Determination of enantiomeric purity of esomeprazole by capillary electrophoresis

Abstract

Abstract Proton pump inhibitors are the most effective agents used in gastric hyper-acidity-related disorders. Omeprazole is a benzimidazole-derivative compound with an asymmetric sulphur in its structure, which generates its chiral character. Esomeprazole (S-omeprazole) was the first proton pump inhibitor introduced as an enantiomerically pure compound in therapy, after the successful chiral switch of the racemic omeprazole. This work is aimed at performing a complementary study to an already published chiral separation method of omeprazole. As preliminary analysis, the electrophoretic behavior of omeprazole enantiomers and the possible mechanism of the chiral resolution was studied using different background electrolytes containing different β-cyclodextrin derivatives, as chiral selectors. The robustness of the chiral separation method was tested by applying a Plackett-Burman design. The method was validated according to current ICH guidelines and proved to be reliable, linear, precise and accurate for the determination of 0.2% R-omeprazole as chiral impurity in esomeprazole samples. The validated method was successfully used for the analysis of esomeprazole-containing gastro-resistant tablets. According to our results, valuable information on the mechanism of chiral separation of omeprazole was gained and the application area of the previously developed method was successfully enlarged. The presented rapid and cost-effective capillary electrophoresis method proved to be suitable for the determination of enantiomeric purity of esomeprazole from pharmaceutical preparations and could represent an alternative for the available compendial methods.