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A practical approach for predicting retention time shifts due to pressure and temperature gradients in ultra-high-pressure liquid chromatography
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.ORCID iD: 0000-0001-8561-6872
Rzeszów University of Technology, Polen.
Rzeszów University of Technology, Polen.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences.ORCID iD: 0000-0003-1819-1709
Show others and affiliations
2017 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1479, 107-120 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 1479, 107-120 p.
Keyword [en]
Gradient effects, Method development, Pressure effects, Retention time, Temperature, UHPLC
National Category
Analytical Chemistry
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:kau:diva-47559DOI: 10.1016/j.chroma.2016.11.050PubMedID: 27986288OAI: oai:DiVA.org:kau-47559DiVA: diva2:1060876
Funder
Knowledge Foundation, 20150233ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 15/497Swedish Research Council, 2015-04627
Available from: 2016-12-30 Created: 2016-12-30 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: 2017-06-30Bibliographically approved

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