Determination of atomoxetine metabolites in human plasma by liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study
DC Field | Value | Language |
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dc.contributor.author | Choi, Chang-Ik | - |
dc.contributor.author | Bae, Jung-Woo | - |
dc.contributor.author | Lee, Hye-In | - |
dc.contributor.author | Jang, Choon-Gon | - |
dc.contributor.author | Sohn, Uy Dong | - |
dc.contributor.author | Lee, Seok-Yong | - |
dc.date.available | 2019-05-29T07:41:31Z | - |
dc.date.issued | 2012-02 | - |
dc.identifier.issn | 1570-0232 | - |
dc.identifier.issn | 1873-376X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20511 | - |
dc.description.abstract | 4-Hydroxyatomoxetine (4-HAT) and N-desmethylatomoxetine (N-DAT) are major metabolites of atomoxetine, a potent and selective inhibitor of the presynaptic norepinephrine transporter that is used for the treatment of attention deficit/hyperactivity disorder. The pharmacological activity of 4-HAT is similar to that of atomoxetine. We have developed and validated a simple, rapid and sensitive liquid chromatography analytical method with tandem mass spectrometry (LC-MS/MS) for the determination of 4-HAT and N-DAT in human plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of analytes was performed using a reversed-phase Luna C-18 column (2.0 mm x 100 mm, 3 vim particles) with a mobile phase of 10 mM ammonium formate buffer (pH 3.5)-methanol (10:90, v/v) and quantified by MS/MS detection in ESI positive ion mode. The flow rate of the mobile phase was 250 mu L/min and the retention times of 4-HAT, N-DAT and internal standard (IS, metoprolol) were 0.9, 1.0 and 1.0 min, respectively. The calibration curves were linear over the range of 0.05-20 ng/mL for 4-HAT and 0.1-20 ng/mL for N-DAT. The lower limits of quantification, using 200 mu L human plasma, were 0.05 and 0.1 ng/mL for 4-HAT and N-DAT, respectively. The mean accuracy and precision for intra- and inter-day validation of 4-HAT and N-DAT were both within the acceptable limits. This LC-MS/MS method showed improved sensitivity for quantification of the two main metabolites of atomoxetine in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans. (C) 2011 Elsevier B.V. All rights reserved. | - |
dc.format.extent | 6 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | Determination of atomoxetine metabolites in human plasma by liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.jchromb.2011.12.023 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v.885, pp 103 - 108 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000301563400015 | - |
dc.identifier.scopusid | 2-s2.0-84856649492 | - |
dc.citation.endPage | 108 | - |
dc.citation.startPage | 103 | - |
dc.citation.title | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | - |
dc.citation.volume | 885 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | 4-Hydroxyatomoxetine | - |
dc.subject.keywordAuthor | N-Desmethylatomoxetine | - |
dc.subject.keywordAuthor | LC-MS/MS | - |
dc.subject.keywordAuthor | Human plasma | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordPlus | RAT-BRAIN | - |
dc.subject.keywordPlus | NOREPINEPHRINE | - |
dc.subject.keywordPlus | QUANTIFICATION | - |
dc.subject.keywordPlus | HYDROCHLORIDE | - |
dc.subject.keywordPlus | DISPOSITION | - |
dc.subject.keywordPlus | LIGAND | - |
dc.subject.keywordPlus | HPLC | - |
dc.subject.keywordPlus | FATE | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemical Research Methods | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Analytical | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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