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
Hauptverfasser: 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
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container_end_page 733
container_issue 4
container_start_page 720
container_title Journal of pharmaceutical and biomedical analysis
container_volume 38
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
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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). 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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. 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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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