Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography

Abstract

This paper presents multiobjective optimization of complex mixtures separation in hydrophilic interaction liquid chromatography (HILIC). The selected model mixture consisted of five psychotropic drugs: clozapine, thioridazine, sulpiride, pheniramine and lamotrigine. Three factors related to the mobile phase composition (acetonitrile content, pH of the water phase and concentration of ammonium acetate) were optimized in order to achieve the following goals: maximal separation quality, minimal total analysis duration and robustness of an optimum. The consideration of robustness in early phases of the method development provides reliable methods with low risk for failure in validation phase. The simultaneous optimization of all goals was achieved by multiple threshold approach combined with grid point search. The identified optimal separation conditions (acetonitrile content 83%, pH of the water phase 3.5 and ammonium acetate content in water phase 14 mM) were experimentally verified.