and ii) how these effect the optimal column design. For optimization we used an advanced global response surface method combined with local gradient methods. As a model system we used the practical problem of purification of one or both optical isomers of a racemate. In the first part, we investigated the relative importance of stationary phase characteristics such as: (i) the retention factor, (ii) the selectivity, (iii) the saturation capacity (iv), the efficiency and (v) the maximum allowed operational pressure. In the second part we investigated how the optimal column design for a preparative separation problem is affected by column properties, such as particle size, and optimization constraints, such as required yield. The investigation showed – in contrast to what is generally believed – that the saturation capacity of the stationary phase is of minor importance, instead the maximum allowed operational pressure is one of the most important parameter. Moreover, smaller size packing materials always shows much lower solvent consumption. This is a great environmental and economical advantage of using smaller packing materials. Rules of thumbs, derived from the holistic optimizations, will be given for industrial preparative settings in the batch mode.

  • 32.
    Vera, C. M.
    et al.
    Phenomenex Australia Pty Ltd, Lane Cove, NSW 2067, Australia..
    Shock, D.
    Phenomenex Australia Pty Ltd, Lane Cove, NSW 2067, Australia..
    Dennis, G. R.
    Univ Western Sydney, Sch Sci & Hlth, Australian Ctr Res Separat Sci, Penrith, NSW 2751, Australia..
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Shalliker, R. A.
    Univ Western Sydney, Sch Sci & Hlth, Australian Ctr Res Separat Sci, Penrith, NSW 2751, Australia.
    Contrasting selectivity between HPLC and SFC using phenyl-type stationary phases: A study on linear polynuclear aromatic hydrocarbons2015In: Microchemical journal (Print), ISSN 0026-265X, E-ISSN 1095-9149, Vol. 119, p. 40-43Article in journal (Refereed)
    Abstract [en]

    A selectivity study was undertaken using two types of phenyl-type (Synergi polar RP and Cosmosil 5PBB) stationary phases in supercritical fluid chromatography. The mobile phases used in the SFC environment employed CO2 with methanol as the modifier. These columns were tested using linear polynuclear aromatic hydrocarbons as the test solutes. The retention behaviour of these PAHs in SFC was compared to their behaviour in HPLC and there were very distinct differences. On the Synergi-polar stationary phase the PAH selectivity was highly dependent on the methanol modifier concentration, but in comparison on the Cosmosil column, the selectivity between the members of this PAH test group showed almost no change as a function of the methanol concentration, even though the retentivity on the Cosmosil stationary phase was far greater than the Synergi stationary. In fact, the mobile phase played a very passive role in the separations observed on the Cosmosil stationary phase. (C) 2014 Elsevier B.V. All rights reserved.

  • 33.
    Vera, C. M.
    et al.
    Phenomenex Australia, Pty Ltd, Lane Cove, NSW 2067, Australia.
    Shock, D.
    Phenomenex Australia, Pty Ltd, Lane Cove, NSW 2067, Australia.
    Dennis, G. R.
    Australian Centre for Research on Separation Science, School of Science and Health, University of Western Sydney, Penrith, NSW 2751, Australia.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Shalliker, R. Andrew
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Australian Centre for Research on Separation Science, School of Science and Health, University of Western Sydney, Penrith, NSW 2751, Australia.
    A preliminary study on the selectivity of linear polynuclear aromatic hydrocarbons in SFC using phenyl-type stationary phases2015In: Microchemical journal (Print), ISSN 0026-265X, E-ISSN 1095-9149, Vol. 121, p. 136-140Article in journal (Refereed)
    Abstract [en]

    The retention behaviour of a homologous series of polyaromatic hydrocarbons was evaluated on two phenyl-type stationary phases in reversed phase supercritical fluid chromatography (SFC). These phases were the Synergi polar-RP phase and the Cosmosil 5PBB phase, both of which are polar end-capped and incorporate an ether in a propyl chain that tethers the phenyl ring to the silica surface. The Cosmosil 5PBB phase also has five bromine atoms on the phenyl ring. The retention capacity of the Cosmosil column was substantially greater than the Synergi column. However, selectivity on the Cosmosil column was effectively independent of the acetonitrile modifier composition in the CO2 mobile phase, whereas, selectivity on the Synergi column was greatly affected by the acetonitrile modifier in the CO2 mobile phase. The results from this study showed that selectivity and retention studies in HPLC cannot be used to predict selectivity and retention behaviour in SFC. (C) 2015 Elsevier B.V. All rights reserved.

  • 34.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    An Experimental and Theoretical investigation on Mobile PhaseEffects on Competitive Adsorption Isotherms in Preparative LC2012Conference paper (Refereed)
    Abstract [en]

    This poster serves as background information to the corresponding lecture. Mobile phase gradients have been used in LC since the 1950s and are still an important programming technique in both analytical and preparative LC. Improving the resolution, and thereby making the separation of complex samples possible, and reducing the separation time, which increases the productivity, are the two main advantages of gradient elution. The modelling of band profiles and the optimization of preparative separations has largely been studied under isocratic conditions. The shape of the gradient and the behaviour of the solutes are often determined experimentally with scarce knowledge about the underlying physicochemical equations. This "trial and error" approach results in time consuming and, possibly, expensive experiments. The goal of this work is to investigate the dependence of the adsorption behaviour on the mobile phase composition in reversed phase LC. By knowing the adsorption isotherm as a function of the concentrations of both the solute and the strong organic modifier, the band profiles are modelled under gradient elution conditions.Our aim is to make it possible to use modelling tools so one can optimize a separation and especially the gradient shape. Recent studies have shown that a significant improvement in productivity can be achieved if the gradient shapes are designed carefully [1,2].In this study we discuss how to obtain the adsorption isotherm data experimentally for two substances using the perturbation peak method. The substances which are investigated are cyclohexanone and cycloheptanone on a Kromasil C18-column with methanol-water as the mobile phase. The fitting of the nonlinear experimental data to appropriate theoretical isotherm models will also be discussed.For practical reasons, we will also be looking at how different key parameters, e.g. the column hold-up time, the column efficiency, the retention factor and the equilibrium constant, change with the mobile phase composition.With the experimentally determined adsorption isotherm as a basis, we will simulate overloaded band profiles under gradient elution conditions and compare the simulated results with experimentally obtained band profiles.A contribution from the Fundamental Separation Science Group www.separationscience.se

  • 35.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Evaluation of co-solvent fraction, pressure and temperature effects in analytical and preparative supercritical fluid chromatography2014In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1374, p. 254-260Article in journal (Refereed)
    Abstract [en]

    Abstract A chemometric approach is used for studying the combined effect of temperature, pressure and co-solvent fraction in analytical and preparative supercritical fluid chromatography (SFC). More specifically, by utilizing design of experiments coupled with careful measurements of the experimental conditions the interaction between pressure, temperature and co-solvent fraction was studied with respect to productivity, selectivity and retention in chiral SFC. A tris-(3,5-dimethylphenyl) carbamoyl cellulose stationary phase with carbon dioxide/methanol as mobile phase and the two racemic analytes trans-stilbene oxide (TSO) and 1,1′-bi-2-naphthol (BINOL) were investigated. It was found for the investigated model system that the co-solvent fraction and pressure were the parameters that most affected the retention factors and that the co-solvent fraction and column temperature were most important for controlling the selectivity. The productivity in the preparative mode of SFC was most influenced by the co-solvent fraction and temperature. Both high co-solvent fraction and temperature gave maximum productivity in the studied design space.

  • 36.
    Ņsberg, Dennis
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Enmark, Martin
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Modelling of Overloaded Gradient Elution in Reversed-Phase Liquid Chromatography2012Conference paper (Refereed)
    Abstract [en]

    Mobile phase gradients have been used in LC since the 1950s and are still an important programming technique in both analytical and preparative LC. Improving the resolution, and thereby making the separation of complex samples possible - and thus reducing the separation time which increases the productivity- are the two main advantages of gradient elution. The modelling of band profiles and the optimization of preparative separations has largely been studied under isocratic conditions. The shape of the gradient and the behaviour of the solutes are often determined experimentally with scarce knowledge about the underlying physicochemical equations. This “trial and error” approach results in time consuming and, possibly, expensive experiments. The goal of this work is to investigate the dependence of the adsorption behaviour on the mobile phase composition in reversed phase LC. By knowing the adsorption isotherm as a function of the concentrations of both the solute and the strong organic modifier, the band profiles can be modelled under gradient elution conditions. Our aim is to make it possible to use modelling tools for a more reliable computer-assisted optimization, accounting for the gradient shape. Recent studies have shown that a significant improvement in productivity can be achieved if the gradient shapes are designed carefully [1,2]. In this presentation we will discuss how to obtain the adsorption isotherm data experimentally for two substances using the perturbation peak method. The substances investigated are cyclohexanone and cycloheptanone on a system comprising of a Kromasil C18-column and methanol-water as mobile phase. The fitting of the nonlinear experimental data to appropriate theoretical isotherm models will also be discussed. For practical reasons, we will also be looking at how different key parameters, e.g. the column hold-up time, the column efficiency, the retention factor and the equilibrium constant, change with the mobile phase composition. With the experimentally determined adsorption isotherm as a basis, we will simulate overloaded band profiles under gradient elution conditions and compare the simulated results with experimentally obtained band profiles. A contribution from the Fundamental Separation Science Group www.separationscience.se

  • 37.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Lesko, Marek
    Rzeszow University of Technology.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Forssén, Patrik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Kaczmarski, Krzysztof
    Rzeszow University of Technology.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Prediction of Overloaded Profiles in Gradient Elution Chromatography2013Conference paper (Other academic)
    Abstract [en]

    This poster is a compliment to the oral presentation “A new procedure for improved predictions of overloaded profiles in gradient elution”. In order 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 that covers 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. We 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 the calculated and the experimental elution profiles. This is an extension of the inverse 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 makes it possible 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. A similar situation occurs in SFC and the proposed approach could with modifications probably be used also there. This is a contribution from the Fundamental Separation Science Group www.FSSG.se

  • 38.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Leśko, Marek
    Department of Chemical Engineering, Rzeszów University of Technology, Rzeszów, Poland.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Kaczmarski, Krzysztof
    Department of Chemical Engineering, Rzeszów University of Technology, Rzeszów, Poland.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fast estimation of adsorption isotherm parameters in gradient elution preparative liquid chromatography. I: The single component case2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1299, p. 64-70Article in journal (Refereed)
    Abstract [en]

    The inverse method is a numeric method for fast estimation of adsorption isotherm parameters directly from overloaded elution profiles. However, it has previously only been used for isocratic experiments. Here we will extend the inverse method so it can be used for gradient elution too. This extended inverse method will make it possible 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. Our extended inverse method was verified using both simulations and real experiments. For simulated overloaded elution profiles we were able to determine almost exact Langmuir adsorption isotherm parameters with the new approach. From real experimental data, bi-Langmuir adsorption parameters were estimated using both the perturbation peak method and the extended inverse method. The shape of the acquired adsorption isotherms did match over the considered concentration range; however, the adsorption isotherm parameters found with the two methods were not the same. This is probably due to the fact that adsorption isotherm estimated with the inverse method is only a good approximation up to the highest eluted concentration in the used chromatograms. But this is not a serious drawback from a process point of view where the main objective is to make accurate predictions of elution profiles. The bi-Langmuir adsorption isotherm obtained with both methods could accurately predict the shape of overloaded elution profiles.

  • 39.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Leśko, Marek
    Department of Chemical and Process Engineering, Rzeszów University of Technology.
    Enmark, Martin
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Kaczmarski, Krzysztof
    Department of Chemical and Process Engineering, Rzeszów University of Technology.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Fast estimation of adsorption isotherm parameters in gradient elution preparative liquid chromatography. II: The competitive case2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1314, no Nov, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Abstract Experimental competitive adsorption isotherms were successfully determined directly from overloaded elution profiles in gradient elution mode using an extended inverse method. This approach differs from the existing methods in one important aspect – no isocratic experiments are necessary which makes it possible to study adsorption of substances whose retention factors vary strongly with the mobile-phase composition. The approach was verified with simulated binary data and with experimental data from gradient separations of a cyclohexanone/cycloheptanone mixture. For the synthetic data, the original adsorption isotherm parameters were found using a two-step estimation procedure. In the first step analytical peaks were used to estimate the “analytical” part of the Langmuir equation and in the second step the association equilibrium parameters were estimated from two simulated overloaded elution profiles. For the experimental data, a three-step approach was used. The two first steps were used to reduce the calculation time so that parameter estimation could be performed on an ordinary computer. In the first step, analytical peaks were used to estimate the “analytical” part of the bi-Langmuir equation. In the second step, initial guesses for all other parameters were determined separately for each solute using the faster Rouchon algorithm. In the final and third step, the more accurate orthogonal collocation on finite elements algorithm, was used to fine-tune the isotherm parameters. The model could accurately predict the shape of overloaded elution profiles. The shape of the adsorption isotherms agreed well with those determined with the standard isocratic method, although the numerical values were not the same. The extended inverse method is well suited for process optimization where few experiments and accurate predictions are important.

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