Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS)
A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine, N- des-methylatomoxetine, and 4-hydroxyatomoxetine- O-glucuronide) has been developed for human plasma and urine. Using stable-la...
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Veröffentlicht in: | Journal of pharmaceutical and biomedical analysis 2005-07, Vol.38 (4), p.720-733 |
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container_title | Journal of pharmaceutical and biomedical analysis |
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creator | Mullen, John H. Shugert, Richard L. Ponsler, George D. Li, Qimin Sundaram, Bhaskar Coales, Heather L. Yakupkovic, Joseph E. LeLacheur, Richard M. Wheeler, William J. Belas, Frank J. Sauer, John-Michael |
description | A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine,
N-
des-methylatomoxetine, and 4-hydroxyatomoxetine-
O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate and precise for the analytes in all species, resulting in inter-batch accuracy (percent relative error, %RE) within 100
±
13% and inter-batch precision (relative standard deviation, %RSD) within 11%. Stability was demonstrated for the analytes in neat solutions and the reconstitution solvent, as well as plasma and urine (with or without the deconjugation reagent). The method was simple, robust (utilized for the analysis of several hundred clinical study samples), and amenable to high sample throughput. |
doi_str_mv | 10.1016/j.jpba.2005.02.007 |
format | Article |
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N-
des-methylatomoxetine, and 4-hydroxyatomoxetine-
O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate and precise for the analytes in all species, resulting in inter-batch accuracy (percent relative error, %RE) within 100
±
13% and inter-batch precision (relative standard deviation, %RSD) within 11%. Stability was demonstrated for the analytes in neat solutions and the reconstitution solvent, as well as plasma and urine (with or without the deconjugation reagent). The method was simple, robust (utilized for the analysis of several hundred clinical study samples), and amenable to high sample throughput.</description><identifier>ISSN: 0731-7085</identifier><identifier>EISSN: 1873-264X</identifier><identifier>DOI: 10.1016/j.jpba.2005.02.007</identifier><identifier>PMID: 15967301</identifier><identifier>CODEN: JPBADA</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>ADHD ; Analysis ; Analytical, structural and metabolic biochemistry ; Atomoxetine Hydrochloride ; Bioanalytical ; Biological and medical sciences ; Biotransformation ; Calibration ; Chromatography ; Chromatography, Liquid ; Clinical ; Fundamental and applied biological sciences. Psychology ; General pharmacology ; Glucuronides - blood ; Glucuronides - urine ; Humans ; Mass Spectrometry ; Medical sciences ; Oxidation-Reduction ; Pharmacology. Drug treatments ; Propylamines - analysis ; Propylamines - blood ; Propylamines - urine ; Quantification ; Reference Standards ; Reproducibility of Results ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Straterra</subject><ispartof>Journal of pharmaceutical and biomedical analysis, 2005-07, Vol.38 (4), p.720-733</ispartof><rights>2005 Elsevier B.V.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-b90db9b87e5c35a5ceb1e9ceef6bd94f0cac07d989fa20caf1604f71a6bb61313</citedby><cites>FETCH-LOGICAL-c384t-b90db9b87e5c35a5ceb1e9ceef6bd94f0cac07d989fa20caf1604f71a6bb61313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpba.2005.02.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16903846$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15967301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mullen, John H.</creatorcontrib><creatorcontrib>Shugert, Richard L.</creatorcontrib><creatorcontrib>Ponsler, George D.</creatorcontrib><creatorcontrib>Li, Qimin</creatorcontrib><creatorcontrib>Sundaram, Bhaskar</creatorcontrib><creatorcontrib>Coales, Heather L.</creatorcontrib><creatorcontrib>Yakupkovic, Joseph E.</creatorcontrib><creatorcontrib>LeLacheur, Richard M.</creatorcontrib><creatorcontrib>Wheeler, William J.</creatorcontrib><creatorcontrib>Belas, Frank J.</creatorcontrib><creatorcontrib>Sauer, John-Michael</creatorcontrib><title>Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS)</title><title>Journal of pharmaceutical and biomedical analysis</title><addtitle>J Pharm Biomed Anal</addtitle><description>A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine,
N-
des-methylatomoxetine, and 4-hydroxyatomoxetine-
O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate and precise for the analytes in all species, resulting in inter-batch accuracy (percent relative error, %RE) within 100
±
13% and inter-batch precision (relative standard deviation, %RSD) within 11%. Stability was demonstrated for the analytes in neat solutions and the reconstitution solvent, as well as plasma and urine (with or without the deconjugation reagent). The method was simple, robust (utilized for the analysis of several hundred clinical study samples), and amenable to high sample throughput.</description><subject>ADHD</subject><subject>Analysis</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Atomoxetine Hydrochloride</subject><subject>Bioanalytical</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Calibration</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Clinical</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General pharmacology</subject><subject>Glucuronides - blood</subject><subject>Glucuronides - urine</subject><subject>Humans</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Oxidation-Reduction</subject><subject>Pharmacology. Drug treatments</subject><subject>Propylamines - analysis</subject><subject>Propylamines - blood</subject><subject>Propylamines - urine</subject><subject>Quantification</subject><subject>Reference Standards</subject><subject>Reproducibility of Results</subject><subject>Spectrometry, Fluorescence</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>Straterra</subject><issn>0731-7085</issn><issn>1873-264X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuKFDEUhgtRnHb0BVxINoouqiepe8FspPEGLbMYBXfhVHKqO00lqc5lnHk-X8y0XTA7IXAI-f5zTv4_y14zumaUNVeH9WEeYF1QWq9psaa0fZKtWNeWedFUv55mK9qWLG9pV19kL7w_0ASyvnqeXbC6b9qSslX251bpOAUwaKMnxwgmqFEJCMoaYkcCwWp7j0EZJODJb5ymU1XBk9kpDe6B2HslE3-XACPJTb6boojOGiWRaAww2EkFTBpD9lGDIfMEXsM_OrpT4-iV2ZFJHaOSROyd1WnszsG8fyBpNYmaaPCe-BlFSK8Y0tj3283V99t0PrzMno0weXy11Mvs5-dPPzZf8-3Nl2-bj9tclF0V8qGncuiHrsValDXUAgeGvUAcm0H21UgFCNrKvutHKNJlZA2txpZBMwwNK1l5mb07952dPUb0gWvlRXLk7B5v2r6uaEkTWJxB4az3Dke-eMUZ5afo-IGfouOn6DgteIouid4s3eOgUT5KlqwS8HYBwAuYRgdGKP_INT1N_2wSd33mMHlxp9BxLxQagVK55B-XVv1vj789KL28</recordid><startdate>20050715</startdate><enddate>20050715</enddate><creator>Mullen, John H.</creator><creator>Shugert, Richard L.</creator><creator>Ponsler, George D.</creator><creator>Li, Qimin</creator><creator>Sundaram, Bhaskar</creator><creator>Coales, Heather L.</creator><creator>Yakupkovic, Joseph E.</creator><creator>LeLacheur, Richard M.</creator><creator>Wheeler, William J.</creator><creator>Belas, Frank J.</creator><creator>Sauer, John-Michael</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>20050715</creationdate><title>Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS)</title><author>Mullen, John H. ; Shugert, Richard L. ; Ponsler, George D. ; Li, Qimin ; Sundaram, Bhaskar ; Coales, Heather L. ; Yakupkovic, Joseph E. ; LeLacheur, Richard M. ; Wheeler, William J. ; Belas, Frank J. ; Sauer, John-Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-b90db9b87e5c35a5ceb1e9ceef6bd94f0cac07d989fa20caf1604f71a6bb61313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>ADHD</topic><topic>Analysis</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Atomoxetine Hydrochloride</topic><topic>Bioanalytical</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Calibration</topic><topic>Chromatography</topic><topic>Chromatography, Liquid</topic><topic>Clinical</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General pharmacology</topic><topic>Glucuronides - blood</topic><topic>Glucuronides - urine</topic><topic>Humans</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Oxidation-Reduction</topic><topic>Pharmacology. Drug treatments</topic><topic>Propylamines - analysis</topic><topic>Propylamines - blood</topic><topic>Propylamines - urine</topic><topic>Quantification</topic><topic>Reference Standards</topic><topic>Reproducibility of Results</topic><topic>Spectrometry, Fluorescence</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>Straterra</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mullen, John H.</creatorcontrib><creatorcontrib>Shugert, Richard L.</creatorcontrib><creatorcontrib>Ponsler, George D.</creatorcontrib><creatorcontrib>Li, Qimin</creatorcontrib><creatorcontrib>Sundaram, Bhaskar</creatorcontrib><creatorcontrib>Coales, Heather L.</creatorcontrib><creatorcontrib>Yakupkovic, Joseph E.</creatorcontrib><creatorcontrib>LeLacheur, Richard M.</creatorcontrib><creatorcontrib>Wheeler, William J.</creatorcontrib><creatorcontrib>Belas, Frank J.</creatorcontrib><creatorcontrib>Sauer, John-Michael</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>Mullen, John H.</au><au>Shugert, Richard L.</au><au>Ponsler, George D.</au><au>Li, Qimin</au><au>Sundaram, Bhaskar</au><au>Coales, Heather L.</au><au>Yakupkovic, Joseph E.</au><au>LeLacheur, Richard M.</au><au>Wheeler, William J.</au><au>Belas, Frank J.</au><au>Sauer, John-Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS)</atitle><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle><addtitle>J Pharm Biomed Anal</addtitle><date>2005-07-15</date><risdate>2005</risdate><volume>38</volume><issue>4</issue><spage>720</spage><epage>733</epage><pages>720-733</pages><issn>0731-7085</issn><eissn>1873-264X</eissn><coden>JPBADA</coden><abstract>A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine,
N-
des-methylatomoxetine, and 4-hydroxyatomoxetine-
O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate and precise for the analytes in all species, resulting in inter-batch accuracy (percent relative error, %RE) within 100
±
13% and inter-batch precision (relative standard deviation, %RSD) within 11%. Stability was demonstrated for the analytes in neat solutions and the reconstitution solvent, as well as plasma and urine (with or without the deconjugation reagent). The method was simple, robust (utilized for the analysis of several hundred clinical study samples), and amenable to high sample throughput.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>15967301</pmid><doi>10.1016/j.jpba.2005.02.007</doi><tpages>14</tpages></addata></record> |
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source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
subjects | ADHD Analysis Analytical, structural and metabolic biochemistry Atomoxetine Hydrochloride Bioanalytical Biological and medical sciences Biotransformation Calibration Chromatography Chromatography, Liquid Clinical Fundamental and applied biological sciences. Psychology General pharmacology Glucuronides - blood Glucuronides - urine Humans Mass Spectrometry Medical sciences Oxidation-Reduction Pharmacology. Drug treatments Propylamines - analysis Propylamines - blood Propylamines - urine Quantification Reference Standards Reproducibility of Results Spectrometry, Fluorescence Spectrophotometry, Ultraviolet Straterra |
title | Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS) |
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