Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging
Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qua...
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| Veröffentlicht in: | Scientific reports 2016-11, Vol.6 (1), p.37648-37648, Article 37648 |
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| creator | Swales, John G. Strittmatter, Nicole Tucker, James W. Clench, Malcolm R. Webborn, Peter J. H. Goodwin, Richard J. A. |
| description | Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported. |
| doi_str_mv | 10.1038/srep37648 |
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H. ; Goodwin, Richard J. A.</creator><creatorcontrib>Swales, John G. ; Strittmatter, Nicole ; Tucker, James W. ; Clench, Malcolm R. ; Webborn, Peter J. H. ; Goodwin, Richard J. A.</creatorcontrib><description>Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep37648</identifier><identifier>PMID: 27883030</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/1438 ; 639/638/11/296 ; Animals ; Calibration ; Chromatography, Liquid - methods ; Humanities and Social Sciences ; Imaging, Three-Dimensional ; Ionization ; Ions ; Limit of Detection ; Liver ; Male ; Mass spectrometry ; Mass spectroscopy ; multidisciplinary ; Organ Specificity ; Pharmaceutical Preparations - analysis ; Qualitative analysis ; Quantitation ; Quantitative research ; Rats, Wistar ; Reference Standards ; Science ; Scientific imaging ; Solvents ; Spatial distribution ; Spectrometry, Mass, Electrospray Ionization ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods ; Tandem Mass Spectrometry ; Tissues</subject><ispartof>Scientific reports, 2016-11, Vol.6 (1), p.37648-37648, Article 37648</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Nov 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-5b4b979b2a5bee6adb23f180ea87d0c1642a42e0ec7baab9caeb12610db664ad3</citedby><cites>FETCH-LOGICAL-c504t-5b4b979b2a5bee6adb23f180ea87d0c1642a42e0ec7baab9caeb12610db664ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121636/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121636/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27883030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Swales, John G.</creatorcontrib><creatorcontrib>Strittmatter, Nicole</creatorcontrib><creatorcontrib>Tucker, James W.</creatorcontrib><creatorcontrib>Clench, Malcolm R.</creatorcontrib><creatorcontrib>Webborn, Peter J. H.</creatorcontrib><creatorcontrib>Goodwin, Richard J. A.</creatorcontrib><title>Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.</description><subject>631/154/1438</subject><subject>639/638/11/296</subject><subject>Animals</subject><subject>Calibration</subject><subject>Chromatography, Liquid - methods</subject><subject>Humanities and Social Sciences</subject><subject>Imaging, Three-Dimensional</subject><subject>Ionization</subject><subject>Ions</subject><subject>Limit of Detection</subject><subject>Liver</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>multidisciplinary</subject><subject>Organ Specificity</subject><subject>Pharmaceutical Preparations - analysis</subject><subject>Qualitative analysis</subject><subject>Quantitation</subject><subject>Quantitative research</subject><subject>Rats, Wistar</subject><subject>Reference Standards</subject><subject>Science</subject><subject>Scientific imaging</subject><subject>Solvents</subject><subject>Spatial distribution</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><subject>Tandem Mass Spectrometry</subject><subject>Tissues</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkUtv1DAUhS0EotW0C_4AssSGIk3xK06yQapKaSsNQmhgHV07TnBJnNQPxPx7PJ12NIA3tnU_n3t8D0KvKDmnhFfvgzczL6WonqFjRkSxZJyx5wfnI3Qawh3Jq2C1oPVLdMTKquKEk2P0cz1DtDDgrwlctDFfJoenDn_0qQ_YOhxtCMkEnIJ1PV7Z-2RbfPU7etAP7Dr5DrTBFw6GTbABf4YQ8Ho2OvppNNFv8O0IfX58gl50MARz-rgv0PdPV98ub5arL9e3lxerpS6IiMtCCVWXtWJQKGMktIrxjlbEQFW2RFMpGAhmiNGlAlC1BqMok5S0SkoBLV-gDzvdOanRtNq4bHZoZm9H8JtmAtv8XXH2R9NPv5qCMiq5zAJvHwX8dJ__HpvRBm2GAZyZUmhoJXgty-0IF-jNP-jdlHwexZaqay6Z4CxTZztK-ynkwLq9GUqabYrNPsXMvj50vyefMsvAux0Qcsn1xh-0_E_tDxC9qVc</recordid><startdate>20161124</startdate><enddate>20161124</enddate><creator>Swales, John G.</creator><creator>Strittmatter, Nicole</creator><creator>Tucker, James W.</creator><creator>Clench, Malcolm R.</creator><creator>Webborn, Peter J. 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A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-5b4b979b2a5bee6adb23f180ea87d0c1642a42e0ec7baab9caeb12610db664ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/154/1438</topic><topic>639/638/11/296</topic><topic>Animals</topic><topic>Calibration</topic><topic>Chromatography, Liquid - methods</topic><topic>Humanities and Social Sciences</topic><topic>Imaging, Three-Dimensional</topic><topic>Ionization</topic><topic>Ions</topic><topic>Limit of Detection</topic><topic>Liver</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>multidisciplinary</topic><topic>Organ Specificity</topic><topic>Pharmaceutical Preparations - analysis</topic><topic>Qualitative analysis</topic><topic>Quantitation</topic><topic>Quantitative research</topic><topic>Rats, Wistar</topic><topic>Reference Standards</topic><topic>Science</topic><topic>Scientific imaging</topic><topic>Solvents</topic><topic>Spatial distribution</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</topic><topic>Tandem Mass Spectrometry</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Swales, John G.</creatorcontrib><creatorcontrib>Strittmatter, Nicole</creatorcontrib><creatorcontrib>Tucker, James W.</creatorcontrib><creatorcontrib>Clench, Malcolm R.</creatorcontrib><creatorcontrib>Webborn, Peter J. 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H.</au><au>Goodwin, Richard J. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-11-24</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>37648</spage><epage>37648</epage><pages>37648-37648</pages><artnum>37648</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27883030</pmid><doi>10.1038/srep37648</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/154/1438 639/638/11/296 Animals Calibration Chromatography, Liquid - methods Humanities and Social Sciences Imaging, Three-Dimensional Ionization Ions Limit of Detection Liver Male Mass spectrometry Mass spectroscopy multidisciplinary Organ Specificity Pharmaceutical Preparations - analysis Qualitative analysis Quantitation Quantitative research Rats, Wistar Reference Standards Science Scientific imaging Solvents Spatial distribution Spectrometry, Mass, Electrospray Ionization Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods Tandem Mass Spectrometry Tissues |
| title | Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging |
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