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Method transfer from high-pressure liquid chromatography to ultra-high-pressure liquid chromatography. I. A thermodynamic perspective
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.
Department of Chemical Engineering, Rzeszów University of Technology, PL-35 959 Rzeszów, Poland.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.ORCID iD: 0000-0003-1819-1709
Department of Chemical Engineering, Rzeszów University of Technology, PL-35 959 Rzeszów, Poland.
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2014 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1362, 206-217 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2014. Vol. 1362, 206-217 p.
Keyword [en]
Adsorption isotherm, Gradient elution, HPLC, Omeprazole., Quality by design, UHPLC
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kau:diva-34383DOI: 10.1016/j.chroma.2014.08.051ISI: 000342530600021PubMedID: 25189333OAI: oai:DiVA.org:kau-34383DiVA: diva2:755876
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2017-02-10Bibliographically approved
In thesis
1. Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
Open this publication in new window or tab >>Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis, e.g. quality control, has accelerated in recent years and there is currently a mix of HPLC and UHPLC instrumentation within pharmaceutical companies. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production.

Using chromatographic modelling and fundamental theory, this thesis investigated method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved methods to support efficient life cycle management.

The higher pressure in UHPLC gave a retention increase of up to 40% as compared to conventional HPLC while viscous heating, instead, reduced retention and the net result was very solute dependent. Selectivity shifts were observed even between solutes with similar structure when switching between HPLC and UHPLC and an experimental method to predict such selectivity shifts was therefore developed. The peak shape was negatively affected by the increase in pressure for some solutes since secondary interactions between the solute and the stationary phase increased with pressure.

With the upcoming ICH Q12 guideline, it will be possible for the industry to convert existing methods to UHPLC in a more flexible way using the deeper understanding and the regulatory concept presented here as a case example.

Abstract [en]

Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to conventional HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis has accelerated in recent years and currently both instruments are used. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production. In UHPLC, the column is packed with smaller particles than in HPLC resulting in higher pressure and viscous heating. Both the higher pressure and the higher temperature may cause changes in retention and selectivity making method conversion unpredictable.

Using chromatographic modelling and fundamental theory, this thesis investigates method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved quality control methods and how predicable method conversion is achieved by improved understanding.

Place, publisher, year, edition, pages
Karlstad: Karlstads universitet, 2017. 75 p.
Series
Karlstad University Studies, ISSN 1403-8099 ; 2017:9
Keyword
Liquid chromatography, UHPLC, Pharmaceutical analysis, Adsorption isotherm, Design of experiments, Quality control
National Category
Analytical Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-47852 (URN)978-91-7063-756-8 (ISBN)978-91-7063-757-5 (ISBN)
Public defence
2017-04-06, 9C204, Rejmersalen, Karlstads universitet, Universitetsgatan 2, Karlstad, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 2015-04627ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 15/497
Available from: 2017-03-08 Created: 2017-02-10 Last updated: 2017-03-15Bibliographically approved

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