Analysis of intracellular doxorubicin and its metabolites by ultra-high-performance liquid chromatography
Doxorubicin, a highly effective anticancer drug, produces severe side effect such as cardiotoxicity, which is mainly caused by its metabolite, doxorubicinol. While in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular...
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| Veröffentlicht in: | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2010-06, Vol.878 (19), p.1466-1470 |
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| container_title | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences |
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| creator | Sakai-Kato, Kumiko Saito, Eiko Ishikura, Keiko Kawanishi, Toru |
| description | Doxorubicin, a highly effective anticancer drug, produces severe side effect such as cardiotoxicity, which is mainly caused by its metabolite, doxorubicinol. While
in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular concentration of the metabolites. In this report, we developed a sensitive and high-throughput method for measuring cellular concentrations of doxorubicin and its metabolites by ultra-high-performance liquid chromatography. The method achieved more than 96% recovery of doxorubicin and its metabolites from cell homogenates. Using simple separation conditions, doxorubicin and its three main metabolites, and the internal standard, were separated within 3
min. The method has a limit of quantification of 17.4
pg (32.0
fmol) injected doxorubicin. This high sensitivity enables the detection and intracellular quantification of doxorubicin and its metabolite, doxorubicinol, in cell homogenates, and its use will facilitate studies of the relationship between doxorubicin pharmacokinetics and therapeutic outcome. |
| doi_str_mv | 10.1016/j.jchromb.2010.03.040 |
| format | Article |
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in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular concentration of the metabolites. In this report, we developed a sensitive and high-throughput method for measuring cellular concentrations of doxorubicin and its metabolites by ultra-high-performance liquid chromatography. The method achieved more than 96% recovery of doxorubicin and its metabolites from cell homogenates. Using simple separation conditions, doxorubicin and its three main metabolites, and the internal standard, were separated within 3
min. The method has a limit of quantification of 17.4
pg (32.0
fmol) injected doxorubicin. This high sensitivity enables the detection and intracellular quantification of doxorubicin and its metabolite, doxorubicinol, in cell homogenates, and its use will facilitate studies of the relationship between doxorubicin pharmacokinetics and therapeutic outcome.</description><identifier>ISSN: 1570-0232</identifier><identifier>EISSN: 1873-376X</identifier><identifier>DOI: 10.1016/j.jchromb.2010.03.040</identifier><identifier>PMID: 20392674</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Analysis ; Analytical, structural and metabolic biochemistry ; Biological and medical sciences ; Chromatography, High Pressure Liquid - methods ; Doxorubicin ; Doxorubicin - analogs & derivatives ; Doxorubicin - analysis ; Doxorubicin - chemistry ; Doxorubicinol ; Fundamental and applied biological sciences. Psychology ; General pharmacology ; HeLa Cells ; HT29 Cells ; Humans ; Intracellular Space ; Linear Models ; Medical sciences ; Pharmacology. Drug treatments ; Sensitivity and Specificity ; Ultra-high-performance liquid chromatography</subject><ispartof>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2010-06, Vol.878 (19), p.1466-1470</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-655576ef3f139dbcf85920322abf16b6a4667c530e7e318869d51ba633fb37eb3</citedby><cites>FETCH-LOGICAL-c521t-655576ef3f139dbcf85920322abf16b6a4667c530e7e318869d51ba633fb37eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jchromb.2010.03.040$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22912668$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20392674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakai-Kato, Kumiko</creatorcontrib><creatorcontrib>Saito, Eiko</creatorcontrib><creatorcontrib>Ishikura, Keiko</creatorcontrib><creatorcontrib>Kawanishi, Toru</creatorcontrib><title>Analysis of intracellular doxorubicin and its metabolites by ultra-high-performance liquid chromatography</title><title>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</title><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><description>Doxorubicin, a highly effective anticancer drug, produces severe side effect such as cardiotoxicity, which is mainly caused by its metabolite, doxorubicinol. While
in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular concentration of the metabolites. In this report, we developed a sensitive and high-throughput method for measuring cellular concentrations of doxorubicin and its metabolites by ultra-high-performance liquid chromatography. The method achieved more than 96% recovery of doxorubicin and its metabolites from cell homogenates. Using simple separation conditions, doxorubicin and its three main metabolites, and the internal standard, were separated within 3
min. The method has a limit of quantification of 17.4
pg (32.0
fmol) injected doxorubicin. This high sensitivity enables the detection and intracellular quantification of doxorubicin and its metabolite, doxorubicinol, in cell homogenates, and its use will facilitate studies of the relationship between doxorubicin pharmacokinetics and therapeutic outcome.</description><subject>Analysis</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Doxorubicin</subject><subject>Doxorubicin - analogs & derivatives</subject><subject>Doxorubicin - analysis</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicinol</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General pharmacology</subject><subject>HeLa Cells</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Intracellular Space</subject><subject>Linear Models</subject><subject>Medical sciences</subject><subject>Pharmacology. 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Psychology</topic><topic>General pharmacology</topic><topic>HeLa Cells</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Intracellular Space</topic><topic>Linear Models</topic><topic>Medical sciences</topic><topic>Pharmacology. 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in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular concentration of the metabolites. In this report, we developed a sensitive and high-throughput method for measuring cellular concentrations of doxorubicin and its metabolites by ultra-high-performance liquid chromatography. The method achieved more than 96% recovery of doxorubicin and its metabolites from cell homogenates. Using simple separation conditions, doxorubicin and its three main metabolites, and the internal standard, were separated within 3
min. The method has a limit of quantification of 17.4
pg (32.0
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| subjects | Analysis Analytical, structural and metabolic biochemistry Biological and medical sciences Chromatography, High Pressure Liquid - methods Doxorubicin Doxorubicin - analogs & derivatives Doxorubicin - analysis Doxorubicin - chemistry Doxorubicinol Fundamental and applied biological sciences. Psychology General pharmacology HeLa Cells HT29 Cells Humans Intracellular Space Linear Models Medical sciences Pharmacology. Drug treatments Sensitivity and Specificity Ultra-high-performance liquid chromatography |
| title | Analysis of intracellular doxorubicin and its metabolites by ultra-high-performance liquid chromatography |
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