title: Application of Analytical Quality by Design concept for bilastine and its degradation impurities determination by hydrophilic interaction liquid chromatographic method.
abstract: This paper deals with the development of hydrophilic interaction liquid chromatographic (HILIC) method for the analysis of bilastine and its degradation impurities following Analytical Quality by Design approach. It is the first time that the method for bilastine and its impurities is proposed. The main objective was to identify the conditions where an adequate separation in minimal analysis duration could be achieved within a robust region. Critical process parameters which have the most influence on method performance were defined as acetonitrile content in the mobile phase, pH of the aqueous phase and ammonium acetate concentration in the aqueous phase. Box-Behnken design was applied for establishing a relationship between critical process parameters and critical quality attributes. The defined mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing and the method is validated to verify the adequacy of selected optimal conditions: the analytical column Luna(®) HILIC (100mm×4.6mm, 5μm particle size); mobile phase consisted of acetonitrile-aqueous phase (50mM ammonium acetate, pH adjusted to 5.3 with glacial acetic acid) (90.5:9.5, v/v); column temperature 30°C, mobile phase flow rate 1mLmin(-1), wavelength of detection 275nm.
authors.affiliation: Medicines and Medical Devices Agency of Serbia, Vojvode Stepe 458, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Terzić
authors.affiliation: Medicines and Medical Devices Agency of Serbia, Vojvode Stepe 458, 11000 Belgrade, Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Popović
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Stajić
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Anja
authors.initials: A
authors.lastname: Tumpa
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia. Electronic address: jancic.stojanovic@pharmacy.bg.ac.rs.
authors.forename: Biljana
authors.initials: B
authors.lastname: Jančić-Stojanović
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D010880:Piperidines / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D010880:Piperidines; C445659:bilastine
keywords: Analytical Quality by Design; Analytical method development; Bilastine; Degradation impurities; Design space; HILIC