SELECTION OF STATIONARY PHASES FOR THE LIQUID-CHROMATOGRAPHIC ANALYSIS OF BASIC COMPOUNDS USING CHEMOMETRIC METHODS

The analysis of basic compounds by means of reversed-phase liquid chromatography is often hampered by poor peak shapes. In this paper chemometrical methods are used to select and reduce the number of test compounds and to detect differences in applicability of stationary phases designed for the analysis of basic drugs. In the first part principal component analysis was applied to reduce the number of test compounds necessary to characterize a stationary phase. From a data set of the asymmetry values of 32 test compounds analyzed on six different LC columns, five representative compounds were selected. Subsequently, these five compounds were used for evaluation of commercially available columns. For the column judgement the asymmetry of the test compounds, the efficiency and the short-term reproducibility of the capacity factor and the plate number, were taken into account. Graphical presentation using bar charts, multi-criteria decision making based on the Pareto optimality and bi-plots were used to distinguish between columns. First of all eight columns were compared at individual pH values of 3.0, 7.0 and 11.0. Finally, all results were combined and revealed that for our test compounds very good results were obtained at a pH of 11 using a column containing zirkonium oxide particles coated with polybutadiene (3MZ-18). At low pH values good results were obtained with a Supelcosil LC-ABZ and a Zorbax Rx-C-18 column. Overall it can be concluded that a chemometric approach is successfully applied for the development of a method for in-house column testing and evaluation dedicated to the Organon type of compounds. Other columns developed for the analysis of basic solutes can now be efficiently tested with the method described in this paper. Chemometric methods were useful to efficiently reduce the number of test compounds and for column evaluation. However, the final selection of a column also depends on the special requirements defined by the expert. The requirements, which are, for example, for routine quality control clearly different than for purity testing of new chemical entities in drug development, can be translated to weighing factors for the variables tested. For this the advice of the expert remains indispensable.