Da Doornbos

Comparison of optimization methods in reversed-phase high-performance liquid chromatography using mixture designs and multi-criteria decision making

Abstract The optimization of different mobile phase systems is compared using statistical mixture designs. Isoeluotropic and non-isoeluotropic ternary and quaternary mobile phase mixtures have been optimized with regard to selectivity and analysis time. For a sample consisting of six benzene derivatives, the logarithm of the capacity factor of each solute is modelled in a full quaternary mobile phase system consisting of water and three organic modifiers. From the models, different separation criteria such as the resolution or selectivity of the worst separated pair of peaks, i.e. , the Min Res or Min Alpha, respectively, are calculated. Also, the capacity factor of the last peak, the Max k , can be predicted as a measure of analysis time. Response surfaces that show the different criteria as function of the different mobile phase systems re plotted and evaluated by multi-criteria decision making (MCDM). It is concluded that the optimization of isoeluotropic ternary mobile phase systems consisting of mixtures of two pseudo-components of equal solvent strength is inferior to that of iseluotropic quaternary mobile phase systems consisting of mixtures of three pseudo-components of equal solvent strength or to that of non-isoeluotropic ternary systems consisting of mixtures of water and two organic modifiers. The latter two optimization methods do not guarantee that the global maximum with respect to the Min Res of the full quaternary system consisting of mixtures of water and three organic modifiers will be found. On the one hand, the isoeluotropic quaternary system does not use variation of the water fraction to influence the selectivity. On the other, a mixture of three modifiers and water may provide a wider range of selectivity than mixture of two modifiers and water. Both optimization methods predict and realize a good separation of a test sample in a short analysis time provided that the solvent strength of the isoeluotropic quaternary system is properly chosen.

Optimization of the reversed-phase high-performance liquid chromatographic separation of synthetic estrogenic and progestogenic steroids using the multi-criteria decision making method

The optimization of the reversed-phase high-performance liquid chromatographic separation of a mixture of ethynylestradiol, desogestrel and three related compounds is described. A procedure is used that allows the prediction of the capacity factors of each individual synthetic steroid, depending on the mobile phase composition. Therefore, complete chromatograms can be predicted and evaluated with the multi-criteria decision making method.

DEVELOPMENT AND OPTIMIZATION OF PHARMACEUTICAL FORMULATIONS USING A SIMPLEX LATTICE DESIGN

The composition of pharmaceutical formulations is often subject to trial and error. This approach is time consuming and unreliable in finding the best formulation. Optimization by means of an experimental design might be helpful in shortening experimenting time. Such a design with the concomitant mathematical models, reveals effects and interactions of the variables. The independent variables are the different compositions of the mixtures of the chosen ingredients [drug(s) and excipients]. The dependent variables are the properties (responses) of the formulation. When all responses of interest have been expressed in models that describe the response as a function of the composition of the mixture, the models can be combined graphically or mathematically to find a composition satisfying all demands. In this paper an introduction to the use of mixture designs will be given by means of a theoretical part and an example: optimizing a tablet formulation consisting of excipients only.

Utility functions as optimization criteria for separations by high-performance liquid chromatography

Abstract Several response functions have been proposed as optimization criteria for sequential optimization methods in chromatography. Studies of their behaviour indicate that several unresolved problems are associated with the use of these criteria for optimization purposes. All the proposed criteria suffer from the disadvantage that they do not give an unequivocal optimum. The present study illustrates this for some of the proposed criteria by actually mapping the response surface for several separations in a ternary mobile phase on a reversed-phase column.

Multivariate characterization of solvent strength and solvent selectivity in reversed-phase high-performance liquid chromatography

Abstract Principal component analysis was used to determine the dimensionality and structure of three data sets consisting of the capacity factors of eleven to twenty different solutes measured in nine different mobile phase compositions consisting of water and methanol and/or acetonitrile on three reversed-phase columns. Principal component analysis showed that two principal components could account for the total variance in the data and that the percentage variance explained by the first principal component (about 80–95%) was much greater than the percentage explained by the second principal component, but that the percentage depended strongly on the choice of solutes for the sample. The first principal component could be associated with solvent strength and solvent strength selectivity and the second principal component with modifier selectivity. Solutes that showed strong modifier selectivity could be distinguished from solutes that have almost zero modifier selectivity, which could be useful for the definition of an empirical solvent strength scale.

Chemometrics in bioanalytical sample preparation : a fractionated combined mixture and factorial design for the modelling of the recovery of five tricyclic amines from plasma after liquid-liquid extraction prior to high-performance liquid chromatography

A general systematic approach is described for the chemometric modelling of liquid-liquid extraction data of drugs from biological fluids. Extraction solvents were selected from Snyders solvent selectivity triangle: methyl tert.-butyl ether, methylene chloride and chloroform. The composition of a mixture of the three extraction solvents was varied and the extraction yield (recovery) of a group of tricyclic amines was measured at all compositions selected. Two process variables, the extraction time and the extraction intensity, were varied simultaneously with the mixture variables to study their influence and their interaction with the mixture composition. The combined mixture and factorial design statistical techniques obtained in this way enabled the recovery to be modelled as a function of both the composition of the extraction liquid and the process variables. The models were assessed with regard to both descriptive and predictive capacities. The results showed that structurally related compounds may demonstrate different partitioning behaviour with regard to both mixture variables and process variables. It was concluded that mixtures of solvents result in higher extraction efficiencies for the amines. A positive effect on the extraction efficiency was demonstrated by the extraction intensity process variable and extraction time. A positive effect on the extraction efficiency was demonstrated by an interaction between extraction intensity and time. Mixture models in which process variables were introduced were recognized as being very suitable for modelling liquid-liquid extraction systems.

The automatic optimization of separations in high-performance liquid chromatography

Abstract Various quality criteria for chromatographic separations have been suggested, but none of them seems to be useful in the automatic optimization of separations by high-performance liquid chromatography. A different optimization strategy is considered: mathematical relations between parameters from the chromatogram and the solvent composition are established. By using one or more of these relations, the optimal composition of the liquid phase can be predicted for particular separations.

IDENTIFICATION OF MIXTURES OF SYNTHETIC ORGANIC PIGMENTS USING UV-VIS SPECTROPHOTOMETRY AND KALMAN FILTERING

Abstract A Kalman filter is used to determine the number of components and their concentrations in mixtures of synthetic organic pigments. In this way, a quantitative identification of mixtures of these pigments is possible as is shown with a simulated as well a real mixture. The dataset used in the experiments, consisted of as much as 27 candidate pigments.

THE IMPROVEMENT OF SIMCA CLASSIFICATION BY USING KERNEL DENSITY-ESTIMATION .2. PRACTICAL EVALUATION OF SIMCA, ALLOC AND CLASSY ON 3 DATA SETS

Abstract The performance of the new probabilistic classification method CLASSY is evaluated on three different data sets, together with its predecessors SIMCA and ALLOC. The improvement made over ALLOC is only marginal, whereas CLASSY shows better predictive ability and greater reliability than SIMCA in most cases.

INTRODUCTION OF A ROBUSTNESS COEFFICIENT IN OPTIMIZATION PROCEDURES - IMPLEMENTATION IN MIXTURE DESIGN-PROBLEMS .2. SOME PRACTICAL CONSIDERATIONS

The influence of a number of parameters on the behaviour of the robustness coefficient, introduced in Part I, is considered here using an artificial data set. The application of this robustness coefficient with multi-criteria decision making is demonstrated with a real data set.