Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma
The development of metal‐based chemotherapeutics lacks methods which are capable of providing early indication on the potential of new metal complexes as future anticancer drugs. Since most of these compounds are administered intravenously, serum proteins are the first available biological binding p...
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Veröffentlicht in: | Electrophoresis 2008-05, Vol.29 (10), p.2224-2232 |
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description | The development of metal‐based chemotherapeutics lacks methods which are capable of providing early indication on the potential of new metal complexes as future anticancer drugs. Since most of these compounds are administered intravenously, serum proteins are the first available biological binding partners in the bloodstream. For platinum‐based anticancer drugs the interaction with serum proteins is regarded as an important contribution to the side effects accompanying chemotherapy. In contrast, newly developed ruthenium compounds are thought to be transported into the tumor in a protein‐bound form. In here, the application of CE hyphenated to inductively coupled plasma (ICP)‐MS, applying Polybrene‐coated capillaries, is demonstrated for studying the interaction of indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)] (KP1019) with HSA and transferrin, which are important transport proteins. Furthermore, the applicability of the method to human serum and plasma and, more importantly, to real‐world patient samples was proven. KP1019 was found to bind to a high degree to HSA both in serum, plasma and the patient samples. Only minor fractions of ruthenium were found attached to other proteins. |
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Since most of these compounds are administered intravenously, serum proteins are the first available biological binding partners in the bloodstream. For platinum‐based anticancer drugs the interaction with serum proteins is regarded as an important contribution to the side effects accompanying chemotherapy. In contrast, newly developed ruthenium compounds are thought to be transported into the tumor in a protein‐bound form. In here, the application of CE hyphenated to inductively coupled plasma (ICP)‐MS, applying Polybrene‐coated capillaries, is demonstrated for studying the interaction of indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)] (KP1019) with HSA and transferrin, which are important transport proteins. Furthermore, the applicability of the method to human serum and plasma and, more importantly, to real‐world patient samples was proven. KP1019 was found to bind to a high degree to HSA both in serum, plasma and the patient samples. Only minor fractions of ruthenium were found attached to other proteins.</description><identifier>ISSN: 0173-0835</identifier><identifier>EISSN: 1522-2683</identifier><identifier>DOI: 10.1002/elps.200780790</identifier><identifier>PMID: 18512673</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Anticancer chemotherapeutics ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - blood ; Blood Chemical Analysis - methods ; Blood Proteins - metabolism ; Capillary electrophoresis ; Electrophoresis, Capillary - methods ; Humans ; In Vitro Techniques ; Indazoles - administration & dosage ; Indazoles - blood ; Inductively coupled plasma-mass spectrometry ; Mass Spectrometry - methods ; Neoplasms - blood ; Neoplasms - drug therapy ; Organometallic Compounds - administration & dosage ; Organometallic Compounds - blood ; Protein Binding ; Protein interaction ; Ruthenium complex ; Ruthenium Compounds - administration & dosage ; Ruthenium Compounds - blood ; Serum Albumin - metabolism ; Transferrin - metabolism</subject><ispartof>Electrophoresis, 2008-05, Vol.29 (10), p.2224-2232</ispartof><rights>Copyright © 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4830-fc84efb788fc9ea4dab55fa25b78c2f9ee7fe442ad765996528ff7800a94934b3</citedby><cites>FETCH-LOGICAL-c4830-fc84efb788fc9ea4dab55fa25b78c2f9ee7fe442ad765996528ff7800a94934b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Felps.200780790$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Felps.200780790$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18512673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Groessl, Michael</creatorcontrib><creatorcontrib>Hartinger, Christian G.</creatorcontrib><creatorcontrib>Polec-Pawlak, Kasia</creatorcontrib><creatorcontrib>Jarosz, Maciej</creatorcontrib><creatorcontrib>Keppler, Bernhard K.</creatorcontrib><title>Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma</title><title>Electrophoresis</title><addtitle>ELECTROPHORESIS</addtitle><description>The development of metal‐based chemotherapeutics lacks methods which are capable of providing early indication on the potential of new metal complexes as future anticancer drugs. Since most of these compounds are administered intravenously, serum proteins are the first available biological binding partners in the bloodstream. For platinum‐based anticancer drugs the interaction with serum proteins is regarded as an important contribution to the side effects accompanying chemotherapy. In contrast, newly developed ruthenium compounds are thought to be transported into the tumor in a protein‐bound form. In here, the application of CE hyphenated to inductively coupled plasma (ICP)‐MS, applying Polybrene‐coated capillaries, is demonstrated for studying the interaction of indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)] (KP1019) with HSA and transferrin, which are important transport proteins. Furthermore, the applicability of the method to human serum and plasma and, more importantly, to real‐world patient samples was proven. KP1019 was found to bind to a high degree to HSA both in serum, plasma and the patient samples. Only minor fractions of ruthenium were found attached to other proteins.</description><subject>Anticancer chemotherapeutics</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - blood</subject><subject>Blood Chemical Analysis - methods</subject><subject>Blood Proteins - metabolism</subject><subject>Capillary electrophoresis</subject><subject>Electrophoresis, Capillary - methods</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Indazoles - administration & dosage</subject><subject>Indazoles - blood</subject><subject>Inductively coupled plasma-mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - drug therapy</subject><subject>Organometallic Compounds - administration & dosage</subject><subject>Organometallic Compounds - blood</subject><subject>Protein Binding</subject><subject>Protein interaction</subject><subject>Ruthenium complex</subject><subject>Ruthenium Compounds - administration & dosage</subject><subject>Ruthenium Compounds - blood</subject><subject>Serum Albumin - metabolism</subject><subject>Transferrin - metabolism</subject><issn>0173-0835</issn><issn>1522-2683</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxSMEokvhyhH5xC1b_01ibtWqXVBXLYKiHi2vMyYBJ07tBMh34kPiZZfS21481uj33ozmZdlrgpcEY3oGbohLinFZ4VLiJ9mCCEpzWlTsabbApGQ5rpg4yV7E-A1jzCXnz7MTUglCi5Itst8rPbTO6TAjcGDG4IfGB4htRM08NNDrEWo0etT29WTG9ge4GRk_DS61B6djp_NOx4ji8FfdwRjmd-gc9T6hSA9D8No0yPqAxgaQ7rWbd-7epv_YGt0bCCjJtHO-DtPXmEahZup0jyKEqUvYv0kvs2dWuwivDvU0-3J5cbt6n29u1h9W55vc8Irh3JqKg92WVWWNBM1rvRXCaipSy1ArAUoLnFNdl4WQshC0sjYdEGvJJeNbdpq93fum5e8niKPq2mggnakHP0VVSEYoTe8xkDEhWMnZUZASgmnBcAKXe9AEH2MAq4bQdikeRbDaJa52iauHxJPgzcF52nZQ_8cPESdA7oGfrYP5iJ262Hz8_Ng832vbOMKvB60O31WyLoW6u16r209Xl3dkda3W7A-H88zX</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Groessl, Michael</creator><creator>Hartinger, Christian G.</creator><creator>Polec-Pawlak, Kasia</creator><creator>Jarosz, Maciej</creator><creator>Keppler, Bernhard K.</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>BSCLL</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>7QO</scope><scope>7T2</scope><scope>7U2</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7U5</scope><scope>L7M</scope><scope>7X8</scope></search><sort><creationdate>20080501</creationdate><title>Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma</title><author>Groessl, Michael ; Hartinger, Christian G. ; Polec-Pawlak, Kasia ; Jarosz, Maciej ; Keppler, Bernhard K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4830-fc84efb788fc9ea4dab55fa25b78c2f9ee7fe442ad765996528ff7800a94934b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Anticancer chemotherapeutics</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - blood</topic><topic>Blood Chemical Analysis - methods</topic><topic>Blood Proteins - metabolism</topic><topic>Capillary electrophoresis</topic><topic>Electrophoresis, Capillary - methods</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Indazoles - administration & dosage</topic><topic>Indazoles - blood</topic><topic>Inductively coupled plasma-mass spectrometry</topic><topic>Mass Spectrometry - methods</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - drug therapy</topic><topic>Organometallic Compounds - administration & dosage</topic><topic>Organometallic Compounds - blood</topic><topic>Protein Binding</topic><topic>Protein interaction</topic><topic>Ruthenium complex</topic><topic>Ruthenium Compounds - administration & dosage</topic><topic>Ruthenium Compounds - blood</topic><topic>Serum Albumin - metabolism</topic><topic>Transferrin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Groessl, Michael</creatorcontrib><creatorcontrib>Hartinger, Christian G.</creatorcontrib><creatorcontrib>Polec-Pawlak, Kasia</creatorcontrib><creatorcontrib>Jarosz, Maciej</creatorcontrib><creatorcontrib>Keppler, Bernhard K.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Electrophoresis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Groessl, Michael</au><au>Hartinger, Christian G.</au><au>Polec-Pawlak, Kasia</au><au>Jarosz, Maciej</au><au>Keppler, Bernhard K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma</atitle><jtitle>Electrophoresis</jtitle><addtitle>ELECTROPHORESIS</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>29</volume><issue>10</issue><spage>2224</spage><epage>2232</epage><pages>2224-2232</pages><issn>0173-0835</issn><eissn>1522-2683</eissn><abstract>The development of metal‐based chemotherapeutics lacks methods which are capable of providing early indication on the potential of new metal complexes as future anticancer drugs. Since most of these compounds are administered intravenously, serum proteins are the first available biological binding partners in the bloodstream. For platinum‐based anticancer drugs the interaction with serum proteins is regarded as an important contribution to the side effects accompanying chemotherapy. In contrast, newly developed ruthenium compounds are thought to be transported into the tumor in a protein‐bound form. In here, the application of CE hyphenated to inductively coupled plasma (ICP)‐MS, applying Polybrene‐coated capillaries, is demonstrated for studying the interaction of indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)] (KP1019) with HSA and transferrin, which are important transport proteins. Furthermore, the applicability of the method to human serum and plasma and, more importantly, to real‐world patient samples was proven. KP1019 was found to bind to a high degree to HSA both in serum, plasma and the patient samples. Only minor fractions of ruthenium were found attached to other proteins.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>18512673</pmid><doi>10.1002/elps.200780790</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anticancer chemotherapeutics Antineoplastic Agents - administration & dosage Antineoplastic Agents - blood Blood Chemical Analysis - methods Blood Proteins - metabolism Capillary electrophoresis Electrophoresis, Capillary - methods Humans In Vitro Techniques Indazoles - administration & dosage Indazoles - blood Inductively coupled plasma-mass spectrometry Mass Spectrometry - methods Neoplasms - blood Neoplasms - drug therapy Organometallic Compounds - administration & dosage Organometallic Compounds - blood Protein Binding Protein interaction Ruthenium complex Ruthenium Compounds - administration & dosage Ruthenium Compounds - blood Serum Albumin - metabolism Transferrin - metabolism |
title | Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma |
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