On the assessment of drug metabolism by assays of codeine and its main metabolites
Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electro...
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| Veröffentlicht in: | Therapeutic drug monitoring 2000-06, Vol.22 (3), p.258-265 |
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| creator | Haffen, E Paintaud, G Berard, M Masuyer, C Bechtel, Y Bechtel, P R |
| description | Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L(-1) for morphine and normorphine, 4 nmol/L(-1) for morphine-6-glucuronide, 3 nmol/L for the internal standard, 20 nmol/L(-1) for morphine-3-glucuronide, and 60 nmol/L(-1) for codeine and norcodeine. The coefficients of variations were |
| doi_str_mv | 10.1097/00007691-200006000-00005 |
| format | Article |
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The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L(-1) for morphine and normorphine, 4 nmol/L(-1) for morphine-6-glucuronide, 3 nmol/L for the internal standard, 20 nmol/L(-1) for morphine-3-glucuronide, and 60 nmol/L(-1) for codeine and norcodeine. The coefficients of variations were <9% for intraday and <10% for interday analyses. The recovery of codeine and its metabolites ranged from 55% (for morphine-3-glucuronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuronide). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive metabolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (MRs) of the different probe drugs were obtained (r2 > 0.95, p < 0.001). This HPLC method is simple, sensitive, accurate, and reproducible for assessing the CYP2D6 phenotype.</description><identifier>ISSN: 0163-4356</identifier><identifier>DOI: 10.1097/00007691-200006000-00005</identifier><identifier>PMID: 10850391</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Chromatography, High Pressure Liquid - methods ; Codeine - analogs & derivatives ; Codeine - urine ; Cytochrome P-450 CYP2D6 - genetics ; Cytochrome P-450 CYP2D6 - metabolism ; Debrisoquin - metabolism ; Dextromethorphan - metabolism ; Female ; Glucuronides - urine ; Humans ; Linear Models ; Male ; Methylation ; Middle Aged ; Morphine - urine ; Phenotype ; Polymorphism, Genetic ; Reproducibility of Results ; Sensitivity and Specificity</subject><ispartof>Therapeutic drug monitoring, 2000-06, Vol.22 (3), p.258-265</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-e48ad14b271e401b516858c65344b02ffa465ca455131a3513a8a461d2a01ed53</citedby><cites>FETCH-LOGICAL-c403t-e48ad14b271e401b516858c65344b02ffa465ca455131a3513a8a461d2a01ed53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10850391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haffen, E</creatorcontrib><creatorcontrib>Paintaud, G</creatorcontrib><creatorcontrib>Berard, M</creatorcontrib><creatorcontrib>Masuyer, C</creatorcontrib><creatorcontrib>Bechtel, Y</creatorcontrib><creatorcontrib>Bechtel, P R</creatorcontrib><title>On the assessment of drug metabolism by assays of codeine and its main metabolites</title><title>Therapeutic drug monitoring</title><addtitle>Ther Drug Monit</addtitle><description>Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L(-1) for morphine and normorphine, 4 nmol/L(-1) for morphine-6-glucuronide, 3 nmol/L for the internal standard, 20 nmol/L(-1) for morphine-3-glucuronide, and 60 nmol/L(-1) for codeine and norcodeine. The coefficients of variations were <9% for intraday and <10% for interday analyses. The recovery of codeine and its metabolites ranged from 55% (for morphine-3-glucuronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuronide). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive metabolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (MRs) of the different probe drugs were obtained (r2 > 0.95, p < 0.001). This HPLC method is simple, sensitive, accurate, and reproducible for assessing the CYP2D6 phenotype.</description><subject>Adult</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Codeine - analogs & derivatives</subject><subject>Codeine - urine</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Cytochrome P-450 CYP2D6 - metabolism</subject><subject>Debrisoquin - metabolism</subject><subject>Dextromethorphan - metabolism</subject><subject>Female</subject><subject>Glucuronides - urine</subject><subject>Humans</subject><subject>Linear Models</subject><subject>Male</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Morphine - urine</subject><subject>Phenotype</subject><subject>Polymorphism, Genetic</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><issn>0163-4356</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNUMtOw0AM3AOIlsIvoD1xC9jZRzZHVPGSKlVCcI42WQeC8ihxcujfk9CCsGR7NB7b0gghEW4Q0uQWpkhsilE8IztlNANzIpaAVkVaGbsQ58yfAKgdwJlYIDgDKsWleNm2cvgg6ZmJuaF2kF0pQz--y4YGn3d1xY3M97PA73keFl2gqp1W2iCrgWXjq_ZPPBBfiNPS10yXx74Sbw_3r-unaLN9fF7fbaJCgxoi0s4H1HmcIGnA3KB1xhXWKK1ziMvSa2sKr41BhV5N1buJwhB7QApGrcT14e6u775G4iFrKi6orn1L3chZgphYm9pJ6A7Cou-YeyqzXV81vt9nCNnsYfbrYfbn4Q81_7g6_hjzhsK_xYOB6hsVD21u</recordid><startdate>20000601</startdate><enddate>20000601</enddate><creator>Haffen, E</creator><creator>Paintaud, G</creator><creator>Berard, M</creator><creator>Masuyer, C</creator><creator>Bechtel, Y</creator><creator>Bechtel, P R</creator><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>20000601</creationdate><title>On the assessment of drug metabolism by assays of codeine and its main metabolites</title><author>Haffen, E ; Paintaud, G ; Berard, M ; Masuyer, C ; Bechtel, Y ; Bechtel, P R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-e48ad14b271e401b516858c65344b02ffa465ca455131a3513a8a461d2a01ed53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Codeine - analogs & derivatives</topic><topic>Codeine - urine</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Cytochrome P-450 CYP2D6 - metabolism</topic><topic>Debrisoquin - metabolism</topic><topic>Dextromethorphan - metabolism</topic><topic>Female</topic><topic>Glucuronides - urine</topic><topic>Humans</topic><topic>Linear Models</topic><topic>Male</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>Morphine - urine</topic><topic>Phenotype</topic><topic>Polymorphism, Genetic</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haffen, E</creatorcontrib><creatorcontrib>Paintaud, G</creatorcontrib><creatorcontrib>Berard, M</creatorcontrib><creatorcontrib>Masuyer, C</creatorcontrib><creatorcontrib>Bechtel, Y</creatorcontrib><creatorcontrib>Bechtel, P R</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>Therapeutic drug monitoring</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haffen, E</au><au>Paintaud, G</au><au>Berard, M</au><au>Masuyer, C</au><au>Bechtel, Y</au><au>Bechtel, P R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>On the assessment of drug metabolism by assays of codeine and its main metabolites</atitle><jtitle>Therapeutic drug monitoring</jtitle><addtitle>Ther Drug Monit</addtitle><date>2000-06-01</date><risdate>2000</risdate><volume>22</volume><issue>3</issue><spage>258</spage><epage>265</epage><pages>258-265</pages><issn>0163-4356</issn><abstract>Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L(-1) for morphine and normorphine, 4 nmol/L(-1) for morphine-6-glucuronide, 3 nmol/L for the internal standard, 20 nmol/L(-1) for morphine-3-glucuronide, and 60 nmol/L(-1) for codeine and norcodeine. The coefficients of variations were <9% for intraday and <10% for interday analyses. The recovery of codeine and its metabolites ranged from 55% (for morphine-3-glucuronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuronide). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive metabolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (MRs) of the different probe drugs were obtained (r2 > 0.95, p < 0.001). This HPLC method is simple, sensitive, accurate, and reproducible for assessing the CYP2D6 phenotype.</abstract><cop>United States</cop><pmid>10850391</pmid><doi>10.1097/00007691-200006000-00005</doi><tpages>8</tpages></addata></record> |
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| ispartof | Therapeutic drug monitoring, 2000-06, Vol.22 (3), p.258-265 |
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| subjects | Adult Chromatography, High Pressure Liquid - methods Codeine - analogs & derivatives Codeine - urine Cytochrome P-450 CYP2D6 - genetics Cytochrome P-450 CYP2D6 - metabolism Debrisoquin - metabolism Dextromethorphan - metabolism Female Glucuronides - urine Humans Linear Models Male Methylation Middle Aged Morphine - urine Phenotype Polymorphism, Genetic Reproducibility of Results Sensitivity and Specificity |
| title | On the assessment of drug metabolism by assays of codeine and its main metabolites |
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