title: Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles.
abstract: The aim of this paper is to present a development of liquid chromatographic method when chaotropic salts are used as mobile phase additives following the QbD principles. The effect of critical process parameters (column chemistry, salt nature and concentration, acetonitrile content and column temperature) on the critical quality attributes (retention of the first and last eluting peak and separation of the critical peak pairs) was studied applying the design of experiments-design space methodology (DoE-DS). D-optimal design is chosen in order to simultaneously examine both categorical and numerical factors in minimal number of experiments. Two ways for the achievement of quality assurance were performed and compared. Namely, the uncertainty originating from the models was assessed by Monte Carlo simulations propagating the error equal to the variance of the model residuals and propagating the error originating from the model coefficients' calculation. The baseline separation of pramipexole and its five impurities is achieved fulfilling all the required criteria while the method validation proved its reliability.
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Vemić
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Tijana
authors.initials: T
authors.lastname: Rakić
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, Belgrade, Serbia. Electronic address: andja@pharmacy.bg.ac.rs.
authors.forename: Anđelija
authors.initials: A
authors.lastname: Malenović
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Physical Chemistry and Instrumental Methods, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Medenica
mesh_terms: D052160:Benzothiazoles / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D009010:Monte Carlo Method; D000077487:Pramipexole
chemical_list: D052160:Benzothiazoles; D000077487:Pramipexole
keywords: Chaotropic salts; Design space; Liquid chromatography; Pramipexole; Quality-by-design