Quantification of Nerve Agent VX-Butyrylcholinesterase Adduct Biomarker from an Accidental Exposure
The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-le...
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Veröffentlicht in: | Journal of analytical toxicology 2008-01, Vol.32 (1), p.68-72 |
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creator | Solano, Maria I. Thomas, Jerry D. Taylor, James T. McGuire, Jeffrey M. Jakubowski, Edward M. Thomson, Sandra A. Maggio, Vincent L. Holland, Kerry E. Smith, J. Richard Capacio, Benedict Woolfitt, Adrian R. Ashley, David L. Barr, John R. |
description | The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80nM, it can be calculated that inhibition levels of ≥ 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX. |
doi_str_mv | 10.1093/jat/32.1.68 |
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Richard ; Capacio, Benedict ; Woolfitt, Adrian R. ; Ashley, David L. ; Barr, John R.</creator><creatorcontrib>Solano, Maria I. ; Thomas, Jerry D. ; Taylor, James T. ; McGuire, Jeffrey M. ; Jakubowski, Edward M. ; Thomson, Sandra A. ; Maggio, Vincent L. ; Holland, Kerry E. ; Smith, J. Richard ; Capacio, Benedict ; Woolfitt, Adrian R. ; Ashley, David L. ; Barr, John R.</creatorcontrib><description>The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80nM, it can be calculated that inhibition levels of ≥ 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.</description><identifier>ISSN: 0146-4760</identifier><identifier>EISSN: 1945-2403</identifier><identifier>DOI: 10.1093/jat/32.1.68</identifier><identifier>PMID: 18269796</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Biomarkers - analysis ; Biomarkers - blood ; Butyrylcholinesterase - chemistry ; Butyrylcholinesterase - metabolism ; Calibration ; Chemical Warfare Agents - analysis ; Chemical Warfare Agents - metabolism ; Cholinesterase Inhibitors - blood ; Cholinesterase Inhibitors - metabolism ; Environmental Exposure - analysis ; Environmental Monitoring - methods ; Fluorides - chemistry ; Gas Chromatography-Mass Spectrometry - methods ; Humans ; Organothiophosphorus Compounds - blood ; Organothiophosphorus Compounds - chemistry ; Organothiophosphorus Compounds - metabolism ; Potassium Compounds - chemistry</subject><ispartof>Journal of analytical toxicology, 2008-01, Vol.32 (1), p.68-72</ispartof><rights>2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-dc4e96fadbaa812c4a95319d32015de88095dbecbe689062fc9dddd3c562a3df3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18269796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Solano, Maria I.</creatorcontrib><creatorcontrib>Thomas, Jerry D.</creatorcontrib><creatorcontrib>Taylor, James T.</creatorcontrib><creatorcontrib>McGuire, Jeffrey M.</creatorcontrib><creatorcontrib>Jakubowski, Edward M.</creatorcontrib><creatorcontrib>Thomson, Sandra A.</creatorcontrib><creatorcontrib>Maggio, Vincent L.</creatorcontrib><creatorcontrib>Holland, Kerry E.</creatorcontrib><creatorcontrib>Smith, J. Richard</creatorcontrib><creatorcontrib>Capacio, Benedict</creatorcontrib><creatorcontrib>Woolfitt, Adrian R.</creatorcontrib><creatorcontrib>Ashley, David L.</creatorcontrib><creatorcontrib>Barr, John R.</creatorcontrib><title>Quantification of Nerve Agent VX-Butyrylcholinesterase Adduct Biomarker from an Accidental Exposure</title><title>Journal of analytical toxicology</title><addtitle>Journal of Analytical Toxicology</addtitle><addtitle>Journal of Analytical Toxicology</addtitle><description>The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80nM, it can be calculated that inhibition levels of ≥ 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.</description><subject>Biomarkers - analysis</subject><subject>Biomarkers - blood</subject><subject>Butyrylcholinesterase - chemistry</subject><subject>Butyrylcholinesterase - metabolism</subject><subject>Calibration</subject><subject>Chemical Warfare Agents - analysis</subject><subject>Chemical Warfare Agents - metabolism</subject><subject>Cholinesterase Inhibitors - blood</subject><subject>Cholinesterase Inhibitors - metabolism</subject><subject>Environmental Exposure - analysis</subject><subject>Environmental Monitoring - methods</subject><subject>Fluorides - chemistry</subject><subject>Gas Chromatography-Mass Spectrometry - methods</subject><subject>Humans</subject><subject>Organothiophosphorus Compounds - blood</subject><subject>Organothiophosphorus Compounds - chemistry</subject><subject>Organothiophosphorus Compounds - metabolism</subject><subject>Potassium Compounds - chemistry</subject><issn>0146-4760</issn><issn>1945-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDlPAzEQRi0EgnBU9MgVDdrga712GW4Qh5C4RGM5thcMm3WwdxH59xglghI3U_jNNzMPgG2MhhhJuv-mu31KhnjIxRIYYMnKgjBEl8EAYcYLVnG0BtZTekMIc8HpKljDgnBZST4A5rbXbedrb3TnQwtDDa9d_HRw9OLaDj48FQd9N4uzxryGxrcudS7qlL-t7U0HD3yY6PjuIqxjmEDdwpEx3uZW3cDjr2lIfXSbYKXWTXJbi7oB7k-O7w7Pisub0_PD0WVhmGBdYQ1zktfajrUWmBimZUmxtJQgXFonBJKlHTszdlxIxEltpM2PmpITTW1NN8DuPHcaw0efV1UTn4xrGt260CdFMCoxJvxfEMtSUEJpBvfmoIkhpehqNY0-HzxTGKkf-SrLV5QorLjI9M4ith9PnP1jF7b_5oZ--k9SMQd99v31i2bTile0KtXZ07O6qB7l6ckVU0f0G1VQnWk</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>Solano, Maria I.</creator><creator>Thomas, Jerry D.</creator><creator>Taylor, James T.</creator><creator>McGuire, Jeffrey M.</creator><creator>Jakubowski, Edward M.</creator><creator>Thomson, Sandra A.</creator><creator>Maggio, Vincent L.</creator><creator>Holland, Kerry E.</creator><creator>Smith, J. Richard</creator><creator>Capacio, Benedict</creator><creator>Woolfitt, Adrian R.</creator><creator>Ashley, David L.</creator><creator>Barr, John R.</creator><general>Oxford University Press</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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20080101</creationdate><title>Quantification of Nerve Agent VX-Butyrylcholinesterase Adduct Biomarker from an Accidental Exposure</title><author>Solano, Maria I. ; Thomas, Jerry D. ; Taylor, James T. ; McGuire, Jeffrey M. ; Jakubowski, Edward M. ; Thomson, Sandra A. ; Maggio, Vincent L. ; Holland, Kerry E. ; Smith, J. Richard ; Capacio, Benedict ; Woolfitt, Adrian R. ; Ashley, David L. ; Barr, John R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-dc4e96fadbaa812c4a95319d32015de88095dbecbe689062fc9dddd3c562a3df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biomarkers - analysis</topic><topic>Biomarkers - blood</topic><topic>Butyrylcholinesterase - chemistry</topic><topic>Butyrylcholinesterase - metabolism</topic><topic>Calibration</topic><topic>Chemical Warfare Agents - analysis</topic><topic>Chemical Warfare Agents - metabolism</topic><topic>Cholinesterase Inhibitors - blood</topic><topic>Cholinesterase Inhibitors - metabolism</topic><topic>Environmental Exposure - analysis</topic><topic>Environmental Monitoring - methods</topic><topic>Fluorides - chemistry</topic><topic>Gas Chromatography-Mass Spectrometry - methods</topic><topic>Humans</topic><topic>Organothiophosphorus Compounds - blood</topic><topic>Organothiophosphorus Compounds - chemistry</topic><topic>Organothiophosphorus Compounds - metabolism</topic><topic>Potassium Compounds - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Solano, Maria I.</creatorcontrib><creatorcontrib>Thomas, Jerry D.</creatorcontrib><creatorcontrib>Taylor, James T.</creatorcontrib><creatorcontrib>McGuire, Jeffrey M.</creatorcontrib><creatorcontrib>Jakubowski, Edward M.</creatorcontrib><creatorcontrib>Thomson, Sandra A.</creatorcontrib><creatorcontrib>Maggio, Vincent L.</creatorcontrib><creatorcontrib>Holland, Kerry E.</creatorcontrib><creatorcontrib>Smith, J. 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Richard</au><au>Capacio, Benedict</au><au>Woolfitt, Adrian R.</au><au>Ashley, David L.</au><au>Barr, John R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantification of Nerve Agent VX-Butyrylcholinesterase Adduct Biomarker from an Accidental Exposure</atitle><jtitle>Journal of analytical toxicology</jtitle><stitle>Journal of Analytical Toxicology</stitle><addtitle>Journal of Analytical Toxicology</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>32</volume><issue>1</issue><spage>68</spage><epage>72</epage><pages>68-72</pages><issn>0146-4760</issn><eissn>1945-2403</eissn><abstract>The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80nM, it can be calculated that inhibition levels of ≥ 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>18269796</pmid><doi>10.1093/jat/32.1.68</doi><tpages>5</tpages></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Biomarkers - analysis Biomarkers - blood Butyrylcholinesterase - chemistry Butyrylcholinesterase - metabolism Calibration Chemical Warfare Agents - analysis Chemical Warfare Agents - metabolism Cholinesterase Inhibitors - blood Cholinesterase Inhibitors - metabolism Environmental Exposure - analysis Environmental Monitoring - methods Fluorides - chemistry Gas Chromatography-Mass Spectrometry - methods Humans Organothiophosphorus Compounds - blood Organothiophosphorus Compounds - chemistry Organothiophosphorus Compounds - metabolism Potassium Compounds - chemistry |
title | Quantification of Nerve Agent VX-Butyrylcholinesterase Adduct Biomarker from an Accidental Exposure |
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