Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism
A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction (incuba...
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| Veröffentlicht in: | Analytical and bioanalytical chemistry 2014-01, Vol.406 (2), p.421-429 |
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| creator | Dugstad, Helene Bonkerud Petersen, Nickolaj Jacob Jensen, Henrik Gabel-Jensen, Charlotte Hansen, Steen Honoré Pedersen-Bjergaard, Stig |
| description | A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction (incubation) chamber (37 °C). The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min
−1
flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances. |
| doi_str_mv | 10.1007/s00216-013-7378-z |
| format | Article |
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−1
flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances.</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-013-7378-z</identifier><identifier>PMID: 24196121</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Amitriptyline - isolation & purification ; Amitriptyline - metabolism ; Analytical Chemistry ; Animals ; Biochemistry ; Biotransformation ; Challenges and New Directions in Analytical Sample Preparation ; Chambers ; Characterization and Evaluation of Materials ; Chemical properties ; Chemistry ; Chemistry and Materials Science ; Drugs ; Electric potential ; Electrochemical Techniques - methods ; Electrodes ; Ethers - chemistry ; Extraction ; Food Science ; Imipramine - isolation & purification ; Imipramine - metabolism ; In vitro testing ; Ionization ; Laboratory Medicine ; Male ; Mass spectrometry ; Mathematical models ; Membranes, Artificial ; Metabolism ; Metabolites ; Methods ; Microsomes, Liver - metabolism ; Monitoring/Environmental Analysis ; Power supply ; Promethazine - isolation & purification ; Promethazine - metabolism ; Rats ; Rats, Sprague-Dawley ; Research Paper ; Sample preparation ; Scientific imaging ; Solid Phase Extraction - methods ; Spectrometry, Mass, Electrospray Ionization ; Time Factors</subject><ispartof>Analytical and bioanalytical chemistry, 2014-01, Vol.406 (2), p.421-429</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><rights>COPYRIGHT 2014 Springer</rights><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c580t-ee03d2251f922c012ef1b447bfde531a2dd706eb90a92661d9778a771ae0611f3</citedby><cites>FETCH-LOGICAL-c580t-ee03d2251f922c012ef1b447bfde531a2dd706eb90a92661d9778a771ae0611f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00216-013-7378-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-013-7378-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24196121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dugstad, Helene Bonkerud</creatorcontrib><creatorcontrib>Petersen, Nickolaj Jacob</creatorcontrib><creatorcontrib>Jensen, Henrik</creatorcontrib><creatorcontrib>Gabel-Jensen, Charlotte</creatorcontrib><creatorcontrib>Hansen, Steen Honoré</creatorcontrib><creatorcontrib>Pedersen-Bjergaard, Stig</creatorcontrib><title>Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction (incubation) chamber (37 °C). The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min
−1
flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances.</description><subject>Amitriptyline - isolation & purification</subject><subject>Amitriptyline - metabolism</subject><subject>Analytical Chemistry</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biotransformation</subject><subject>Challenges and New Directions in Analytical Sample Preparation</subject><subject>Chambers</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemical properties</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Drugs</subject><subject>Electric potential</subject><subject>Electrochemical Techniques - methods</subject><subject>Electrodes</subject><subject>Ethers - chemistry</subject><subject>Extraction</subject><subject>Food Science</subject><subject>Imipramine - isolation & purification</subject><subject>Imipramine - metabolism</subject><subject>In vitro testing</subject><subject>Ionization</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mathematical models</subject><subject>Membranes, Artificial</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Methods</subject><subject>Microsomes, Liver - metabolism</subject><subject>Monitoring/Environmental Analysis</subject><subject>Power supply</subject><subject>Promethazine - isolation & purification</subject><subject>Promethazine - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research Paper</subject><subject>Sample preparation</subject><subject>Scientific imaging</subject><subject>Solid Phase Extraction - methods</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Time Factors</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNks1u1TAQhSMEoqXwAGyQJTZsUjxObMfLqvxKldjAOnKSya0rOw6209L7SrwkDrlUCAm18sKW9Z2ZM_YpipdAT4FS-TZSykCUFKpSVrIp94-KYxDQlExw-vjuXLOj4lmMV5QCb0A8LY5YDUoAg-Pi5zu8Rutnh1MiehpIf6mD7hMGs9fJ-In4kWgSnbaWoMU-Be_QdUFPSPBHWtmVmoPvkPR-mS0O5MakS-J0jCTOB0kKt2T0gQTUtkzG4e9ufrImF3J-MskHM-3WdmYi1yaLyBCWHclS3XlrontePBm1jfjisJ8U3z68_3r-qbz48vHz-dlF2fOGphKRVgNjHEbFWE-B4QhdXctuHJBXoNkwSCqwU1QrJgQMSspGSwkaqQAYq5PizVY3D_V9wZhaZ2KP1uaZ_RJbEIJSrholHoZWqubV_SivoeZUVfAAlIpKCi7k_WitqKyVEk1GX_-DXvklTPkls01JmVAV45k63aidttiaafTrH-c1oDO9n3A0-f6sakTOFSiWBbAJ-uBjDDi2czBOh9sWaLvGtN1i2uaYtmtM233WvDpYWTqHw53iTy4zwDYgzmsqMPzl9b9VfwFNePRL</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Dugstad, Helene Bonkerud</creator><creator>Petersen, Nickolaj Jacob</creator><creator>Jensen, Henrik</creator><creator>Gabel-Jensen, Charlotte</creator><creator>Hansen, Steen Honoré</creator><creator>Pedersen-Bjergaard, Stig</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature 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>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>7QH</scope><scope>7UA</scope></search><sort><creationdate>20140101</creationdate><title>Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism</title><author>Dugstad, Helene Bonkerud ; Petersen, Nickolaj Jacob ; Jensen, Henrik ; Gabel-Jensen, Charlotte ; Hansen, Steen Honoré ; Pedersen-Bjergaard, Stig</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c580t-ee03d2251f922c012ef1b447bfde531a2dd706eb90a92661d9778a771ae0611f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amitriptyline - isolation & purification</topic><topic>Amitriptyline - metabolism</topic><topic>Analytical Chemistry</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biotransformation</topic><topic>Challenges and New Directions in Analytical Sample Preparation</topic><topic>Chambers</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemical properties</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Drugs</topic><topic>Electric potential</topic><topic>Electrochemical Techniques - methods</topic><topic>Electrodes</topic><topic>Ethers - chemistry</topic><topic>Extraction</topic><topic>Food Science</topic><topic>Imipramine - isolation & purification</topic><topic>Imipramine - metabolism</topic><topic>In vitro testing</topic><topic>Ionization</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mathematical models</topic><topic>Membranes, Artificial</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Methods</topic><topic>Microsomes, Liver - 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The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min
−1
flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24196121</pmid><doi>10.1007/s00216-013-7378-z</doi><tpages>9</tpages></addata></record> |
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| ispartof | Analytical and bioanalytical chemistry, 2014-01, Vol.406 (2), p.421-429 |
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| subjects | Amitriptyline - isolation & purification Amitriptyline - metabolism Analytical Chemistry Animals Biochemistry Biotransformation Challenges and New Directions in Analytical Sample Preparation Chambers Characterization and Evaluation of Materials Chemical properties Chemistry Chemistry and Materials Science Drugs Electric potential Electrochemical Techniques - methods Electrodes Ethers - chemistry Extraction Food Science Imipramine - isolation & purification Imipramine - metabolism In vitro testing Ionization Laboratory Medicine Male Mass spectrometry Mathematical models Membranes, Artificial Metabolism Metabolites Methods Microsomes, Liver - metabolism Monitoring/Environmental Analysis Power supply Promethazine - isolation & purification Promethazine - metabolism Rats Rats, Sprague-Dawley Research Paper Sample preparation Scientific imaging Solid Phase Extraction - methods Spectrometry, Mass, Electrospray Ionization Time Factors |
| title | Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism |
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