Simultaneous enantio- and diastereo-selective high-performance liquid chromatography separation of paroxetine on an immobilized amylose-based chiral stationary phase under green reversed-phase conditions.

• Paroxetine displays two stereogenic centers but only the (3 S ,4 R) stereoisomer is clinically useful. • A direct method was developed for resolving the four stereoisomers in a single HPLC run. • Amylose tris(3,5-dimethylphenylcarbamate)-based CSP was used as a chiral chromatographic support. • A mobile phase consisting of ethanol-water-diethylamine 80:20:0.1 was employed. • The enantiomeric separation did not suffer from the presence of other chiral and achiral impurities. A simple and green high-performance liquid chromatography method for the separation of paroxetine from its enantiomeric and diastereomeric impurities has been developed. The simultaneous chromatographic resolution was carried out on the amylose-based Chiralpak IA-3 chiral stationary phase using the mixture ethanol-water-diethylamine 80:20:0.1 (v/v/v) as a mobile phase. The effects of substitution of ethanol with methanol or acetonitrile and changes in column temperature on selectivity have been carefully investigated. The optimized single-run HPLC protocol allows the baseline separation of the enantiomers of paroxetine without suffering from interference from five other chiral and achiral impurities reported in the monograph of the European Pharmacopoeia. [ABSTRACT FROM AUTHOR]