Towards a general approach for the impurity profiling of drugs by micellarelectrokinetic chromatography

A general micellar electrokinetic chromatographic (MEKC) strategy for the i mpurity profiling of drugs was developed involving a sodium dodecyl sulfate (SDS) and a cetyltrimethylammonium bromide (CTAB) MEKC system. With this c ombination, in principle, each sample component passes the detector in at l east one of the two MEKC systems provided that separation buffers of the sa me pH are used in both systems. In order to select the proper MEKC systems, the electroosmotic flow (EOF) and micelle migration time (tmc) were determ ined for separation buffers of several pH values, containing various amount s of surfactant and organic modifier. The selectivity of the MEKC systems w as studied using a mixture of compounds with a wide range of physico-chemic al properties. The final selection of two adequate MEKC systems for this ap proach was based on the requirements that the t(mc) (i.e., analysis time) o f both systems was below 20 min and that the t(mc)/t(eof) ratio was above 3 or 2 for the SDS and CTAB system respectively. Furthermore, the systems sh ould provide high efficiency, exhibit differences in selectivity and use mo derate concentrations of modifier and surfactant, so that, if needed, furth er optimization is possible. The selected MEKC systems contained 60 mM SDS or 10 mM CTAB, respectively, in a phosphate buffer (pH 7.5) with 10% aceton itrile. Some test compounds with extreme mobilities were used to demonstrat e the suitability of the MEKC approach to detect each component of a sample . The potential of the proposed MEKC combination for impurity profiling was demonstrated by the analysis of fluvoxamine with several impurities at the 0.1% level.