Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat
RGH-1756, 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4- 14C}-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile,...
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| Veröffentlicht in: | Journal of pharmaceutical and biomedical analysis 2001-03, Vol.24 (5), p.877-885 |
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| creator | GEMESI, L. I KAPAS, M SZEBERENYI, Sz |
| description | RGH-1756, 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4-
14C}-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with
14C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed. Good separation of the compounds has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column. Radiometry and mass spectrometry have been applied to detect and characterise the metabolites. The metabolite formed by oxidative cleavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as one of the main metabolites excreted in the bile where the unchanged compound has not been detected. |
| doi_str_mv | 10.1016/S0731-7085(00)00556-2 |
| format | Article |
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14C}-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with
14C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed. Good separation of the compounds has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column. Radiometry and mass spectrometry have been applied to detect and characterise the metabolites. The metabolite formed by oxidative cleavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as one of the main metabolites excreted in the bile where the unchanged compound has not been detected.</description><identifier>ISSN: 0731-7085</identifier><identifier>EISSN: 1873-264X</identifier><identifier>DOI: 10.1016/S0731-7085(00)00556-2</identifier><identifier>PMID: 11248481</identifier><identifier>CODEN: JPBADA</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol [2,1-b]thiazolyl)-phenoxy]-butyl-4- 14C}-piperazine ; Analysis ; Animals ; Antipsychotic ; Bile - metabolism ; Biological and medical sciences ; Chromatography, High Pressure Liquid - methods ; Dopamine Antagonists - blood ; Dopamine Antagonists - metabolism ; Dopamine Antagonists - pharmacokinetics ; Dopamine D2 Receptor Antagonists ; Feces - chemistry ; General pharmacology ; In vitro and in vivo metabolism ; In Vitro Techniques ; LC-MS ; Male ; Mass Spectrometry - methods ; Medical sciences ; Pharmacology. Drug treatments ; Piperazines - metabolism ; Piperazines - pharmacokinetics ; Radiometry ; Rat ; Rats ; Rats, Wistar ; Receptors, Dopamine D3 ; RGH-1756 ; Thiazoles - metabolism ; Thiazoles - pharmacokinetics ; Turboionspray</subject><ispartof>Journal of pharmaceutical and biomedical analysis, 2001-03, Vol.24 (5), p.877-885</ispartof><rights>2001 Elsevier Science B.V.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-4c7516c73fb0bcf4eb0e2839841bfba2388cd59044e2cec7b8301675c545a0983</citedby><cites>FETCH-LOGICAL-c389t-4c7516c73fb0bcf4eb0e2839841bfba2388cd59044e2cec7b8301675c545a0983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0731-7085(00)00556-2$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,777,781,786,787,3537,23911,23912,25121,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=963170$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11248481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GEMESI, L. I</creatorcontrib><creatorcontrib>KAPAS, M</creatorcontrib><creatorcontrib>SZEBERENYI, Sz</creatorcontrib><title>Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat</title><title>Journal of pharmaceutical and biomedical analysis</title><addtitle>J Pharm Biomed Anal</addtitle><description>RGH-1756, 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4-
14C}-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with
14C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed. Good separation of the compounds has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column. Radiometry and mass spectrometry have been applied to detect and characterise the metabolites. The metabolite formed by oxidative cleavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as one of the main metabolites excreted in the bile where the unchanged compound has not been detected.</description><subject>1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol [2,1-b]thiazolyl)-phenoxy]-butyl-4- 14C}-piperazine</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antipsychotic</subject><subject>Bile - metabolism</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Dopamine Antagonists - blood</subject><subject>Dopamine Antagonists - metabolism</subject><subject>Dopamine Antagonists - pharmacokinetics</subject><subject>Dopamine D2 Receptor Antagonists</subject><subject>Feces - chemistry</subject><subject>General pharmacology</subject><subject>In vitro and in vivo metabolism</subject><subject>In Vitro Techniques</subject><subject>LC-MS</subject><subject>Male</subject><subject>Mass Spectrometry - methods</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - metabolism</subject><subject>Piperazines - pharmacokinetics</subject><subject>Radiometry</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Dopamine D3</subject><subject>RGH-1756</subject><subject>Thiazoles - metabolism</subject><subject>Thiazoles - pharmacokinetics</subject><subject>Turboionspray</subject><issn>0731-7085</issn><issn>1873-264X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0NFqFDEUBuAgil1bH0EJCGIvpk0mySRzVcpiW2FFsArehcyZMzQyO1mT7ELBh2-mu6yXXoUTvj85_IS84-yCM95c3jMteKWZUZ8YO2dMqaaqX5AFN1pUdSN_vSSLIzkhb1L6zYrirXxNTjivpZGGL8jf681m9OCyDxMNA10tq6_31E1ufEw-0RxofkAKDy46yBh9Osr53k9053MMJdDvh12ga8yuC6PPSDcxDH7ENPvvt3cV16qZ3ZyNLp-RV4MbE749nKfk583nH8u7avXt9svyelWBMG2uJGjFG9Bi6FgHg8SOYW1EayTvhs7VwhjoVcukxBoQdGdEaUgrUFI51hpxSj7u3y37_NliynbtE-A4ugnDNlndtJppzQtUewgxpBRxsJvo1y4-Ws7sXLt9rt3OnVrG7HPtti6594cPtt0a-3-pQ88FfDgAl8CNQ3QT-HR0bSO4ZkVd7RWWMnYeo03gcQLsfUTItg_-P4s8AZNKnaQ</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>GEMESI, L. I</creator><creator>KAPAS, M</creator><creator>SZEBERENYI, Sz</creator><general>Elsevier B.V</general><general>Elsevier Science</general><scope>IQODW</scope><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>20010301</creationdate><title>Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat</title><author>GEMESI, L. I ; KAPAS, M ; SZEBERENYI, Sz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-4c7516c73fb0bcf4eb0e2839841bfba2388cd59044e2cec7b8301675c545a0983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol [2,1-b]thiazolyl)-phenoxy]-butyl-4- 14C}-piperazine</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antipsychotic</topic><topic>Bile - metabolism</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Dopamine Antagonists - blood</topic><topic>Dopamine Antagonists - metabolism</topic><topic>Dopamine Antagonists - pharmacokinetics</topic><topic>Dopamine D2 Receptor Antagonists</topic><topic>Feces - chemistry</topic><topic>General pharmacology</topic><topic>In vitro and in vivo metabolism</topic><topic>In Vitro Techniques</topic><topic>LC-MS</topic><topic>Male</topic><topic>Mass Spectrometry - methods</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazines - metabolism</topic><topic>Piperazines - pharmacokinetics</topic><topic>Radiometry</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Dopamine D3</topic><topic>RGH-1756</topic><topic>Thiazoles - metabolism</topic><topic>Thiazoles - pharmacokinetics</topic><topic>Turboionspray</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GEMESI, L. I</creatorcontrib><creatorcontrib>KAPAS, M</creatorcontrib><creatorcontrib>SZEBERENYI, Sz</creatorcontrib><collection>Pascal-Francis</collection><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>GEMESI, L. I</au><au>KAPAS, M</au><au>SZEBERENYI, Sz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat</atitle><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle><addtitle>J Pharm Biomed Anal</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>24</volume><issue>5</issue><spage>877</spage><epage>885</epage><pages>877-885</pages><issn>0731-7085</issn><eissn>1873-264X</eissn><coden>JPBADA</coden><abstract>RGH-1756, 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4-
14C}-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with
14C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed. Good separation of the compounds has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column. Radiometry and mass spectrometry have been applied to detect and characterise the metabolites. The metabolite formed by oxidative cleavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as one of the main metabolites excreted in the bile where the unchanged compound has not been detected.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>11248481</pmid><doi>10.1016/S0731-7085(00)00556-2</doi><tpages>9</tpages></addata></record> |
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| subjects | 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol [2,1-b]thiazolyl)-phenoxy]-butyl-4- 14C}-piperazine Analysis Animals Antipsychotic Bile - metabolism Biological and medical sciences Chromatography, High Pressure Liquid - methods Dopamine Antagonists - blood Dopamine Antagonists - metabolism Dopamine Antagonists - pharmacokinetics Dopamine D2 Receptor Antagonists Feces - chemistry General pharmacology In vitro and in vivo metabolism In Vitro Techniques LC-MS Male Mass Spectrometry - methods Medical sciences Pharmacology. Drug treatments Piperazines - metabolism Piperazines - pharmacokinetics Radiometry Rat Rats Rats, Wistar Receptors, Dopamine D3 RGH-1756 Thiazoles - metabolism Thiazoles - pharmacokinetics Turboionspray |
| title | Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat |
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