Stereochemical Investigation of Paroxetine: Synthesis, Characterization, and Chiral High‐Performance Liquid Chromatography Separation of All Four Stereoisomers

Abstract

The current work outlines an in‐depth methodology for synthesizing, characterizing, and chiral separation of all four stereoisomers of paroxetine hydrochloride. Paroxetine, having two stereogenic centers, was synthesized via a multi‐step reaction sequence under controlled laboratory conditions, yielding a mixture of stereoisomers, which were subsequently isolated chromatographically. The purified product was comprehensively characterized via spectroscopic techniques, including nuclear magnetic resonance ( 1 H and 13 C NMR), infrared spectroscopy, and mass spectrometry, supported by optical rotation measurements confirming the structural and stereochemical integrity of the synthesized compounds. The simultaneous isomeric resolution of paroxetine, for the first time, was achieved using high‐performance liquid chromatography equipped with a chiral stationary phase column. The technique demonstrated effective resolution of both enantiomeric and diastereomeric isomers with distinct retention times, indicating successful separation and enabling determination of isomeric purity. Overall, this study provides a comprehensive approach for the synthesis, characterization, and stereoisomeric profiling of paroxetine, thereby offering valuable implications in further impurity analysis, quality control, and regulatory assessment of chiral pharmaceutical compounds.