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Microemulsion electrokinetic chromatography of drugs varying in charge and hydrophobicity: II. Strategies for optimisation of separation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
2004 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 25, no 12, 1792-1809 p.Article in journal (Refereed) Published
Abstract [en]

The separation of anionic, cationic, and neutral drugs in microemulsion electrokinetic chromatography (MEEKC) was studied. The concentration of sodium dodecyl sulfate (SDS; surfactant) and 2-propanol (organic solvent) was varied in a three-level full factorial design. 29 different model substances were chosen with different hydrophobicities and charges (neutral, positive, and negative). The models were calculated by means of multiple linear regression (MLR). The compounds were divided into five different subgroups, and different strategies for optimization of the separation within each group were investigated. The optimization was done by maximizing the selectivity using response surface plots in MODDE, by calculation of different chromatographic functions, and by using the software DryLab. For all the different groups, MODDE, almost all chromatographic functions and DryLab gave approximately the same settings of the factors for optimum separation. Attempts were made to fit descriptors of the compounds to the retention data from the three-level full factorial design by means of partial least squares projection to latent structures (PLS). Between 86 and 89% of all predictions of migration times were acceptable (80-120% of the observed value).

Place, publisher, year, edition, pages
2004. Vol. 25, no 12, 1792-1809 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-91002DOI: 10.1002/elps.200305812PubMedID: 15213977OAI: oai:DiVA.org:uu-91002DiVA: diva2:163561
Available from: 2003-11-06 Created: 2003-11-06 Last updated: 2013-07-05Bibliographically approved
In thesis
1. Aspects of Optimisation of Separation of Drugs by Chemometrics
Open this publication in new window or tab >>Aspects of Optimisation of Separation of Drugs by Chemometrics
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Statistical experimental designs have been used for method development and optimisation of separation. Two reversed phase HPLC methods were optimised. Parameters such as the pH, the amount of tetrabutylammonium (TBA; co-ion) and the gradient slope (acetonitrile) were investigated and optimised for separation of erythromycin A and eight related compounds. In the second method, a statistical experimental design was used, where the amounts of acetonitrile and octane sulphonate (OSA; counter ion) and the buffer concentration were studied, and generation of an α-plot with chromatogram simulations optimised the separation of six analytes.

The partial filling technique was used in capillary electrophoresis to introduce the chiral selector Cel7A. The effect of the pH, the ionic strength and the amount of acetonitrile on the separation and the peak shape of R- and S-propranolol were investigated.

Microemulsion electrokinetic chromatography (MEEKC) is a technique similar to micellar electrokinetic chromatography (MEKC), except that the microemulsion has a core of tiny droplets of oil inside the micelles. A large number of factors can be varied when using this technique. A screening design using the amounts of sodium dodecyl sulphate (SDS), Brij 35, 1-butanol and 2-propanol, the buffer concentration and the temperature as factors revealed that the amounts of SDS and 2-propanol were the most important factors for migration time and selectivity manipulation of eight different compounds varying in charge and hydrophobicity. SDS and 2-propanol in the MEEKC method were further investigated in a three-level full factorial design analysing 29 different compounds sorted into five different groups. Different optimisation strategies were evaluated such as generating response surface plots of the selectivity/resolution of the most critical pair of peaks, employing chromatographic functions, simplex optimisation in MODDE and 3D resolution maps in DryLab™.

Molecular descriptors were fitted in a PLS model to retention data from the three-level full factorial design of the MEEKC system. Two different test sets were used to study the predictive ability of the training set. It was concluded that 86 – 89% of the retention data could be predicted correctly for new molecules (80 – 120% of the experimental values) with different settings of SDS and 2-propanol.

Statistical experimental designs and chemometrics are valuable tools for the development and optimisation of analytical methods. The same chemometric strategies can be employed for all types of separation techniques.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 75 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 300
Pharmaceutical chemistry, optimisation, separation, chemometrics, high performance liquid chromatography, electrodriven techniques, microemulsion electrokinetic chromatography, statistical experimental design, molecular modelling, chiral separation, cellobiohydrolase, Farmaceutisk kemi
National Category
Medicinal Chemistry
urn:nbn:se:uu:diva-3738 (URN)91-554-5778-9 (ISBN)
Public defence
2003-11-28, B41, Uppsala Biomedical Centre, Uppsala, 13:15
Available from: 2003-11-06 Created: 2003-11-06Bibliographically approved

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