Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS
•A LC–MS determination method of cabozantinib in plasma and tissues was developed.•The pharmacokinetic study of cabozantinib in rats was investigated.•The distribution of cabozantinib in tissues was studied.•A BP-ANN tissue distribution model of cabozantinib in rat was developed. Cabozantinib (XL184...
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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, 2015-03, Vol.983-984, p.125-131 |
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| container_title | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences |
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| creator | Wang, Xianqin Wang, Shuanghu Lin, Feiyan Zhang, Qingwei Chen, HuiLing Wang, Xianchuan Wen, Congcong Ma, Jianshe Hu, Lufeng |
| description | •A LC–MS determination method of cabozantinib in plasma and tissues was developed.•The pharmacokinetic study of cabozantinib in rats was investigated.•The distribution of cabozantinib in tissues was studied.•A BP-ANN tissue distribution model of cabozantinib in rat was developed.
Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal–epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5–5000ng/mL (r2>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC–MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration–time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues. |
| doi_str_mv | 10.1016/j.jchromb.2015.01.020 |
| format | Article |
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Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal–epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5–5000ng/mL (r2>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC–MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration–time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues.</description><identifier>ISSN: 1570-0232</identifier><identifier>EISSN: 1873-376X</identifier><identifier>DOI: 10.1016/j.jchromb.2015.01.020</identifier><identifier>PMID: 25638029</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anilides - administration & dosage ; Anilides - blood ; Anilides - chemistry ; Anilides - pharmacokinetics ; Animals ; Blood ; BP-ANN ; Cabozantinib ; Calibration ; Chromatography ; Chromatography, High Pressure Liquid - methods ; Drug Stability ; Inhibitors ; Kidneys ; Kinases ; Liquids ; Liver - metabolism ; Mathematical models ; Midazolam - chemistry ; Neural Networks (Computer) ; Pharmacokinetics ; Pyridines - administration & dosage ; Pyridines - blood ; Pyridines - chemistry ; Pyridines - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry - methods ; Tissue Distribution ; UPLC–MS/MS</subject><ispartof>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2015-03, Vol.983-984, p.125-131</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-73285e2119bfc3666228077fa8680e174878d99c1660ad0caf1f168e9b3b15ad3</citedby><cites>FETCH-LOGICAL-c464t-73285e2119bfc3666228077fa8680e174878d99c1660ad0caf1f168e9b3b15ad3</cites><orcidid>0000-0002-3494-2405</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jchromb.2015.01.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25638029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xianqin</creatorcontrib><creatorcontrib>Wang, Shuanghu</creatorcontrib><creatorcontrib>Lin, Feiyan</creatorcontrib><creatorcontrib>Zhang, Qingwei</creatorcontrib><creatorcontrib>Chen, HuiLing</creatorcontrib><creatorcontrib>Wang, Xianchuan</creatorcontrib><creatorcontrib>Wen, Congcong</creatorcontrib><creatorcontrib>Ma, Jianshe</creatorcontrib><creatorcontrib>Hu, Lufeng</creatorcontrib><title>Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS</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>•A LC–MS determination method of cabozantinib in plasma and tissues was developed.•The pharmacokinetic study of cabozantinib in rats was investigated.•The distribution of cabozantinib in tissues was studied.•A BP-ANN tissue distribution model of cabozantinib in rat was developed.
Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal–epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5–5000ng/mL (r2>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC–MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration–time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues.</description><subject>Anilides - administration & dosage</subject><subject>Anilides - blood</subject><subject>Anilides - chemistry</subject><subject>Anilides - pharmacokinetics</subject><subject>Animals</subject><subject>Blood</subject><subject>BP-ANN</subject><subject>Cabozantinib</subject><subject>Calibration</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Drug Stability</subject><subject>Inhibitors</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Liquids</subject><subject>Liver - metabolism</subject><subject>Mathematical models</subject><subject>Midazolam - chemistry</subject><subject>Neural Networks (Computer)</subject><subject>Pharmacokinetics</subject><subject>Pyridines - administration & dosage</subject><subject>Pyridines - blood</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reproducibility of Results</subject><subject>Tandem Mass Spectrometry - methods</subject><subject>Tissue Distribution</subject><subject>UPLC–MS/MS</subject><issn>1570-0232</issn><issn>1873-376X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuFDEQRS0EIiHwCSAv2XTHj_GjVwiNwkOaiEghEjvjR7XiYbodbDdSWOUf8od8CY5mYAurqsW5t1T3IvSSkp4SKk-3_dZf5zS5nhEqekJ7wsgjdEy14h1X8svjtgtFOsI4O0LPStkSQhVR_Ck6YkJyTdhwjL5eXNs8WZ--xRlq9AXbOeAaS1kAh1hqjm6pMc14SgF2OI3YW5d-2rnGOTocZ5xtxQEq5KlZBOxu8dXFZv3r7v788vT88jl6MtpdgReHeYKu3p19Xn_oNp_ef1y_3XR-JVe1U5xpAYzSwY2eSykZ00Sp0WqpCVC10kqHYfBUSmID8XakI5UaBscdFTbwE_R673uT0_cFSjVTLB52OztDWoppwkGL9jP7D1RwysRK0YaKPepzKiXDaG5ynGy-NZSYhx7M1hx6MA89GEJN66HpXh1OLG6C8Ff1J_gGvNkD0DL5ESGb4iPMHkLM4KsJKf7jxG-QA5vz</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Wang, Xianqin</creator><creator>Wang, Shuanghu</creator><creator>Lin, Feiyan</creator><creator>Zhang, Qingwei</creator><creator>Chen, HuiLing</creator><creator>Wang, Xianchuan</creator><creator>Wen, Congcong</creator><creator>Ma, Jianshe</creator><creator>Hu, Lufeng</creator><general>Elsevier B.V</general><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><scope>7TB</scope><scope>8FD</scope><scope>FR3</scope><orcidid>https://orcid.org/0000-0002-3494-2405</orcidid></search><sort><creationdate>20150301</creationdate><title>Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS</title><author>Wang, Xianqin ; Wang, Shuanghu ; Lin, Feiyan ; Zhang, Qingwei ; Chen, HuiLing ; Wang, Xianchuan ; Wen, Congcong ; Ma, Jianshe ; Hu, Lufeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-73285e2119bfc3666228077fa8680e174878d99c1660ad0caf1f168e9b3b15ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anilides - administration & dosage</topic><topic>Anilides - blood</topic><topic>Anilides - chemistry</topic><topic>Anilides - pharmacokinetics</topic><topic>Animals</topic><topic>Blood</topic><topic>BP-ANN</topic><topic>Cabozantinib</topic><topic>Calibration</topic><topic>Chromatography</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Drug Stability</topic><topic>Inhibitors</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>Liquids</topic><topic>Liver - metabolism</topic><topic>Mathematical models</topic><topic>Midazolam - chemistry</topic><topic>Neural Networks (Computer)</topic><topic>Pharmacokinetics</topic><topic>Pyridines - administration & dosage</topic><topic>Pyridines - blood</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reproducibility of Results</topic><topic>Tandem Mass Spectrometry - methods</topic><topic>Tissue Distribution</topic><topic>UPLC–MS/MS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xianqin</creatorcontrib><creatorcontrib>Wang, Shuanghu</creatorcontrib><creatorcontrib>Lin, Feiyan</creatorcontrib><creatorcontrib>Zhang, Qingwei</creatorcontrib><creatorcontrib>Chen, HuiLing</creatorcontrib><creatorcontrib>Wang, Xianchuan</creatorcontrib><creatorcontrib>Wen, Congcong</creatorcontrib><creatorcontrib>Ma, Jianshe</creatorcontrib><creatorcontrib>Hu, Lufeng</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><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><jtitle>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xianqin</au><au>Wang, Shuanghu</au><au>Lin, Feiyan</au><au>Zhang, Qingwei</au><au>Chen, HuiLing</au><au>Wang, Xianchuan</au><au>Wen, Congcong</au><au>Ma, Jianshe</au><au>Hu, Lufeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS</atitle><jtitle>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</jtitle><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>983-984</volume><spage>125</spage><epage>131</epage><pages>125-131</pages><issn>1570-0232</issn><eissn>1873-376X</eissn><abstract>•A LC–MS determination method of cabozantinib in plasma and tissues was developed.•The pharmacokinetic study of cabozantinib in rats was investigated.•The distribution of cabozantinib in tissues was studied.•A BP-ANN tissue distribution model of cabozantinib in rat was developed.
Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal–epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5–5000ng/mL (r2>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC–MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration–time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25638029</pmid><doi>10.1016/j.jchromb.2015.01.020</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3494-2405</orcidid></addata></record> |
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| subjects | Anilides - administration & dosage Anilides - blood Anilides - chemistry Anilides - pharmacokinetics Animals Blood BP-ANN Cabozantinib Calibration Chromatography Chromatography, High Pressure Liquid - methods Drug Stability Inhibitors Kidneys Kinases Liquids Liver - metabolism Mathematical models Midazolam - chemistry Neural Networks (Computer) Pharmacokinetics Pyridines - administration & dosage Pyridines - blood Pyridines - chemistry Pyridines - pharmacokinetics Rats Rats, Sprague-Dawley Reproducibility of Results Tandem Mass Spectrometry - methods Tissue Distribution UPLC–MS/MS |
| title | Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS |
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