Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination

• Main Authors: Milena Rmandić (Author), Đorđe Vasilić (Author), Marija Rašević (Author), Mira Zečević (Author), Biljana Otašević (Author), Ana Protić (Author), Anđelija Malenović (Author)
• Format: Book
• Published: MDPI AG, 2023-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph16091296; 1424-8247
• Keywords: chaotropic chromatography; ziprasidone; impurities; analytical quality by design; robustness testing of method quantitative performances; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 16, Iss 9, p 1296 (2023)

In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (<i>t_{_imp. V}</i>, <i>t_{_imp. V} − t_{_imp. I}</i>, <i>S</i> and <i><W_USP></i>) was studied by Box-Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett-Burman design. <i>P_{_imp II}</i> and <i>P_{_imp V}</i> were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.