Structure elucidation of a process-related impurity of dapoxetine

•A novel dapoxetine by-product has been identified using NMR and MS.•The mechanism for the impurity formation was proposed and also confirmed by synthesis.•The separation of dapoxetine and the process-related impurities was accomplished by HPLC. Unknown by-product associated with the synthesis of da...

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Veröffentlicht in:Journal of pharmaceutical and biomedical analysis 2014-08, Vol.96, p.272-277
Hauptverfasser: Darcsi, András, Tóth, Gergő, Kökösi, József, Béni, Szabolcs
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container_end_page 277
container_issue
container_start_page 272
container_title Journal of pharmaceutical and biomedical analysis
container_volume 96
creator Darcsi, András
Tóth, Gergő
Kökösi, József
Béni, Szabolcs
description •A novel dapoxetine by-product has been identified using NMR and MS.•The mechanism for the impurity formation was proposed and also confirmed by synthesis.•The separation of dapoxetine and the process-related impurities was accomplished by HPLC. Unknown by-product associated with the synthesis of dapoxetine was isolated. The structure elucidation of this new compound using accurate mass data and NMR spectroscopy is presented herein. The unambiguous resonance assignment concluded to the formation of a tricyclic compound 4-phenyl-2H,3H,4H-naphtho[1,2-b]pyran, a new impurity of dapoxetine which has never been reported previously. A proposed mechanism for the formation of the new carbon–carbon bond is discussed. For the separation of dapoxetine and the process-related impurities, a gradient HPLC method was developed.
doi_str_mv 10.1016/j.jpba.2014.04.002
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Benzopyrans - chemistry
Benzopyrans - isolation & purification
Benzylamines - chemistry
Chromatography, High Pressure Liquid - methods
Drug Contamination
HPLC–DAD
Impurity profiling
Magnetic Resonance Spectroscopy - methods
Naphthalenes - chemistry
NMR
Priligy
Ring closure mechanism
Serotonin Uptake Inhibitors - chemistry
title Structure elucidation of a process-related impurity of dapoxetine
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