Development of HPLC method for rapid profiling of serotonin receptor ligands and their oxidative degradants

Abstract

The serotonin receptor ligands and their related compounds are used for the treatment of central nervous system (CNS)-related disorders. The retention profile of six serotonin receptor ligands such as aripiprazole, ziprasidone, risperidone, olanzapine, mianserin, and quetiapine was investigated on two stationary phases that differ in polarities (C8 alkyl and pentafluorophenylpropyl (PFP)). The design of experiments (DoE) methodology was used to define the retention mechanism and to produce acceptable separation results. The chromatographic conditions that provide the best selectivity characteristics are considered for the separation of structurally related oxidative impurities. The selected conditions (C8 stationary phase, 40% acetonitrile, 20mM ammonium acetate, 25 ℃) showed better sensitivity and improved selectivity in the separation of aripiprazole, ziprasidone, and their oxidative degradants compared to the already developed high-performance liquid chromatography methods. The selected method was validated for the determination of aripiprazole in pharmaceutical forms and was found to be selective, sensitive, precise, accurate, and robust. It can be used as a basis for rapid chromatographic profiling of serotonin receptor ligands and their related impurities.