title: Quality by Design in the development of hydrophilic interaction liquid chromatography method with gradient elution for the analysis of olanzapine.
abstract: This paper deals with the development of hydrophilic interaction liquid chromatography (HILIC) method with gradient elution, in accordance with Analytical Quality by Design (AQbD) methodology, for the first time. The method is developed for olanzapine and its seven related substances. Following step by step AQbD methodology, firstly as critical process parameters (CPPs) temperature, starting content of aqueous phase and duration of linear gradient are recognized, and as critical quality attributes (CQAs) separation criterion S of critical pairs of substances are investigated. Rechtschaffen design is used for the creation of models that describe the dependence between CPPs and CQAs. The design space that is obtained at the end is used for choosing the optimal conditions (set point). The method is fully validated at the end to verify the adequacy of the chosen optimal conditions and applied to real samples.
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.
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. Electronic address: jancic.stojanovic@pharmacy.bg.ac.rs.
authors.forename: Biljana
authors.initials: B
authors.lastname: Jančić-Stojanović
authors.affiliation: University of Belgrade - Faculty of Pharmacy, Department of Physical Chemistry and Instrumental Methods, Vojvode Stepe 450, 11000, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Medenica
mesh_terms: D001569:Benzodiazepines / Q000032:analysis* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D000077152:Olanzapine
chemical_list: D001569:Benzodiazepines; D000077152:Olanzapine
keywords: AQbD; Gradient; HILIC; Impurities; Method development; Olanzapine