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Optimization strategies accounting for the additive in preparative chiral liquid chromatography
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
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2012 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1269, no SI, 279-286 p.Article in journal (Refereed) Published
Abstract [en]

This study is an in-depth investigation on how numerical optimization strategies that also account for the additive type and concentration, in preparative batch chromatography, should be performed. As a model 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 acetic acid or hexanoic acid in methanol. The inverse method was used to determine the competitive adsorption isotherm parameters for the enantiomers and the additives. Three different optimization strategies were examined: (1) injection volume optimization, (2) optimization of injection volume and additive concentration, and (3) full optimization including injection volume, additive concentration, sample concentration and flow rate. It was concluded that (i) it is important to incorporate the additive concentration in the optimization procedure to achieve the highest production rates, (ii) the full optimization strategy had the overall best results, and (iii) the selection of additive is very important (here acetic acid additive was superior to the hexanoic acid additive). By including the additive in the adsorption model and in the numerical optimization it is not only possible to achieve higher production rates but also to properly select the additive that is most advantageous for the specific separation problem.

Place, publisher, year, edition, pages
2012. Vol. 1269, no SI, 279-286 p.
Keyword [en]
Additive, Chiral preparative Chromatography, Enantiomers, Inverse method, Optimization, Acid additives, Additive concentrations, Adsorption model, Aminobutyric acids, Batch chromatography, Chiral liquid chromatography, Chiral stationary phase, Competitive adsorption isotherms, Full optimization, Hexanoic acids, In-depth investigation, Injection volume, Inverse methods, Model system, Numerical optimizations, Optimization procedures, Optimization strategy, Production rates, Sample concentration, Separation problems, Acetic acid, Adsorption, Amino acids, Chirality, Inverse problems, Liquid chromatography, Methanol, pH, Saturated fatty acids, Separation, Additives, 2 aminobutyric acid, carbamic acid, hexanoic acid, quinidine, adsorption kinetics, article, chemical composition, chiral chromatography, concentration (parameters), elution, enantiomer, flow rate, ion exchange, priority journal, process optimization, reaction time, separation technique
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-192063DOI: 10.1016/j.chroma.2012.05.052ISI: 000312475300023OAI: oai:DiVA.org:uu-192063DiVA: diva2:589274
Available from: 2013-01-17 Created: 2013-01-15 Last updated: 2014-04-29Bibliographically approved
In thesis
1. Adsorption Studies with Liquid Chromatography: Experimental Preparations for Thorough Determination of Adsorption Data
Open this publication in new window or tab >>Adsorption Studies with Liquid Chromatography: Experimental Preparations for Thorough Determination of Adsorption Data
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Analytical chemistry is a field with a vast variety of applications. A robust companion in the field is liquid chromatography, the method used in this thesis, which is an established workhorse and a versatile tool in many different disciplines. It can be used for identification and quantification of interesting compounds generally present in low concentrations, called analytical scale chromatography. It can also be used for isolation and purification of high value compounds, called preparative chromatography. The latter is usually conducted in large scale with high concentrations. With high concentrations it is also possible to determine something called adsorption isotherms.

Determination of adsorption isotherms is a useful tool for quite a wide variety of reasons. It can be used for characterisation of chromatographic separation systems, and then gives information on the retention mechanism as well as provides the possibility to study column-column and batch-batch reproducibility. If a protein is immobilised on a solid support, adsorption isotherms can be used for pharmacological characterisation of drug-protein interactions. Moreover, they can be used for the study of unexpected chromatographic phenomena.

If the adsorption isotherm is known it is also possible to simulate chromatograms, and subsequently optimise the separation process numerically. The gain of a numerically optimised separation process is higher purity or yield of valuable compounds such as pharmaceuticals or antioxidants, as well as reducing the solvent usage. Taken all together, it saves time, money and the environment.

However, the process of the adsorption isotherm determination requires a number of careful experimental considerations and preparations, and these are the main focus of the thesis. Important steps along the way include the choice of separation system and of suitable analytes, preparation of mobile phases and sample solutions, calibration, determination of injection profiles and column void, and of course the adsorption isotherm determination method itself. It is also important to keep track of parameters such as temperature and pH. These issues are discussed in this thesis.

At the end, a description of useful methods for processing of the raw adsorption isotherm data is presented, as well as a brief passage on methods for numerical optimisation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 56 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1118
Liquid chromatography, HPLC, UHPLC, Reversed phase, Preparative chromatography, Adsorption isotherm, Injection profile, Sample pH, pH stable conditions, Peak deformation, Band distortion, Overloaded band, Chiral preparative chromatography
National Category
Chemical Sciences Analytical Chemistry
Research subject
Analytical Chemistry
urn:nbn:se:uu:diva-216235 (URN)978-91-554-8858-1 (ISBN)
Public defence
2014-03-14, B22, BMC, Husargatan 3, Uppsala, 10:15 (English)
Available from: 2014-02-14 Created: 2014-01-20 Last updated: 2014-04-29

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