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Combining Chemometric Models with Adsorption Isotherm Measurements to Study Omeprazole in RP-LC
Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).ORCID-id: 0000-0001-8561-6872
Rzeszów University of Technology, Poland.
Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).ORCID-id: 0000-0003-1819-1709
AstraZeneca R&D Gothenburg, Mölndal.
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2016 (Engelska)Ingår i: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 79, nr 19, s. 1283-1291Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The adsorption of the proton-pump inhibitor omeprazole was investigated using RP-LC with chemometric models combined with adsorption isotherm modelling to study the effect of pH and type of organic modifier (i.e., acetonitrile or methanol). The chemometric approach revealed that omeprazole was tailing with methanol and fronting with acetonitrile along with increased fronting at higher pH. The increased fronting with higher pH for acetonitrile was explored using a pH-dependent adsorption isotherm model that was determined using the inverse method and it agreed well with the experimental data. The model indicated that the peaks exhibit more fronting at high pH due to a larger fraction of charged omeprazole molecules. This model could accurately predict the shape of elution profiles at arbitrary pH levels in the studied interval. Using a two-layer adsorption isotherm model, the difference between acetonitrile and methanol was studied at the lowest pH at which almost all omeprazole molecules are neutral. Omeprazole had adsorbate–adsorbate interactions that were similar in strength for the acetonitrile and methanol mobile phases, while the solute–adsorbent interactions were almost twice as strong with methanol. The difference in the relative strengths of these two interactions likely explains the different peak asymmetries (i.e., tailing/fronting) in methanol and acetonitrile. In conclusion, thermodynamic modelling can complement chemometric modeling in HPLC method development and increase the understanding of the separation.

Ort, förlag, år, upplaga, sidor
Springer Berlin/Heidelberg, 2016. Vol. 79, nr 19, s. 1283-1291
Nyckelord [en]
HPLC, pH, Adsorption, Omeprazole
Nationell ämneskategori
Analytisk kemi
Forskningsämne
Kemi
Identifikatorer
URN: urn:nbn:se:kau:diva-47561DOI: 10.1007/s10337-016-3151-8ISI: 000387326400007OAI: oai:DiVA.org:kau-47561DiVA, id: diva2:1060869
Forskningsfinansiär
KK-stiftelsen, 20140179ÅForsk (Ångpanneföreningens Forskningsstiftelse), 15/497Vetenskapsrådet, 2015-04627Tillgänglig från: 2016-12-30 Skapad: 2016-12-30 Senast uppdaterad: 2018-11-22Bibliografiskt granskad
Ingår i avhandling
1. Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
Öppna denna publikation i ny flik eller fönster >>Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Karlstad: Karlstads universitet, 2017. s. 75
Serie
Karlstad University Studies, ISSN 1403-8099 ; 2017:9
Nyckelord
Liquid chromatography, UHPLC, Pharmaceutical analysis, Adsorption isotherm, Design of experiments, Quality control
Nationell ämneskategori
Analytisk kemi
Forskningsämne
Kemi
Identifikatorer
urn:nbn:se:kau:diva-47852 (URN)978-91-7063-756-8 (ISBN)978-91-7063-757-5 (ISBN)
Disputation
2017-04-06, 9C204, Rejmersalen, Karlstads universitet, Universitetsgatan 2, Karlstad, 10:00 (Engelska)
Opponent
Handledare
Forskningsfinansiär
Vetenskapsrådet, 2015-04627ÅForsk (Ångpanneföreningens Forskningsstiftelse), 15/497
Tillgänglig från: 2017-03-08 Skapad: 2017-02-10 Senast uppdaterad: 2019-06-10Bibliografiskt granskad

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