title: Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities.
abstract: This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm × 4.6 mm, 5 μm particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 °C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.
authors: University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors: Marko
authors: M
authors: Jovanović
authors: University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia. Electronic address: tijana.rakic@pharmacy.bg.ac.rs.
authors: Tijana
authors: T
authors: Rakić
authors: University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors: Anja
authors: A
authors: Tumpa
authors: University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors: Biljana
authors: B
authors: Jančić Stojanović
mesh_terms: D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D003198:Computer Simulation; D004340:Drug Contamination; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007472:Iohexol / Q000032:analysis* / Q000592:standards; D007536:Isomerism; D008956:Models, Chemical; D015233:Models, Statistical; D009010:Monte Carlo Method; D015999:Multivariate Analysis; D011786:Quality Control; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D002021:Buffers; D007472:Iohexol
keywords: Design space; HILIC; Impurities; Iohexol; Quality by Design