title: Identification and characterization of a new dapoxetine impurity by NMR: Transformation of N-oxide by Cope elimination.
abstract: Unknown impurity associated with the degradation process of dapoxetine base was isolated. The structure elucidation of this new compound using accurate mass data, IR and NMR spectroscopy is presented herein. The unambiguous resonance assignment concluded to the formation of geometrical isomers of cinnamyloxynaphtalenes via Cope elimination of dapoxetin-N-oxide, the major oxidative and metabolic degradation product of dapoxetine. An efficient and simple synthetic approach has also been developed for the synthesis of dapoxetine-N-oxide for the first time and cinnamyloxynaphtalene in order to confirm the proposed degradation pathway and structures of the degradation products. It was observed that the main degradation product of dapoxetine base when exposed to air is 1-(2E)-cinnamyloxynaphthalene, while its Z isomer was also confirmed as a minor impurity.
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Budapest, H-1085, Üllői út 26, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Darcsi
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Budapest H-1092, Hőgyes Endre u. 9, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Rácz
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Budapest, H-1085, Üllői út 26, Hungary. Electronic address: beni.szabolcs@pharma.semmelweis-univ.hu.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
mesh_terms: D001596:Benzylamines / Q000032:analysis* / Q000737:chemistry; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009281:Naphthalenes / Q000032:analysis* / Q000737:chemistry
chemical_list: D001596:Benzylamines; D009281:Naphthalenes; C522496:dapoxetine-N-oxide; C080598:dapoxetine
keywords: Degradation product; Drug analysis geometric (E/Z) isomer; Hofmann elimination; Impurity profiling; Metabolism; Priligy