Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism
1. In vitro metabolism of the anticholinergic drug, cimetropium bromide, was investigated using four different animal hepatic microsomal incubates derived from rat, hamster, guinea pig, and mouse livers. 2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N...
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| Veröffentlicht in: | Xenobiotica 1992, Vol.22 (6), p.641-655 |
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| creator | Kajbaf, M. Jahanshahi, M. Lamb, J. H. Gorrod, J. W. Naylor, S. |
| description | 1. In vitro metabolism of the anticholinergic drug, cimetropium bromide, was investigated using four different animal hepatic microsomal incubates derived from rat, hamster, guinea pig, and mouse livers.
2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N-methylenecyclopropyl-scopine functionality by monitoring loss of 54 daltons (corresponding to loss of methylenecyclopropane) in microsomal incubates.
3. A CNL loss of 46 daltons was used to screen for the presence of ester hydrolysis products.
4. A comparison of the daughter ion spectra obtained on ions detected by CNL scanning, with daughter ion spectra of synthetic standards, determined the presence of ten metabolites of cimetropium bromide.
5. Hydroxylation of the aromatic ring in the ester side-chain was found to be the major metabolic pathway, and ester bond hydrolysis was a minor metabolic pathway.
6. N-Demethylation of the bridgehead nitrogen was observed only in rat and hamster incubates.
7. Using the method of CNL scanning it was possible to screen different animal microsomal incubates without resorting to any major purification procedures such as h.p.l.c.
8. This scanning method revealed differences between species in the metabolic pathways of cimetropium bromide. |
| doi_str_mv | 10.3109/00498259209053127 |
| format | Article |
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2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N-methylenecyclopropyl-scopine functionality by monitoring loss of 54 daltons (corresponding to loss of methylenecyclopropane) in microsomal incubates.
3. A CNL loss of 46 daltons was used to screen for the presence of ester hydrolysis products.
4. A comparison of the daughter ion spectra obtained on ions detected by CNL scanning, with daughter ion spectra of synthetic standards, determined the presence of ten metabolites of cimetropium bromide.
5. Hydroxylation of the aromatic ring in the ester side-chain was found to be the major metabolic pathway, and ester bond hydrolysis was a minor metabolic pathway.
6. N-Demethylation of the bridgehead nitrogen was observed only in rat and hamster incubates.
7. Using the method of CNL scanning it was possible to screen different animal microsomal incubates without resorting to any major purification procedures such as h.p.l.c.
8. This scanning method revealed differences between species in the metabolic pathways of cimetropium bromide.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.3109/00498259209053127</identifier><identifier>PMID: 1441588</identifier><identifier>CODEN: XENOBH</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Animals ; Biological and medical sciences ; Cholinergic system ; Cricetinae ; Guinea Pigs ; In Vitro Techniques ; Male ; Mass Spectrometry ; Medical sciences ; Mesocricetus ; Mice ; Microsomes, Liver - metabolism ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Parasympatholytics - metabolism ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; Scopolamine Derivatives - metabolism ; Species Specificity</subject><ispartof>Xenobiotica, 1992, Vol.22 (6), p.641-655</ispartof><rights>1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1992</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-8852357213115facc0b7375428e76df5b3614fbeceac21957afed37ce745527d3</citedby><cites>FETCH-LOGICAL-c442t-8852357213115facc0b7375428e76df5b3614fbeceac21957afed37ce745527d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/00498259209053127$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/00498259209053127$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4309131$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1441588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kajbaf, M.</creatorcontrib><creatorcontrib>Jahanshahi, M.</creatorcontrib><creatorcontrib>Lamb, J. H.</creatorcontrib><creatorcontrib>Gorrod, J. W.</creatorcontrib><creatorcontrib>Naylor, S.</creatorcontrib><title>Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. In vitro metabolism of the anticholinergic drug, cimetropium bromide, was investigated using four different animal hepatic microsomal incubates derived from rat, hamster, guinea pig, and mouse livers.
2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N-methylenecyclopropyl-scopine functionality by monitoring loss of 54 daltons (corresponding to loss of methylenecyclopropane) in microsomal incubates.
3. A CNL loss of 46 daltons was used to screen for the presence of ester hydrolysis products.
4. A comparison of the daughter ion spectra obtained on ions detected by CNL scanning, with daughter ion spectra of synthetic standards, determined the presence of ten metabolites of cimetropium bromide.
5. Hydroxylation of the aromatic ring in the ester side-chain was found to be the major metabolic pathway, and ester bond hydrolysis was a minor metabolic pathway.
6. N-Demethylation of the bridgehead nitrogen was observed only in rat and hamster incubates.
7. Using the method of CNL scanning it was possible to screen different animal microsomal incubates without resorting to any major purification procedures such as h.p.l.c.
8. This scanning method revealed differences between species in the metabolic pathways of cimetropium bromide.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cholinergic system</subject><subject>Cricetinae</subject><subject>Guinea Pigs</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Mesocricetus</subject><subject>Mice</subject><subject>Microsomes, Liver - metabolism</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Parasympatholytics - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Scopolamine Derivatives - metabolism</subject><subject>Species Specificity</subject><issn>0049-8254</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUsuK1TAYDqKMx9EHcCFkIe6quTYtutHBGwy40XVJkz9zMrRJTVLlPJTvaOo5OogwrvLz3XL5gtBjSp5zSvoXhIi-Y7JnpCeSU6buoB3lbdtUqLuLdhvfVIG4jx7kfE0IaSljZ-iMCkFl1-3Qjzc-6qCnQ_FGT1gvy1SH4mPIODpcdLAw41nnjPMCpqQ4Q0kH7AMue9iWb76CuKJ6jJPP8y9bpXSokfsKBUhX3mCb1its_GaPi19nPNYsbwGXiC2Umo2tdw4SBAN5S9429HW8yX6I7jk9ZXh0Ws_Rl3dvP198aC4_vf948fqyMUKw0nSdZFwqRjml0mljyKi4koJ1oFrr5MhbKtwIBrRhtJdKO7BcGVBCSqYsP0fPjrlLil9XyGWYfTYwTTpAXPOgOGdMCP5fIW2V4L1gVUiPQpNizgncsCQ_63QYKBm2Lod_uqyeJ6fwdZzB3jiO5VX-6YnXuZbnkg7G5z8ywUlfX6DKXh1lPriYZv09pskORR-mmH57-G2nePmXfQ96KnujEwzXcU317-Rb7vAT-cLP9A</recordid><startdate>1992</startdate><enddate>1992</enddate><creator>Kajbaf, M.</creator><creator>Jahanshahi, M.</creator><creator>Lamb, J. H.</creator><creator>Gorrod, J. W.</creator><creator>Naylor, S.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>1992</creationdate><title>Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism</title><author>Kajbaf, M. ; Jahanshahi, M. ; Lamb, J. H. ; Gorrod, J. W. ; Naylor, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-8852357213115facc0b7375428e76df5b3614fbeceac21957afed37ce745527d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cholinergic system</topic><topic>Cricetinae</topic><topic>Guinea Pigs</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Mesocricetus</topic><topic>Mice</topic><topic>Microsomes, Liver - metabolism</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Parasympatholytics - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Scopolamine Derivatives - metabolism</topic><topic>Species Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kajbaf, M.</creatorcontrib><creatorcontrib>Jahanshahi, M.</creatorcontrib><creatorcontrib>Lamb, J. H.</creatorcontrib><creatorcontrib>Gorrod, J. W.</creatorcontrib><creatorcontrib>Naylor, S.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kajbaf, M.</au><au>Jahanshahi, M.</au><au>Lamb, J. H.</au><au>Gorrod, J. W.</au><au>Naylor, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>1992</date><risdate>1992</risdate><volume>22</volume><issue>6</issue><spage>641</spage><epage>655</epage><pages>641-655</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><coden>XENOBH</coden><abstract>1. In vitro metabolism of the anticholinergic drug, cimetropium bromide, was investigated using four different animal hepatic microsomal incubates derived from rat, hamster, guinea pig, and mouse livers.
2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N-methylenecyclopropyl-scopine functionality by monitoring loss of 54 daltons (corresponding to loss of methylenecyclopropane) in microsomal incubates.
3. A CNL loss of 46 daltons was used to screen for the presence of ester hydrolysis products.
4. A comparison of the daughter ion spectra obtained on ions detected by CNL scanning, with daughter ion spectra of synthetic standards, determined the presence of ten metabolites of cimetropium bromide.
5. Hydroxylation of the aromatic ring in the ester side-chain was found to be the major metabolic pathway, and ester bond hydrolysis was a minor metabolic pathway.
6. N-Demethylation of the bridgehead nitrogen was observed only in rat and hamster incubates.
7. Using the method of CNL scanning it was possible to screen different animal microsomal incubates without resorting to any major purification procedures such as h.p.l.c.
8. This scanning method revealed differences between species in the metabolic pathways of cimetropium bromide.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>1441588</pmid><doi>10.3109/00498259209053127</doi><tpages>15</tpages></addata></record> |
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| ispartof | Xenobiotica, 1992, Vol.22 (6), p.641-655 |
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| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Access via Taylor & Francis |
| subjects | Animals Biological and medical sciences Cholinergic system Cricetinae Guinea Pigs In Vitro Techniques Male Mass Spectrometry Medical sciences Mesocricetus Mice Microsomes, Liver - metabolism Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Parasympatholytics - metabolism Pharmacology. Drug treatments Rats Rats, Wistar Scopolamine Derivatives - metabolism Species Specificity |
| title | Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism |
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