An integrated Quality by Design approach towards the Design Space definition of a capillary electrophoresis method for the analysis of triptans

Analytical methods used for the determination of active pharmaceutical ingredients and drug products are an integral part of the Quality by Design (QbD) concept that is outlined in ICH Guideline Q8 for pharmaceutical development. The method used for analysis should meet its intended purpose similar to the product requirements for a clinical dosage form. The application of QbD leads to the definition of Design Space (DS), a multidimensional space which includes any combination of the variables that have been demonstrated to provide assurance of quality of the data produced by the method. In this study a capillary electrophoresis (CE) method has been developed for the separation of the seven triptans available on the market, e.g. almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan. The development was carried out by implementing each step of QbD workflow, enabling enhanced quality to be integrated into the analytical method. Control quality attributes (CQAs) were represented by resolution values of critical peak pairs and analysis time. Method scouting indicated microemulsion electrokinetic chromatography (MEEKC) as a suitable CE operative mode. In MEEKC the microemulsion droplets are regarded as the pseudostationary phase and are prepared by mixing oil, aqueous buffer and surfactant/cosurfactant in specific ratios. Mixture design is suitable for blending problems and was applied for finding the ranges for the components of the microemulsion which fulfilled the requirements for the CQAs. Risk of failure maps, obtained by means of Monte-Carlo simulations, were used for defining DS. A control strategy was established by means of system suitability tests.