An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling
This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2010-12, Vol.82 (24), p.10222-10227 |
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| creator | Fantuzzi, Andrea Capria, Ennio Mak, Lok Hang Dodhia, Vikash R Sadeghi, Sheila J Collins, Stephen Somers, Graham Huq, Ejaz Gilardi, Gianfranco |
| description | This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron. Titration experiments allowed the electrochemical measurements of K M for the four drugs, with values of 2.9, 29.1, 113.4, and 114.1 mM, respectively. The K M values are found to be in good agreement and correctly ranked with respect to the published literature on human liver microsomes and baculosomes: [ondansetron ≈ alosetron > nifedipine > quinidine]. The results presented in this paper represent a step forward for a rapid evaluation of the interaction of P450 and drug, requiring small volumes of new chemical entities to be tested. |
| doi_str_mv | 10.1021/ac102480k |
| format | Article |
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A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron. Titration experiments allowed the electrochemical measurements of K M for the four drugs, with values of 2.9, 29.1, 113.4, and 114.1 mM, respectively. The K M values are found to be in good agreement and correctly ranked with respect to the published literature on human liver microsomes and baculosomes: [ondansetron ≈ alosetron > nifedipine > quinidine]. The results presented in this paper represent a step forward for a rapid evaluation of the interaction of P450 and drug, requiring small volumes of new chemical entities to be tested.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/ac102480k</identifier><identifier>PMID: 21105702</identifier><identifier>CODEN: ANCHAM</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analytical chemistry ; Carbolines - analysis ; Cells ; Chemical reactions ; Chemistry ; Cytochrome P-450 Enzyme System - metabolism ; Drugs ; Electrochemical methods ; Electrochemical Techniques - instrumentation ; Electrochemical Techniques - methods ; Electrodes ; Exact sciences and technology ; Humans ; Liver ; Metabolism ; Microfluidics - methods ; Microsomes, Liver - metabolism ; Nifedipine - analysis ; Ondansetron - analysis ; Quinidine - analysis ; Substrate Specificity</subject><ispartof>Analytical chemistry (Washington), 2010-12, Vol.82 (24), p.10222-10227</ispartof><rights>Copyright © 2010 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Chemical Society Dec 15, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a371t-a4484ff8d91ee8f34fc40fccccdb9db843f89fdb3ec118bbb84336eb74066f5d3</citedby><cites>FETCH-LOGICAL-a371t-a4484ff8d91ee8f34fc40fccccdb9db843f89fdb3ec118bbb84336eb74066f5d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ac102480k$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ac102480k$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23739863$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21105702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fantuzzi, Andrea</creatorcontrib><creatorcontrib>Capria, Ennio</creatorcontrib><creatorcontrib>Mak, Lok Hang</creatorcontrib><creatorcontrib>Dodhia, Vikash R</creatorcontrib><creatorcontrib>Sadeghi, Sheila J</creatorcontrib><creatorcontrib>Collins, Stephen</creatorcontrib><creatorcontrib>Somers, Graham</creatorcontrib><creatorcontrib>Huq, Ejaz</creatorcontrib><creatorcontrib>Gilardi, Gianfranco</creatorcontrib><title>An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron. Titration experiments allowed the electrochemical measurements of K M for the four drugs, with values of 2.9, 29.1, 113.4, and 114.1 mM, respectively. The K M values are found to be in good agreement and correctly ranked with respect to the published literature on human liver microsomes and baculosomes: [ondansetron ≈ alosetron > nifedipine > quinidine]. The results presented in this paper represent a step forward for a rapid evaluation of the interaction of P450 and drug, requiring small volumes of new chemical entities to be tested.</description><subject>Analytical chemistry</subject><subject>Carbolines - analysis</subject><subject>Cells</subject><subject>Chemical reactions</subject><subject>Chemistry</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Drugs</subject><subject>Electrochemical methods</subject><subject>Electrochemical Techniques - instrumentation</subject><subject>Electrochemical Techniques - methods</subject><subject>Electrodes</subject><subject>Exact sciences and technology</subject><subject>Humans</subject><subject>Liver</subject><subject>Metabolism</subject><subject>Microfluidics - methods</subject><subject>Microsomes, Liver - metabolism</subject><subject>Nifedipine - analysis</subject><subject>Ondansetron - analysis</subject><subject>Quinidine - analysis</subject><subject>Substrate Specificity</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkN9LwzAQx4Mobk4f_AckCCI-VC9N1qaPY04nbDhBn0uaJjMzbTVpH_zvzdjcQO_h7jg-9-uL0DmBWwIxuRMyBMbh4wD1yTCGKOE8PkR9AKBRnAL00In3KwBCgCTHqBeHZJhC3EcvoxpPrJKta-S7qowUFs-NdI22nSmNxAsrWt24CgeHp10larxgQ8D3rlviuWpF0VjjK7wILcaaenmKjrSwXp1t4wC9PUxex9No9vz4NB7NIkFT0kaCMc605mVGlOKaMi0ZaBmsLLKy4IxqnumyoEoSwotiXaGJKlIGSaKHJR2g683cT9d8dcq3eWW8VNaKWjWdz3lM0rCJpYG8_EOums7V4bicsySLE8ZYgG42UPjde6d0_ulMJdx3TiBfq5zvVA7sxXZgV1Sq3JG_sgbgagsIHxTVTtTS-D1HU5rxhO45If3-qP8LfwBZoo9V</recordid><startdate>20101215</startdate><enddate>20101215</enddate><creator>Fantuzzi, Andrea</creator><creator>Capria, Ennio</creator><creator>Mak, Lok Hang</creator><creator>Dodhia, Vikash R</creator><creator>Sadeghi, Sheila J</creator><creator>Collins, Stephen</creator><creator>Somers, Graham</creator><creator>Huq, Ejaz</creator><creator>Gilardi, Gianfranco</creator><general>American Chemical Society</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>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>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20101215</creationdate><title>An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling</title><author>Fantuzzi, Andrea ; Capria, Ennio ; Mak, Lok Hang ; Dodhia, Vikash R ; Sadeghi, Sheila J ; Collins, Stephen ; Somers, Graham ; Huq, Ejaz ; Gilardi, Gianfranco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a371t-a4484ff8d91ee8f34fc40fccccdb9db843f89fdb3ec118bbb84336eb74066f5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analytical chemistry</topic><topic>Carbolines - analysis</topic><topic>Cells</topic><topic>Chemical reactions</topic><topic>Chemistry</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Drugs</topic><topic>Electrochemical methods</topic><topic>Electrochemical Techniques - instrumentation</topic><topic>Electrochemical Techniques - methods</topic><topic>Electrodes</topic><topic>Exact sciences and technology</topic><topic>Humans</topic><topic>Liver</topic><topic>Metabolism</topic><topic>Microfluidics - methods</topic><topic>Microsomes, Liver - metabolism</topic><topic>Nifedipine - analysis</topic><topic>Ondansetron - analysis</topic><topic>Quinidine - analysis</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fantuzzi, Andrea</creatorcontrib><creatorcontrib>Capria, Ennio</creatorcontrib><creatorcontrib>Mak, Lok Hang</creatorcontrib><creatorcontrib>Dodhia, Vikash R</creatorcontrib><creatorcontrib>Sadeghi, Sheila J</creatorcontrib><creatorcontrib>Collins, Stephen</creatorcontrib><creatorcontrib>Somers, Graham</creatorcontrib><creatorcontrib>Huq, Ejaz</creatorcontrib><creatorcontrib>Gilardi, Gianfranco</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>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fantuzzi, Andrea</au><au>Capria, Ennio</au><au>Mak, Lok Hang</au><au>Dodhia, Vikash R</au><au>Sadeghi, Sheila J</au><au>Collins, Stephen</au><au>Somers, Graham</au><au>Huq, Ejaz</au><au>Gilardi, Gianfranco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2010-12-15</date><risdate>2010</risdate><volume>82</volume><issue>24</issue><spage>10222</spage><epage>10227</epage><pages>10222-10227</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><coden>ANCHAM</coden><abstract>This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron. Titration experiments allowed the electrochemical measurements of K M for the four drugs, with values of 2.9, 29.1, 113.4, and 114.1 mM, respectively. The K M values are found to be in good agreement and correctly ranked with respect to the published literature on human liver microsomes and baculosomes: [ondansetron ≈ alosetron > nifedipine > quinidine]. The results presented in this paper represent a step forward for a rapid evaluation of the interaction of P450 and drug, requiring small volumes of new chemical entities to be tested.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>21105702</pmid><doi>10.1021/ac102480k</doi><tpages>6</tpages></addata></record> |
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| subjects | Analytical chemistry Carbolines - analysis Cells Chemical reactions Chemistry Cytochrome P-450 Enzyme System - metabolism Drugs Electrochemical methods Electrochemical Techniques - instrumentation Electrochemical Techniques - methods Electrodes Exact sciences and technology Humans Liver Metabolism Microfluidics - methods Microsomes, Liver - metabolism Nifedipine - analysis Ondansetron - analysis Quinidine - analysis Substrate Specificity |
| title | An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling |
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