title: Chromatographic analysis of olopatadine in hydrophilic interaction liquid chromatography.
abstract: In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.
authors.affiliation: Department of Drug Control and Examination, Sector for Pharmacy, Military Medical Academy, Crnotravska 17, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Maksić
authors.affiliation: Department of Drug Analysis, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11000, Serbia.
authors.forename: Marko
authors.initials: M
authors.lastname: Jovanović
authors.affiliation: Department of Drug Analysis, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11000, Serbia.
authors.forename: Tijana
authors.initials: T
authors.lastname: Rakić
authors.affiliation: Medicines and Medical Devices Agency of Serbia, Vojvode Stepe 458, Belgrade, Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Popović
authors.affiliation: Department of Drug Analysis, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11000, Serbia.
authors.forename: Darko
authors.initials: D
authors.lastname: Ivanović
authors.affiliation: Department of Drug Analysis, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11000, Serbia jancic.stojanovic@pharmacy.bg.ac.rs.
authors.forename: Biljana
authors.initials: B
authors.lastname: Jančić-Stojanović
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D003990:Dibenzoxepins / Q000737:chemistry* / Q000302:isolation & purification; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D015394:Molecular Structure; D000069605:Olopatadine Hydrochloride
chemical_list: D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride