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 |
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container_title | Journal of pharmaceutical and biomedical analysis |
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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 |
format | Article |
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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.</description><identifier>ISSN: 0731-7085</identifier><identifier>EISSN: 1873-264X</identifier><identifier>DOI: 10.1016/j.jpba.2014.04.002</identifier><identifier>PMID: 24793500</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>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</subject><ispartof>Journal of pharmaceutical and biomedical analysis, 2014-08, Vol.96, p.272-277</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-2f2b2101e951474b862833dfb188eb071b22e88de4999a2519ef23c36b4638403</citedby><cites>FETCH-LOGICAL-c356t-2f2b2101e951474b862833dfb188eb071b22e88de4999a2519ef23c36b4638403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0731708514001848$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24793500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Darcsi, András</creatorcontrib><creatorcontrib>Tóth, Gergő</creatorcontrib><creatorcontrib>Kökösi, József</creatorcontrib><creatorcontrib>Béni, Szabolcs</creatorcontrib><title>Structure elucidation of a process-related impurity of dapoxetine</title><title>Journal of pharmaceutical and biomedical analysis</title><addtitle>J Pharm Biomed Anal</addtitle><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.</description><subject>Benzopyrans - chemistry</subject><subject>Benzopyrans - isolation & purification</subject><subject>Benzylamines - chemistry</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Drug Contamination</subject><subject>HPLC–DAD</subject><subject>Impurity profiling</subject><subject>Magnetic Resonance Spectroscopy - methods</subject><subject>Naphthalenes - chemistry</subject><subject>NMR</subject><subject>Priligy</subject><subject>Ring closure mechanism</subject><subject>Serotonin Uptake Inhibitors - chemistry</subject><issn>0731-7085</issn><issn>1873-264X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1LxDAQxYMo7rr6D3iQHr10nXy0TcHLIn7BggcVvIU0nUJKd1uTVNz_3pRdPQoDc5j3Hm9-hFxSWFKg-U27bIdKLxlQsYQ4wI7InMqCpywXH8dkDgWnaQEym5Ez71sAyGgpTsmMiaLkGcCcrF6DG00YHSbYjcbWOth-m_RNopPB9Qa9Tx12OmCd2M0wOht207XWQ_-NwW7xnJw0uvN4cdgL8v5w_3b3lK5fHp_vVuvU8CwPKWtYxWJtLDMqClHJnEnO66aiUmIFBa0YQylrFGVZahaLYsO44Xklci4F8AW53ufGWp8j-qA21hvsOr3FfvSKZiwvOACXUcr2UuN67x02anB2o91OUVATOtWqCZ2a0CmIAyyarg75Y7XB-s_yyyoKbvcCjF9-WXTKG4tbg7V1aIKqe_tf_g90YX54</recordid><startdate>20140805</startdate><enddate>20140805</enddate><creator>Darcsi, András</creator><creator>Tóth, Gergő</creator><creator>Kökösi, József</creator><creator>Béni, Szabolcs</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140805</creationdate><title>Structure elucidation of a process-related impurity of dapoxetine</title><author>Darcsi, András ; Tóth, Gergő ; Kökösi, József ; Béni, Szabolcs</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-2f2b2101e951474b862833dfb188eb071b22e88de4999a2519ef23c36b4638403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Benzopyrans - chemistry</topic><topic>Benzopyrans - isolation & purification</topic><topic>Benzylamines - chemistry</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Drug Contamination</topic><topic>HPLC–DAD</topic><topic>Impurity profiling</topic><topic>Magnetic Resonance Spectroscopy - methods</topic><topic>Naphthalenes - chemistry</topic><topic>NMR</topic><topic>Priligy</topic><topic>Ring closure mechanism</topic><topic>Serotonin Uptake Inhibitors - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Darcsi, András</creatorcontrib><creatorcontrib>Tóth, Gergő</creatorcontrib><creatorcontrib>Kökösi, József</creatorcontrib><creatorcontrib>Béni, Szabolcs</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Darcsi, András</au><au>Tóth, Gergő</au><au>Kökösi, József</au><au>Béni, Szabolcs</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure elucidation of a process-related impurity of dapoxetine</atitle><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle><addtitle>J Pharm Biomed Anal</addtitle><date>2014-08-05</date><risdate>2014</risdate><volume>96</volume><spage>272</spage><epage>277</epage><pages>272-277</pages><issn>0731-7085</issn><eissn>1873-264X</eissn><abstract>•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.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>24793500</pmid><doi>10.1016/j.jpba.2014.04.002</doi><tpages>6</tpages></addata></record> |
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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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