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  • 1.
    Bagge, Joakim
    et al.
    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).
    Lesko, Marek
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Lime, Fredrik
    Nouryon.
    Fornstedt, Torgny
    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).
    Impact of stationary-phase pore size on chromatographic performance using oligonucleotide separation as a model2020In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1634, p. 1-10, article id 461653Article in journal (Refereed)
    Abstract [en]

    A combined experimental and theoretical study was performed to understand how the pore size of packing materials with pores 60-300 angstrom in size affects the separation of 5-50-mer oligonucleotides. For this purpose, we developed a model in which the solutes were described as thin rods to estimate the accessible surface area of the solute as a function of the pore size and solute size. First, an analytical investigation was conducted in which we found that the selectivity increased by a factor of 2.5 when separating 5- and 15-mer oligonucleotides using packing with 300 angstrom rather than 100 angstrom pores. We complemented the analytical investigation by theoretically demonstrating how the selectivity is dependent on the column's accessible surface area as a function of solute size. In the preparative investigation, we determined adsorption isotherms for oligonucleotides using the inverse method for separations of a 9- and a 10-mer. We found that preparative columns with a 60 angstrom-pore-size packing material provided a 10% increase in productivity as compared with a 300 A packing material, although the surface area of the 60 angstrom packing is as much as five time larger.

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  • 2.
    Blomberg, Lars G
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Abdel-Rehim, M
    Recent advances in microextraction by packed sorbent for bioanalysis2010In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, no 16, p. 2569-2580Article in journal (Refereed)
  • 3.
    Bohlin, Maria E.
    et al.
    Karlstad University, Division for Chemistry.
    Kogutowska, Ewa
    Department of Autoimmunology, Statens Serum Institut, Copenhagen.
    Blomberg, Lars G.
    Karlstad University, Division for Chemistry.
    Heegaard, Niels H.H.
    Department of Autoimmunology, Statens Serum Institut, Copenhagen.
    Capillary electrophoresis-based analysis of phospholipid and glycosaminoglycan binding by human β2-glycoprotein I2004In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1059, p. 215-222Article in journal (Refereed)
  • 4.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Asberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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 (from 2013).
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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.

  • 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
    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

  • 6.
    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.

  • 7.
    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.

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  • 8.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Physics (from 2013).
    Harun, Said
    AstraZeneca.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013). Centre for Clinical Research.
    Ornskov, Eivor
    AstraZeneca.
    Thunberg, Linda
    AstraZeneca.
    Dahlen, Anders
    AstraZeneca.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Selectivity limits of and opportunities for ion pair chromatographic separation of oligonucleotides2021In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1651, article id 462269Article in journal (Refereed)
    Abstract [en]

    A B S T R A C T Here it was investigated how oligonucleotide retention and selectivity factors are affected by electrostatic and non-electrostatic interactions in ion pair chromatography. A framework was derived describing how selectivity depends on the electrostatic potential generated by the ion-pair reagent concentration, co-solvent volume fraction, charge difference between the analytes, and temperature. Isocratic experiments verified that, in separation problems concerning oligonucleotides of different charges, selectivity increases with increasing surface potential and analyte charge difference and with decreasing co-solvent volume fraction and temperature. For analytes of the same charge, for example, diastereomers of phosphorothioated oligonucleotides, selectivity can be increased by decreasing the co-solvent volume fraction or the temperature and has only a minor dependency on the ion-pairing reagent concentration. An important observation is that oligonucleotide retention is driven predominantly by electrostatic interaction generated by the adsorption of the ion-pairing reagent. We therefore compared classical gradient elution in which the co-solvent volume fraction increases over time versus gradient elution with a constant co-solvent volume fraction but with decreasing ion-pair reagent concentration over time. Both modes decrease the electrostatic potential. Oligonucleotide selectivity was found to increase with decreasing ion pairing reagent concentration. The two elution modes were finally applied to two different model anti sense oligonucleotide separation problems, and it was shown that the ion-pair reagent gradient increases the selectivity of non-charge & ndash;based separation problems while maintaining charge-difference & ndash;based selectivity. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

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  • 9.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Häggstrom, Jakob
    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).
    Building machine-learning-based models for retention time and resolution predictions in ion pair chromatography of oligonucleotides2022In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1671, article id 462999Article in journal (Refereed)
    Abstract [en]

    Support vector regression models are created and used to predict the retention times of oligonucleotides separated using gradient ion-pair chromatography with high accuracy. The experimental dataset consisted of fully phosphorothioated oligonucleotides. Two models were trained and validated using two pseudo orthogonal gradient modes and three gradient slopes. The results show that the spread in retention time differs between the two gradient modes, which indicated varying degree of sequence dependent separation. Peak widths from the experimental dataset were calculated and correlated with the guanine cytosine content and retention time of the sequence for each gradient slope. This data was used to predict the resolution of the n - 1 impurity among 250 0 0 0 random 12-and 16-mer sequences; showing one of the investigated gradient modes has a much higher probability of exceeding a resolution of 1.5, particularly for the 16-mer sequences. Sequences having a high guanine-cytosine content and a terminal C are more likely to not reach critical resolution. The trained SVR models can both be used to identify characteristics of different separation methods and to assist in the choice of method conditions, i.e. to optimize resolution for arbitrary sequences. The methodology presented in this study can be expected to be applicable to predict retention times of other oligonucleotide synthesis and degradation impurities if provided enough training data.

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  • 10.
    Enmark, Martin
    et al.
    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).
    Development of a unified gradient theory for ion-pair chromatography using oligonucleotide separations as a model case2023In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1691, article id 463823Article in journal (Refereed)
    Abstract [en]

    Ion-pair chromatography is the de facto standard for separating oligonucleotides and related impurities, particularly for analysis but also often for small-scale purification. Currently, there is limited understanding of the quantitative modeling of both analytical and overloaded elution profiles obtained during gradient elution in ion-pair chromatography. Here we will investigate a recently introduced gradient mode, the so-called ion-pairing reagent gradient mode, for both analytical and overloaded separations of oligonucleotides. The first part of the study demonstrates how the electrostatic theory of ion-pair chromatography can be applied for modeling gradient elution of oligonucleotides. When the ion-pair gradient mode is used in a region where the electrostatic surface potential can be linearized, a closed-form expression of retention time can be derived. A unified retention model was then derived, applicable for both ion-pair reagent gradient mode as well as co-solvent gradient mode. The model was verified for two different experimental systems and homo- and heteromeric oligonucleotides of different lengths. Quantitative modeling of overloaded chromatography using the ion-pairing reagent gradient mode was also investigated. Firstly, a unified adsorption isotherm model was developed for both gradient modes. Then, adsorption isotherms parameter of a model oligonucleotide and two major synthetic impurities were estimated using the inverse method. Secondly, the parameters of the adsorption isotherm were then used to investigate how the productivity of oligonucleotide varies with injection volume, gradient slope, and initial retention factor. Here, the productivity increased when using a shallow gradient slope combined with a low initial retention factor. Finally, experiments were conducted to confirming some of the model predictions. Comparison with the conventional co-solvent gradient mode showed that the ion-pairing reagent gradient leads to both higher yield and productivity while consuming less co-solvent.

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  • 11.
    Enmark, Martin
    et al.
    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).
    Forss, Erik
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Forssén, Patrik
    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 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.

  • 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.
    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.

  • 13.
    Enmark, Martin
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Shalliker, Andrew
    Australian Centre for Research on Separation Science, School of Science and Health, University of Western Sydney, Parramatta, NSW, Australia.
    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).
    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.

  • 14.
    Eriksson, Björn
    et al.
    Karlstad University, Division for Chemistry.
    Andersson, Magnus
    Department of Analytical Chemistry, Pharmaceutical and Analytical Research and Development, AstraZeneca AB, Sweden.
    Blomberg, Lars
    Karlstad University, Division for Chemistry.
    Deviation from Ohm’s law in electric field assisted capillary LC2003In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1010, no 1, p. 17-24Article in journal (Refereed)
  • 15.
    Eriksson, Björn
    et al.
    Karlstad University, Faculty of Technology and Science.
    Andersson, Magnus
    Analytical Development, Pharmaceutical and Analytical Research and Development, AstraZeneca, Sweden.
    Blomberg, Lars
    Karlstad University, Faculty of Technology and Science.
    Flow splitting at the inlet electrode as a method for decreasing the electric current in electric field assisted liquid chromatography2006In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1119, no 1-2, p. 170-175Article in journal (Refereed)
  • 16.
    Eriksson, Björn
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Skuland, Inger Lill
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Marlin, Nicola
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Andersson, Magnus
    Early Development, Pharmaceutical and Analytical Research & Development, AstraZeneca, Sweden.
    Blomberg, Lars
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    In-line application of electric field in capillary separation systems Part I: Joule heating, pH and conductivity2008In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 75, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    This study concerns the technique electric field-assisted capillary liquid chromatography. In this technique, an electric field is applied over the separation capillary in order to provide an additional selectivity. In this technique, the electric field is applied in-line in the separation capillary and here the electric current is the factor limiting the magnitude of applied electric field. The influence of Joule heating and other factors on the current in such systems has been investigated.

    The temperature in the capillary was first measured within a standard CE set-up, as function of effect per unit of length. Then the same cooling system was applied to an in-line set-up, to replicate the conditions between the two systems, and thus the temperature. Thus Joule heating effects could then be calculated within the in-line system. It was found that for systems applying an electric field in line, the direct influence from Joule heating was only relatively small.

    The pH in the capillary was measured in the in-line set-up using cresol red/TRIS solutions as pH probe. Significant changes in pH were observed and the results suggested that electrolysis of water is the dominant electrode reaction in the in-line system. In summary, the observed conductivity change in in-line systems was found to be mainly due to the pH change by hydrolysis of water, but primarily not due the temperature change in the capillary column.

  • 17.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Introduction to "Fundamental challenges and opportunities for preparative supercritical fluid chromatography by G. Guiochon, A. Tarafder [J. Chromatogr. A 1218 (2011) 1037-1114]"2016In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1446, p. 19-20Article in journal (Other academic)
  • 18.
    Fornstedt, Torgny
    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.
    Edström, Lena
    Deformations of overloaded bands under pH-stable conditions in reversed phase chromatography2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 15, p. 1966-1973Article in journal (Refereed)
    Abstract

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

  • 19.
    Fornstedt, Torgny
    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.
    Edström, Lena
    Department of Physical and Analytical Chemistry, Uppsala University.
    Forssén, Patrik
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Injection profiles in liquid chromatography. I. A fundamental investigation2010In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, no 26, p. 4306-4312Article in journal (Refereed)
    Abstract [en]

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

  • 20.
    Forss, Erik
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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.

  • 21.
    Forssen, Patrik
    et al.
    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 model free method for estimation of complicated adsorption isotherms in liquid chromatography2015In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1409, p. 108-115Article in journal (Refereed)
    Abstract [en]

    Here we show that even extremely small variations in the adsorption isotherm can have a tremendous effect on the shape of the overloaded elution profiles and that the earlier in the adsorption isotherms the variation take place, the larger its impact on the shape of the elution profile. These variations are so small that they can be "hidden" by the discretization and in the general experimental noise when using traditional experimental methods, such as frontal analysis, to measure adsorption isotherms. But as the effects of these variations are more clearly visible in the elution profiles, the Inverse Method (IM) of adsorption isotherm estimation is an option. However, IM usually requires that one selects an adsorption isotherm model prior to the estimation process. Here we show that even complicated models might not be able to estimate the adsorption isotherms with multiple inflection points that small variations might give rise to. We therefore developed a modified IM that, instead of fixed adsorption isotherm models, uses monotone piecewise interpolation. We first validated the method with synthetic data and showed that it can be used to estimate an adsorption isotherm, which accurately predicts an extremely "strange" elution profile. For this case it was impossible to estimate the adsorption isotherm using IM with a fixed adsorption model. Finally, we will give an example of a real chromatographic system where adsorption isotherm with inflection points is estimated by the modified IM.

  • 22.
    Forssén, Patrik
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Edström, Lena
    Uppsala University.
    Lämmerhofer, Michael
    Institute of Pharmaceutical Sciences, University of Tübingen, Germany.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Karlsson, Anders
    Department of Molecular Biology, Göteborg University .
    Lindner, Wolfgang
    Department of Analytical Chemistry, University of Vienna, Austria.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences. Uppsalas universitet.
    Optimization strategies accounting for the additive in preparative chiral liquid chromatography2012In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1269, p. 279-286, article id SIArticle in journal (Refereed)
    Abstract [en]

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

  • 23.
    Forssén, Patrik
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Edström, Lena
    Uppsala University.
    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.
    Injection profiles in liquid chromatography II: Predicting accurate injection-profiles for computer-assisted preparative optimizations2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 34, p. 5794-5800Article in journal (Refereed)
    Abstract [en]

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

  • 24.
    Forssén, Patrik
    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.
    Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography. I: Investigation of a chiral separation system2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1299, p. 58-63Article in journal (Refereed)
    Abstract [en]

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

  • 25.
    Forssén, Patrik
    et al.
    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).
    Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography II: Investigation of separation systems with competitive Langmuir adsorption isotherms2014In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1347, p. 72-79Article in journal (Refereed)
    Abstract [en]

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

  • 26.
    Glenne, Emelie
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Leek, Hanna
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, 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).
    Peak deformations in preparative supercritical fluid chromatography due to co-solvent adsorption2016In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1468, p. 200-208Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Glenne, Emelie
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Leek, Hanna
    AstraZeneca R&D, Innovat Med & Early Dev, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med & Early Dev, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, Jörgen
    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).
    Systematic investigations of peak deformations due to co-solvent adsorption in preparative supercritical fluid chromatography2017In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1496, p. 141-149Article in journal (Refereed)
    Abstract [en]

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

  • 28.
    Glenne, Emelie
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Ohlen, Kristina
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Leek, Hanna
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Klarqvist, Magnus
    AstraZeneca R&D, Innovat Med, Resp Inflammat & Autoimmun, S-43183 Molndal, Sweden..
    Samuelsson, Jorgen
    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).
    A closer study of methanol adsorption and its impact on solute retentions in supercritical fluid chromatography2016In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1442, p. 129-139Article in journal (Refereed)
    Abstract [en]

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

  • 29.
    Haseeb, Abdul
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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).
    Method development for the acquisition of adsorption isotherm of ion pair reagents Tributylamine and Triethylamine in ion pair chromatography2023In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1687, article id 463687Article in journal (Refereed)
    Abstract [en]

    Tributylamine (TBuA) and triethylamine (TEtA) are the most commonly used ion pair reagents in ion pair chromatography especially for the analysis of oligonucleotides. In order to improve the understanding of the retention and separation mechanism of oligonucleotides in ion pair chromatography, it is important to understand the retention mechanism and the nature of interaction of these ion pair reagents with the stationary phase in the chromatographic column. Adsorption isotherm is helpful in evaluating such interactions, and subsequently predicting the retention mechanism. Alkylamines are very polar molecules which lack suitable chromophore and are commonly present in charged forms. Therefore, their determination and the subsequent acquisition of their adsorption isotherms using traditional liquid chromatography is very difficult. In this study, we first developed an analytical method for the determination of TBuA and TEtA in a typical chromatographic mobile phase (acetonitrile-water) and then used the same method to acquire the adsorption isotherms for tributylammonium acetate (TBuAA) and triethylammonium acetate (TEtAA). This method started with the conversion of the alkylammonium ions to free neutral forms by treating the sample with a strong base, followed by pentane-mediated extraction and finally the analysis of the extracts using gas chromatography-flame ionization detector (GC-FID). This three-step method was validated for parameters like range, linearity, intra-day and inter-day precision and accuracy, limit of detection and limit of quantitation. For the adsorption isotherms, the C18 column was first equilibrated with the solutions having different concentrations of alkylammonium ions and then stripped with eluent devoid of alkylammonium ions. Several stripping eluents were investigated and it was discovered that the eluent requirement could be decreased by the addition of sodium chloride. The effluents from the stripping phase were collected and analyzed using the developed analytical method to acquire the adsorption data. Under the investigated conditions, adsorption of TBuAA and TEtAA showed type III and type I isotherm behavior respectively. 

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  • 30.
    Hernandez, Victor Agmo
    et al.
    Uppsala University, Sweden.
    Samuelsson, Jorgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Forssen, 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. Uppsala University, Sweden.
    Enhanced interpretation of adsorption data generated by liquid chromatography and by modern biosensors2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, p. 22-31Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Lakade, Sameer S.
    et al.
    Universitat Rovira i Virgili, ESP.
    Borrull, Francesc
    Universitat Rovira i Virgili, ESP.
    Furton, Kenneth G.
    Florida International University, USA.
    Kabir, Abuzar
    Florida International University, USA.
    Marcé, Rosa Maria
    Universitat Rovira i Virgili, ESP.
    Fontanals, Núria
    Universitat Rovira i Virgili, ESP.
    Dynamic fabric phase sorptive extraction for a group of pharmaceuticals and personal care products from environmental waters2016In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1456, p. 19-26Article in journal (Refereed)
    Abstract [en]

    This paper describes for the first time the use of a new extraction technique, based on fabric phase sorptive extraction (FPSE). This new mode proposes the extraction of the analytes in dynamic mode in order to reduce the extraction time. Dynamic fabric phase sorptive extraction (DFPSE) followed by liquid chromatography-tandem mass spectrometry was evaluated for the extraction of a group of pharmaceuticals and personal care products (PPCPs) from environmental water samples. Different parameters affecting the extraction were optimized and best conditions were achieved when 50mL of sample at pH 3 was passed through 3 disks and analytes retained were eluted with 10mL of ethyl acetate. The recoveries were higher than 60% for most of compounds with the exception of the most polar ones (between 8% and 38%). The analytical method was validated with environmental samples such as river water and effluent and influent wastewater, and good performance was obtained. The analysis of samples revealed the presence of some PPCPs at low ngL−1 concentrations.

  • 32.
    Lesko, Marek
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Rzeszów University of Technology, Poland.
    Fornstedt, Torgny
    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).
    A closer study of overloaded elution bands and their perturbation peaks in ion-pair chromatography2022In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1682, article id 463491Article in journal (Refereed)
    Abstract [en]

    There is strong renewed interest in ion-pair chromatography (IPC) because of its great importance for separating new-generation biosimilar pharmaceuticals such as oligonucleotides. Due to the complexity of the IPC process, its mathematical modeling is challenging, especially in preparative mode. In a recent study, Leśko et al. (2021) developed a mathematical model for predicting, with good accuracy, overloaded concentration profiles for sodium benzenesulfonate, describing how the overloaded solute concentration profiles change from Langmuirian to complicated U-shaped, and then back again to Langmuirian profiles, with increasing concentration of the ion-pair reagent in the mobile phase. This study identifies and explains the underlying mechanism generating these complex peak shapes and band-shape transformations; this was only possible by visualizing and modeling the underlying equilibrium perturbations that occur upon injection in preparative IPC. In the 2021 study, the model was derived based on the concentration profiles obtained using a conventional UV detector principle, so the concentration gradients and perturbation zones of the mobile-phase components were not visualized. In this study, the necessary mechanistic information was obtained via complementary experiments combining two detection principles, i.e., refractive index detection and UV detection, with modeling efforts. The models correctly described the invisible equilibrium perturbations and how these formed internal gradients of the mobile-phase components. The models also explained the complex overloaded solute-band deformations reported in the recent study. In addition, a rule of thumb was developed for predicting experimental conditions that could result in deformed solute elution profiles and/or for avoiding these deformations. The latter is crucial for the practical chromatographer, since such U-shaped solute-band profiles are undesirable in preparative separation due to the broader elution zones, resulting in lower productivity than that of normal band shapes.

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  • 33.
    Lesko, Marek
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Rzeszów University of Technology, Poland.
    Jora, Manasses
    AstraZeneca, Sweden.
    Stavenhagen, Kathrin
    AstraZeneca, Sweden.
    Leek, Tomas
    AstraZeneca, Sweden.
    Czechtizky, Werngard
    AstraZeneca, Sweden.
    Fornstedt, Torgny
    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).
    Strategies for predictive modeling of overloaded oligonucleotide elution profiles in ion-pair chromatography2023In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1711, article id 464446Article in journal (Refereed)
    Abstract [en]

    Due to their potential for gene regulation, oligonucleotides have moved into focus as one of the preferred modalities modulating currently undruggable disease-associated targets. In the course of synthesis and storage of oligonucleotides a significant number of compound-related impurities can be generated. Purification protocols and analytical methods have become crucial for the therapeutic application of any oligonucleotides, be they antisense oligonucleotides (ASOs), small interfering ribonucleic acids (siRNAs) or conjugates. Ion-pair chromatography is currently the standard method for separating and analyzing therapeutic oligonucleotides. Although mathematical modeling can improve the accuracy and efficiency of ion-pair chromatography, its application remains challenging. Simple models may not be suitable to treat advanced single molecules, while complex models are still inefficient for industrial oligonucleotide optimization processes. Therefore, fundamental research to improve the accuracy and simplicity of mathematical models in ion-pair chromatography is still a necessity. In this study, we predict overloaded concentration profiles of oligonucleotides in ion-pair chromatography and compare relatively simple and more advanced predictive models. The experimental system consists of a traditional C18 column using (dibutyl)amine as the ion-pair reagent and acetonitrile as organic modifier. The models were built and tested based on three crude 16-mer oligonucleotides with varying degrees of phosphorothioation, as well as their respective n – 1 and (P = O)1 impurities. In short, the proposed models were suitable to predict the overloaded concentration profiles for different slopes of the organic modifier gradient and column load. 

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  • 34.
    Lesko, Marek
    et al.
    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).
    Glenne, Emelie
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, K.
    Rzeszów University of Technology, POL.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Predictions of overloaded concentration profiles in supercritical fluid chromatography2021In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1639, article id 461926Article in journal (Refereed)
    Abstract [en]

    Here, overloaded concentration profiles were predicted in supercritical fluid chromatography using a combined two-dimensional heat and mass transfer model. The heat balance equation provided the temperature and pressure profiles inside the column. From this the density, viscosity, and mobile phase velocity profiles in the column were calculated. The adsorption model is here expressed as a function of the density and temperature of the mobile phase. The model system consisted of a Kromasil Diol column packed with 2.2-µm particles (i.e., a UHPSFC column) and the solute was phenol eluted with neat carbon dioxide at three different outlet pressures and five different mobile phase flow rates. The proposed model successfully predicted the eluted concentration profiles in all experimental runs with good agreement even with high-density drops along the column. It could be concluded that the radial temperature and density gradients did not significantly influence the overloaded concentration elution profiles.

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  • 35.
    Lesko, Marek
    et al.
    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).
    Kaczmarski, Krzysztof
    Rzeszow Univ Technol, POL.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Experimental and theoretical investigation of high-concentration elution bands in ion-pair chromatography2021In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1656, article id 462541Article in journal (Refereed)
    Abstract [en]

    The effective separation of many solutes, including pharmaceuticals, can be performed using an ion-pair reagent (IPR) in the mobile phase. However, chromatographic separation and mathematical modelling are a challenge in ionpair chromatography (IPC), especially in preparative mode, due to the complicated chromatographic process. In this study, we present a retention mechanism and a mathematical model that predict overloaded concentration profiles in IPC using a system with X-Bridge C18 as stationary phase and tetrabutylammonium bromide in the 0 - 15 mM concentration range as the IPR. Two different mobile phases were used: (i) 15/85 [v/v] acetonitrile/water, (ii) 25/75 methanol/water. The model compounds were sodium salts of organic compounds with sulfonic acid functions. The analytical and preparative elution profiles were obtained for specified conditions. The analytical data were utilized to calculate the difference in electrical potential between the surface and bulk solution using firm electrostatic theory. In the preparative mode in a certain range of IPR concentrations, complicated U-shaped overloaded profiles were observed. In the other considered cases, Langmuir overloaded elution profiles were recorded. A multilayer adsorption model was derived, which is consistent with the dynamic ion exchange models. The model assumes that lipophilic IPR adsorbs on the stationary phase, creating charged active sites that serve as exchange sites for the solutes. The molecules of the solute can adsorb on the already formed IPR layer. It was also assumed that a subsequent layer of solute can form on the formed layer of complexes due to interactions between the solute molecules. The model takes into account the electrostatic attraction and repulsion of the molecules, depending on the considered situation. The proposed model allowed prediction of the overloaded concentration profiles with very good agreement for the model solute and followed the progression from Langmuirian, through U-shaped, to again Langmuirian profiles. 

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  • 36.
    Lesko, Marek
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013). Rzeszów University of Technology, POL.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Rzeszów University of Technology, POL.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Evaluating the advantages of higher heat conductivity in a recently developed type of core-shell diamond stationary phase particle in UHPLC2020In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1625, article id 461076Article in journal (Refereed)
    Abstract [en]

    In recent studies, the nature and magnitude of the temperature gradients developed in ultra-high pressure liquid chromatography (UHPLC), were found to be dependent on the heat conductivity properties of the column matrices, but also, on the principle used for controlling the temperature over the column. Here, we investigated the potential of using highly heat conductive diamond-based stationary phases (85 times higher than silica), for reducing the temperature gradients. The stationary phases investigated were a (i) Diamond Analytics FLARE column, based on particles comprised of a graphite core surrounded by a very thin diamond shell, and two silica hybrid columns: (ii) a core-shell silica Kromasil Eternity Shell column and (iii) a fully porous silica Kromasil Eternity XT column. Models were developed based on two-dimensional heat transfer theory and mass transfer theory, which were used to model the temperature profiles and the migration of an analyte band accounting for column efficiencies at different flow rates. For the silica-based columns, using water-controlled temperature mode, the temperature gradients along the column axes are suppressed whereas temperature gradients in the radial direction prevails resulting in decreased column efficiencies. Using these columns with air-controlled temperature mode, the radial temperature gradients are reduced whereas temperature gradients along the column prevails resulting in decreased retention times. With the Diamond FLARE column, there was no loss in column efficiency using the water-controlled temperature mode and the van Deemter curves are almost identical using both temperature control modes. Thus, for the Diamond FLARE column, in contrast to the silica-based columns, there are almost no losses of column efficiencies due to reduced radial temperature gradients independent on how the column temperature was controlled.

  • 37.
    Olsson, Jeanette
    et al.
    Karlstad University, Faculty of Technology and Science.
    Stegander, Filip
    Karlstad University, Faculty of Technology and Science.
    Marlin, Nicola
    Karlstad University, Faculty of Technology and Science.
    Wan, Hong
    Lead Generation and Physical Chemistry, AstraZeneca R&D, Mölndal, Sweden.
    Blomberg, Lars G.
    Karlstad University, Faculty of Technology and Science.
    Enantiomeric Separation of Omeprazole and its Metabolite 5-Hydroxymeprazole Using Non-aqueous Capillary Electrophoresis2006In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1129, no 2, p. 291-295Article in journal (Refereed)
  • 38.
    Pruim, Peter
    et al.
    Univ Amsterdam, Analyt Chem Grp, Vant Hoff Inst Mol Sci, NL-1090 GD Amsterdam, Netherlands..
    Ohman, Marcus
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
    Schoenmakers, Peter J.
    Univ Amsterdam, Analyt Chem Grp, Vant Hoff Inst Mol Sci, NL-1090 GD Amsterdam, Netherlands..
    Kok, Wim Th.
    Univ Amsterdam, Analyt Chem Grp, Vant Hoff Inst Mol Sci, NL-1090 GD Amsterdam, Netherlands..
    Methacrylate monolithic stationary phases for gradient elution separations in microfluidic devices2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 31, p. 5292-5297Article in journal (Refereed)
    Abstract [en]

    Methacrylate monolithic stationary phases were produced in fused-silica chips by UV initiation. Poly(butyl methacrylate-co-ethylene dimethacrylate) (BMA) and poly(lauryl methacrylate-co-ethylene dimethacrylate) (LMA) monoliths containing 30, 35 and 40% monomers were evaluated for the separation of peptides under gradient conditions. The peak capacity was used as an objective tool for the evaluation of the separation performance. LMA monoliths of the highest density gave the highest peak capacities (approximate to 40) in gradients of 15 min and all LMA monoliths gave higher peak capacities than the BMA monoliths with the same percentage of monomers. Increasing the gradient duration to 30 min did not increase the peak capacity significantly. However, running fast (5 min) gradients provides moderate peak capacities (approximate to 20) in a short time. Due to the system dead volume of 1 mu L and the low bed volume of the chip, early eluting peptides migrated over a significant part of the column during the dwell time under isocratic conditions. It was shown that this could explain an increased band broadening on the monolithic stationary phase materials used. The effect is stronger with BMA monoliths, which partly explains the inferior performance of this material with respect to peak capacity. The configuration of the connections on the chip appeared to be critical when fast analyses were performed at pressures above 20 bar. (C) 2011 Elsevier B.V. All rights reserved.

  • 39.
    Pusfitasari, Eka Dian
    et al.
    University of Helsinki, Finland.
    Ruiz-Jimenez, Jose
    University of Helsinki, Finland.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Besel, Vitus
    University of Helsinki, Finland.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Hartonen, Kari
    University of Helsinki, Finland.
    Riekkola, Marja-Liisa
    University of Helsinki, Finland.
    Assessment of physicochemical properties of sorbent materials in passive and active sampling systems towards gaseous nitrogen-containing compounds2023In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1703, article id 464119Article in journal (Refereed)
    Abstract [en]

    The adsorption and desorption behavior of volatile nitrogen-containing compounds in vapor phase by solid-phase microextraction Arrow (SPME-Arrow) and in-tube extraction (ITEX) sampling systems, were investigated experimentally using gas chromatography-mass spectrometry. Three different SPME-Arrow coating materials, DVB/PDMS, MCM-41, and MCM-41-TP and two ITEX adsorbents, TENAX-GR and MCM-41-TP were compared to clarify the selectivity of the sorbents towards nitrogen-containing compounds. In addition, saturated vapor pressures for these compounds were estimated, both experimentally and theoretically. In this study, the adsorption of nitrogen-containing compounds on various adsorbents fol-lowed the Elovich model well, while a pseudo-first-order kinetics model best described the desorption kinetics. Pore volume and pore sizes of the coating sorbents were essential parameters for the deter-mination of the adsorption performance for the SPME-Arrow sampling system. MCM-41-TP coating with the smallest pore size gave the slowest adsorption rate compared to that of DVB/PDMS and MCM-41 in the SPME-Arrow sampling system. Both adsorbent and adsorbate properties, such as hydrophobicity and basicity, affected the adsorption and desorption kinetics in SPME-Arrow system. The adsorption and desorption rates of studied C6H15N isomers in the MCM-41 and MCM-41-TP sorbent materials of SPME-Arrow system were higher for dipropylamine and triethylamine (branched amines) than for hexylamine (linear chain amines). DVB/PDMS-SPME-Arrow gave fast adsorption rates for the aromatic-ringed pyridine and o-toluidine. All studied nitrogen-containing compounds demonstrated high desorption rates with DVB/PDMS-SPME-Arrow. Chemisorption and physisorption were the sorption mechanisms in MCM-41-and MCM-41-TP-SPME-Arrow, but additional experiments are needed to confirm this. An active sampling technique ITEX gave comparable adsorption and desorption rates on the selective MCM-41-TP and univer-sal TENAX-GR sorbent materials for all the compounds studied. Vapor pressures of nitrogen-containing compounds were experimentally estimated by using retention index approach and these values were compared with the theoretical ones, calculated using the COnductor-like Screening MOdel for Real Sol-vent (COSMO-RS) model. Both values agreed well with those found in the literature proving that these methods can be successfully used in predicting VOC's vapor pressures, e.g. for the formation of secondary organic aerosols.

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  • 40.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Eiriksson, F. F.
    University of Iceland.
    Åsberg, Dennis
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Thorsteinsdóttir, M.
    University of Iceland.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Determining gradient conditions for peptide purification in RPLC with machine-learning-based retention time predictions2019In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1598, p. 92-100Article in journal (Refereed)
    Abstract [en]

    A strategy for determining a suitable solvent gradient in silico in preparative peptide separations is presented. The strategy utilizes a machine-learning–based method, called ELUDE, for peptide retention time predictions based on the amino acid sequences of the peptides. A suitable gradient is calculated according to linear solvent strength theory by predicting the retention times of the peptides being purified at three different gradient slopes. The advantage of this strategy is that fewer experiments are needed to develop a purification method, making it useful for labs conducting many separations but with limited resources for method development. The preparative separation of met-enkephalin and leu-enkephalin was used as model solutes on two stationary phases: XBridge C18 and CSH C18. The ELUDE algorithm contains a support vector regression and is pre-trained, meaning that only 10–50 peptides are needed to calibrate a model for a certain stationary phase and gradient. The calibration is done once and the model can then be used for new peptides similar in size to those in the calibration set. We found that the accuracy of the retention time predictions is good enough to usefully estimate a suitable gradient and that it was possible to compare the selectivity on different stationary phases in silico. The absolute relative errors in retention time for the predicted gradients were 4.2% and 3.7% for met-enkephalin and leu-enkephalin, respectively, on the XBridge C18 column and 2.0% and 2.8% on the CSH C18 column. The predicted retention times were also used as initial values for adsorption isotherm parameter determination, facilitating the numerical calculation of overloaded elution profiles. Changing the trifluoroacetic acid (TFA) concentration from 0.05% to 0.15% in the eluent did not seriously affect the error in the retention time predictions for the XBridge C18 column, an increase of 1.0 min (in retention factor, 1.3). For the CSH C18 column the error was, on average, 2.6 times larger. This indicates that the model needs to be recalibrated when changing the TFA concentration for the CSH column. Studying possible scale-up complications from UHPLC to HPLC such as pressure, viscous heating (i.e., temperature gradients), and stationary-phase properties (e.g., packing heterogeneity and surface chemistry) revealed that all these factors were minor to negligible. The pressure effect had the largest effect on the retention, but increased retention by only 3%. In the presented case, method development can therefore proceed using UHPLC and then be robustly transferred to HPLC.

  • 41.
    Samuelsson, Jörgen
    et al.
    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).
    Shalliker, Andrew
    Australia.
    Exogenous factors contributing to column bed heterogeneity: Part 1: Consequences of 'air' injections in liquid chromatography2015In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1406, p. 186-91Article in journal (Refereed)
    Abstract [en]

    It has been shown that not only the packing homogeneity, but also factors external to the column bed, such as, frits and distributors can have important effects on the column performance. This current communication is the first in a series focusing on the impact of exogenous factors on the column bed heterogeneity. This study is based on several observations by us and others that chromatographic runs often, for technical reasons, include more or less portions of air in the injections. It is therefore extremely important to find out the impact of air on the column performance, the reliability of the results derived from analyses where air was injected, and the effect on the column homogeneity. We used a photographic approach for visualising the air transport phenomena, and found that the air transport through the column is comprised of many different types of transport phenomena, such as laminal flow, viscous fingering like flows, channels and bulbs, and pulsations. More particularly, the air clouds within the column definitely interact in the adsorption, i.e. mobile phase adsorbed to the column surface is displaced. In addition, irrespective of the type of air transport phenomena, the air does not penetrate the column homogeneously. This process is strongly flow dependent. In this work we study air transport both in an analytical scale and a semi-prep column.

  • 42.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Undin, Torgny
    Uppsala University.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Expanding the elution by characteristic point method for determination of various types of adsorption isotherms2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 24, p. 3737-3742Article in journal (Refereed)
    Abstract [en]

    Important improvements have recently been made on the elution by characteristic point (ECP) method to increase the accuracy of the determined adsorption isotherms. However, the method has so far been limited/used for only type I adsorption isotherms (e.g. Langmuir, Tóth, bi-Langmuir). In this study, general strategies are developed to expand the ECP method for the determination of more complex adsorption isotherms including such containing inflection points. We will exemplify the methodology with type II, type III and type V isotherms. Guidelines are given for how to determine such isotherms using the ECP method and for the experimental considerations that must be taken into account or that may be eliminated in the particular case.

  • 43.
    Samuelsson, Jörgen
    et al.
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Undin, Torgny
    Uppsala University, Sweden.
    Törncrona, Anders
    Eka Chemicals AB, Sweden.
    Fornstedt, Torgny
    Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
    Improvement in the generation of adsorption isotherm data in the elution by characteristic points method-: the ECP-slope approach2010In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, no 46, p. 7215-7221Article in journal (Refereed)
    Abstract [en]

    The elution by characteristic points (ECP) method is a very rapid and precise method for determination of the phase system equilibrium of phase systems in broad solute concentration ranges. Thus, the method is especially suitable for rapid characterization of high efficient separation systems. One important source of error, the effects by the post-loop dispersion, was eliminated in a recent investigation. In this study, the systematic error caused by the selection of the integration starting point at concentration equal to 0 is eliminated. This is done by developing and validating a new procedure for isotherm data generation; the ECP-slope method. The method generates raw slope data of the adsorption isotherm instead of raw adsorption data by integrations as the classical ECP does. Both numerical and experimental data were used for the comparison of the classical ECP approach with the slope-ECP method

  • 44.
    Zhang, Xiaoou
    et al.
    Department of Biological Science and Technology, School of Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, 116024, China.
    Samuelsson, Jörgen
    Uppsala universitet, Institutionen för fysikalisk och analytisk kemi.
    Janson, Jan-Christer
    Uppsala universitet, Institutionen för fysikalisk och analytisk kemi.
    Wang, Changhai
    Department of Biological Science and Technology, School of Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, 116024, China..
    Su, Zhiguo
    National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Box 353, Beijing, 100190, China.
    Gu, Ming
    National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Box 353, Beijing, 100190, China.
    Fornstedt, Torgny
    Uppsala universitet, Institutionen för fysikalisk och analytisk kemi.
    Investigation of the adsorption behavior of glycine peptides on 12% cross-linked agarose gel media2010In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, no 12, p. 1916-1925Article in journal (Refereed)
    Abstract [en]

    The highly cross-linked 12% agarose gel Superose 12 10/300 GL Causes retardation of glycine peptides when mobile phases containing varying concentrations of acetonitrile in water are used An investigation has been made into the retention mechanism behind this retardation using the glycine dipeptide (GG) and tripeptide (GGG) as models The dependence of retention times of analytical-size peaks Under different experimental conditions was interpreted such that the adsorption most probably was caused by the formation of hydrogen bonds but that electrostatic interactions cannot be ruled Out Thereafter, a nonlinear adsorption study Was undertaken at different acetonitrile content in the eluent, using the elution by characteristic points (ECPs) method on strongly overloaded GG and GGG peaks With a new evaluation tool, the adsorption energy distribution (AED) Could be calculated prior to the model selection These calculations revealed that when the acetonitrile content in the eluent was varied from 0% to 20% the interactions turned from (i) being homogenous (GG) or mildly heterogeneous (GGG), (ii) via a more or less stronger degree of heterogeneity around one site to (iii) finally a typical bimodal energy interaction comprising of two sites (GG at 20% and GGG at 10% and 20%) The Langmuir, Toth and bi-Langmuir models described these interesting adsorption trends excellently Thus, the retardation observed for these glycine peptides is interpreted as being of mixed-mode character composed of electrostatic bonds and hydrogen bonds.

  • 45.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Chutkowski, Marcin
    Rzeszów University of Technology, Polen.
    Leśko, Marek
    Rzeszów University of Technology, Polen.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Rzeszów University of Technology, Polen.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    A practical approach for predicting retention time shifts due to pressure and temperature gradients in ultra-high-pressure liquid chromatography2017In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1479, p. 107-120Article in journal (Refereed)
    Abstract [en]

    Large pressure gradients are generated in ultra-high-pressure liquid chromatography (UHPLC) using sub–2 μm particles causing significant temperature gradients over the column due to viscous heating. These pressure and temperature gradients affect retention and ultimately result in important selectivity shifts. In this study, we developed an approach for predicting the retention time shifts due to these gradients. The approach is presented as a step-by-step procedure and it is based on empirical linear relationships describing how retention varies as a function of temperature and pressure and how the average column temperature increases with the flow rate. It requires only four experiments on standard equipment, is based on straightforward calculations, and is therefore easy to use in method development. The approach was rigorously validated against experimental data obtained with a quality control method for the active pharmaceutical ingredient omeprazole. The accuracy of retention time predictions was very good with relative errors always less than 1% and in many cases around 0.5% (n = 32). Selectivity shifts observed between omeprazole and the related impurities when changing the flow rate could also be accurately predicted resulting in good estimates of the resolution between critical peak pairs. The approximations which the presented approach are based on were all justified. The retention factor as a function of pressure and temperature was studied in an experimental design while the temperature distribution in the column was obtained by solving the fundamental heat and mass balance equations for the different experimental conditions. We strongly believe that this approach is sufficiently accurate and experimentally feasible for this separation to be a valuable tool when developing a UHPLC method. After further validation with other separation systems, it could become a useful approach in UHPLC method development, especially in the pharmaceutical industry where demands are high for robustness and regulatory oversight.

  • 46.
    Åsberg, Dennis
    et al.
    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).
    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.

  • 47.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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 (from 2013).
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    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 (from 2013).
    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.

  • 48.
    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.

  • 49.
    Åsberg, Dennis
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Leśko, Marek
    Department of Chemical Engineering, Rzeszów University of Technology, PL-35 959 Rzeszów, Poland.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Kaczmarski, Krzysztof
    Department of Chemical Engineering, Rzeszów University of Technology, PL-35 959 Rzeszów, Poland.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Method transfer from high-pressure liquid chromatography to ultra-high-pressure liquid chromatography. I. A thermodynamic perspective2014In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1362, p. 206-217Article in journal (Refereed)
    Abstract [en]

    This is the first investigation in a series that aims to enhance the scientific knowledge needed for reliable analytical method transfer between HPLC and UHPLC using the quality by design (QbD) framework. Here, we investigated the differences and similarities from a thermodynamic point of view between RP-LC separations conducted with 3.5 μm (HPLC) and 1.7 μm (UHPLC) C18 particles. Three different model solutes and one pharmaceutical compound were used: the uncharged cycloheptanone, the cationic benzyltriethylammonium chloride, the anionic sodium 2-naphatlene sulfonate and the pharmaceutical compound omeprazole, which was anionic at the studied pH. Adsorption data were determined for the four solutes at varying fractions of organic modifier and in gradient elution in both the HPLC and UHPLC system, respectively. From the adsorption data, the adsorption energy distribution of each compound was calculated and the adsorption isotherm model was estimated. We found that the adsorption energy distribution was similar, with only minor differences in degree of homogeneity, for HPLC and UHPLC stationary phases. The adsorption isotherm model did not change between HPLC and UHPLC, but the parameter values changed considerably especially for the ionic compounds. The dependence of the organic modifier followed the same trend in HPLC as in UHPLC. These results indicates that the adsorption mechanism of a solute is the same on HPLC and UHPLC stationary phases which simplifies design of a single analytical method applicable to both HPLC and UHPLC conditions within the QbD framework.

  • 50.
    Åsberg, Dennis
    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.
    A fundamental study of the impact of pressure on the adsorption mechanism in reversed-phase liquid chromatography2016In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1457, p. 97-106Article in journal (Refereed)
    Abstract [en]

    A fundamental investigation of the pressure effect on individual adsorption sites was undertaken based on adsorption energy distribution and adsorption isotherm measurements. For this purpose, we measured adsorption equilibrium data at pressures ranging from 100 to 1000 bar at constant flow and over a wide concentration range for three low-molecular-weight solutes, antipyrine, sodium 2-naphthalenesulfonate, and benzyltriethylammonium chloride, on an Eternity C18 stationary phase. The adsorption energy distribution was bimodal for all solutes, remaining clearly so at all pressures. The bi-Langmuir model best described the adsorption in these systems and two types of adsorption sites were identified, one with a low and another with a high energy of interaction. Evidence exists that the low-energy interactions occur at the interface between the mobile and stationary phases and that the high-energy interactions occur nearer the silica surface, deeper in the C18 layer. The contribution of each type of adsorption site to the retention factor was calculated and the change in solute molar volume from the mobile to stationary phase during the adsorption process was estimated for each type of site. The change in solute molar volume was 2-4 times larger at the high-energy site, likely because of the greater loss of solute solvation layer when penetrating deeper into the C18 layer. The association equilibrium constant increased with increasing pressure while the saturation capacity of the low-energy site remained almost unchanged. The observed increase in saturation capacity for the high-energy site did not affect the column loading capacity, which was almost identical at 50- and 950-bar pressure drops over the column. (C) 2016 Elsevier B.V. All rights reserved.

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