Pharmaceutical Quality by Design: development of a capillary electrophoresis method for the assay of amitriptyline and its related substances

The aim of this study was to develop a selective capillary electrophoresis method for the simultaneous analysis of the tricyclic antidepressant amitriptyline (AMI) and its four main impurities, following Quality by Design (QbD) approach. The concepts of QbD, originally intended for pharmaceutical product development, can be transferred to the development of analytical separation methods, which should meet their intended purpose similarly to the product requirements for a dosage form. A SDS-based MEKC method with the addition of n-butanol as cosurfactant and acetonitrile as organic modifier was selected as operative mode, allowing a good selectivity to be obtained. Screening experimental design strategies were then applied for investigating the Knowledge Space. Critical process parameters were represented by voltage, temperature, buffer concentration and pH, concentration of cosurfactant and concentration of organic modifier. Critical quality attributes (CQAs) were represented by critical resolution values and analysis time. Design Space was finally identified by Response Surface Methodology as the multidimensional combination of variables where the probability for the different considered CQAs to be acceptable was higher than a defined quality level. The developed method was validated according to ICH guidelines and was applied to AMI tablets.