Development of a Capillary Electrophoresis method for the impurity profiling of omeprazole using Quality by Design methodology

Introduction and objectives: Omeprazole (OMP) is a proton pump inhibitor that suppresses secretion of gastric acid by inhibiting the enzyme system of H+/K+ ATPase. In recent years the Analytical Quality by Design (AQbD) methodology has been widely used in analytical method development, including in capillary electrophoresis (CE), being based on process understanding and control by quality risk management. In the current study a CE method for the impurity profiling of OMP was developed, applying AQbD methodology to enhance method robustness, efficiency, and reliability. Materials and methods: The best results from the initial scouting experiments were obtained using a pseudostationary phase composed of micelles of sodium dodecyl sulfate (SDS) and n-butanol in borate buffer. A three-level screening design was used to evaluate the influence of critical method parameters on the critical method attributes, followed by a central composite orthogonal design for the method optimization. Results and discussion: Probability maps were drawn, making it possible to identify the method operable design region (MODR), that is the multivariate zone where the method requirements were fulfilled with a selected probability. The following optimized conditions were selected: 72 mM borate buffer, pH 10.0, 96 mM sodium dodecyl sulfate, 1.45 %v/v n-butanol, capillary temperature 21°C, and an applied voltage of 25 kV. Using the optimized conditions, the baseline separation of all analytes was achieved. Conclusions: The newly developed solvent-modified micellar electrokinetic chromatography (MEKC) method enables the simultaneous determination of omeprazole and 7 related substances. By following the AQbD methodology, the CE method for the impurity profiling of omeprazole could be developed in a systematic and controlled manner.