Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC–MS/MS and LC–MS/MS
The present study was intended to develop suitable methods for unambiguous identification and determination of ethyl (1-(diethylamino)ethylidene) phosphoramidofluoridate (known as A234-Novichok) biomarkers in urine and plasma samples. Multiple biomarkers were investigated for the first time, to veri...
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description | The present study was intended to develop suitable methods for unambiguous identification and determination of ethyl (1-(diethylamino)ethylidene) phosphoramidofluoridate (known as A234-Novichok) biomarkers in urine and plasma samples. Multiple biomarkers were investigated for the first time, to verify intoxication by the A234-Novichok agent, using sensitive and accurate techniques including gas and liquid chromatography-tandem mass spectrometry (GC–MS/MS and LC–MS/MS). Like other nerve agents, in biological matrices, the A234-Novichok agent reacts with several proteins to form related adducts. Considering this, two different protein adduct biomarkers in blood samples were analyzed, and the regenerated A234 was determined. Two-dimensional chromatography and solid-phase extraction techniques were employed for blood sample preparation. Limits of detection for butyrylcholinesterase (BChE) adduct, the regenerated A234, and albumin covalent adduct were determined and reported as 1, 1, and 10 ng mL
−1
, while the related calibration curves were linear within the range of 2–100, 2–100, and 15–100 ng mL
−1
, respectively. The detection limit and linear range for the intact agent in the urine sample were determined as 0.1 and 1–100 ng mL
−1
, respectively. Since A234 and some other Novichok chemicals have been added to the Schedule 1 of the Chemical Weapons Convention (CWC), Annex on Chemicals, after UK incidents, the analytical methods developed in this work might be used for verification purposes, as well as OPCW Biomedical Proficiency Tests.
Graphical abstract |
doi_str_mv | 10.1007/s00216-022-03964-1 |
format | Article |
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−1
, while the related calibration curves were linear within the range of 2–100, 2–100, and 15–100 ng mL
−1
, respectively. The detection limit and linear range for the intact agent in the urine sample were determined as 0.1 and 1–100 ng mL
−1
, respectively. Since A234 and some other Novichok chemicals have been added to the Schedule 1 of the Chemical Weapons Convention (CWC), Annex on Chemicals, after UK incidents, the analytical methods developed in this work might be used for verification purposes, as well as OPCW Biomedical Proficiency Tests.
Graphical abstract</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-022-03964-1</identifier><identifier>PMID: 35190842</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adducts ; Albumins ; Analytical Chemistry ; Biochemistry ; Biological markers ; Biomarkers ; Blood ; Butyrylcholinesterase ; Characterization and Evaluation of Materials ; Chemical properties ; Chemical weapons ; Chemistry ; Chemistry and Materials Science ; Chromatography ; Chromatography, Liquid - methods ; Food Science ; Gas chromatography ; Gas Chromatography-Mass Spectrometry ; Identification and classification ; Intoxication ; Laboratory Medicine ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Methods ; Monitoring/Environmental Analysis ; Nerve agents ; Nerve Agents - analysis ; Nerves ; Organophosphates ; Protein adducts ; Proteins ; Research Paper ; Sample preparation ; Solid phases ; Tandem Mass Spectrometry - methods</subject><ispartof>Analytical and bioanalytical chemistry, 2022-05, Vol.414 (11), p.3429-3442</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>COPYRIGHT 2022 Springer</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-4e690ab7411688f0c0941bc14c5b260da8109cae7e1e7cb473cd647a895df0d83</citedby><cites>FETCH-LOGICAL-c508t-4e690ab7411688f0c0941bc14c5b260da8109cae7e1e7cb473cd647a895df0d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00216-022-03964-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-022-03964-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35190842$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mirbabaei, Fatemeh</creatorcontrib><creatorcontrib>Mohammad-Khah, Ali</creatorcontrib><creatorcontrib>Naseri, Mohammad Taghi</creatorcontrib><creatorcontrib>Babri, Mehran</creatorcontrib><creatorcontrib>Faraz, Sajjad Mousavi</creatorcontrib><creatorcontrib>Hosseini, Seyyed Esmaeil</creatorcontrib><creatorcontrib>Ashrafi, Davood</creatorcontrib><title>Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC–MS/MS and LC–MS/MS</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>The present study was intended to develop suitable methods for unambiguous identification and determination of ethyl (1-(diethylamino)ethylidene) phosphoramidofluoridate (known as A234-Novichok) biomarkers in urine and plasma samples. Multiple biomarkers were investigated for the first time, to verify intoxication by the A234-Novichok agent, using sensitive and accurate techniques including gas and liquid chromatography-tandem mass spectrometry (GC–MS/MS and LC–MS/MS). Like other nerve agents, in biological matrices, the A234-Novichok agent reacts with several proteins to form related adducts. Considering this, two different protein adduct biomarkers in blood samples were analyzed, and the regenerated A234 was determined. Two-dimensional chromatography and solid-phase extraction techniques were employed for blood sample preparation. Limits of detection for butyrylcholinesterase (BChE) adduct, the regenerated A234, and albumin covalent adduct were determined and reported as 1, 1, and 10 ng mL
−1
, while the related calibration curves were linear within the range of 2–100, 2–100, and 15–100 ng mL
−1
, respectively. The detection limit and linear range for the intact agent in the urine sample were determined as 0.1 and 1–100 ng mL
−1
, respectively. Since A234 and some other Novichok chemicals have been added to the Schedule 1 of the Chemical Weapons Convention (CWC), Annex on Chemicals, after UK incidents, the analytical methods developed in this work might be used for verification purposes, as well as OPCW Biomedical Proficiency Tests.
Graphical abstract</description><subject>Adducts</subject><subject>Albumins</subject><subject>Analytical Chemistry</subject><subject>Biochemistry</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Butyrylcholinesterase</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemical properties</subject><subject>Chemical weapons</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chromatography</subject><subject>Chromatography, Liquid - methods</subject><subject>Food Science</subject><subject>Gas chromatography</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>Identification and classification</subject><subject>Intoxication</subject><subject>Laboratory Medicine</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Methods</subject><subject>Monitoring/Environmental Analysis</subject><subject>Nerve agents</subject><subject>Nerve Agents - analysis</subject><subject>Nerves</subject><subject>Organophosphates</subject><subject>Protein adducts</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Sample preparation</subject><subject>Solid phases</subject><subject>Tandem Mass Spectrometry - methods</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFu1DAQhiMEoqXwAhyQJS5c0o4dx3GOq1UpSFs4lJ4tx54Et4ld7KQSN66ceUOeBG-3bAVCyAd7xt__a-y_KF5SOKYAzUkCYFSUwFgJVSt4SR8Vh1RQWTJRw-P9mbOD4llKVwC0llQ8LQ6qmrYgOTssvl96PXVuWMKSiLPoZ9c7o2cXPNHeEoszxsn5XSf0ZMUqXn4It858DtfEY7xFooesI50Lk47XGLOR31ZjGLLVSPpxcTaRJTk_kLP1z28_zi9Ozi_u_Df78nnxpNdjwhf3-1Fx-fb00_pdufl49n692pSmBjmXHEULums4pULKHgy0nHaGclN3TIDVkkJrNDZIsTEdbypjBW-0bGvbg5XVUfFm53sTw5cF06wmlwyOo_aYP0ExUVEpOG9YRl__hV6FJfo8XaZqxqGVLX-gBj2icr4Pc9Rma6pWDVBgbVXXmTr-B5WXxcmZ4LF3uf-HgO0EJoaUIvbqJrr8wV8VBbXNX-3yVzl_dZe_oln06n7ipZvQ7iW_A89AtQNSvvIDxocn_cf2F9bjuoA</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Mirbabaei, Fatemeh</creator><creator>Mohammad-Khah, Ali</creator><creator>Naseri, Mohammad Taghi</creator><creator>Babri, Mehran</creator><creator>Faraz, Sajjad Mousavi</creator><creator>Hosseini, Seyyed Esmaeil</creator><creator>Ashrafi, Davood</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature 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>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20220501</creationdate><title>Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC–MS/MS and LC–MS/MS</title><author>Mirbabaei, Fatemeh ; Mohammad-Khah, Ali ; Naseri, Mohammad Taghi ; Babri, Mehran ; Faraz, Sajjad Mousavi ; Hosseini, Seyyed Esmaeil ; Ashrafi, Davood</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-4e690ab7411688f0c0941bc14c5b260da8109cae7e1e7cb473cd647a895df0d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adducts</topic><topic>Albumins</topic><topic>Analytical Chemistry</topic><topic>Biochemistry</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Butyrylcholinesterase</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemical properties</topic><topic>Chemical weapons</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chromatography</topic><topic>Chromatography, Liquid - methods</topic><topic>Food Science</topic><topic>Gas chromatography</topic><topic>Gas Chromatography-Mass Spectrometry</topic><topic>Identification and classification</topic><topic>Intoxication</topic><topic>Laboratory Medicine</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Methods</topic><topic>Monitoring/Environmental Analysis</topic><topic>Nerve agents</topic><topic>Nerve Agents - analysis</topic><topic>Nerves</topic><topic>Organophosphates</topic><topic>Protein adducts</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>Sample preparation</topic><topic>Solid phases</topic><topic>Tandem Mass Spectrometry - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mirbabaei, Fatemeh</creatorcontrib><creatorcontrib>Mohammad-Khah, Ali</creatorcontrib><creatorcontrib>Naseri, Mohammad Taghi</creatorcontrib><creatorcontrib>Babri, Mehran</creatorcontrib><creatorcontrib>Faraz, Sajjad Mousavi</creatorcontrib><creatorcontrib>Hosseini, Seyyed Esmaeil</creatorcontrib><creatorcontrib>Ashrafi, Davood</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Biological Sciences</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical and bioanalytical chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mirbabaei, Fatemeh</au><au>Mohammad-Khah, Ali</au><au>Naseri, Mohammad Taghi</au><au>Babri, Mehran</au><au>Faraz, Sajjad Mousavi</au><au>Hosseini, Seyyed Esmaeil</au><au>Ashrafi, Davood</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC–MS/MS and LC–MS/MS</atitle><jtitle>Analytical and bioanalytical chemistry</jtitle><stitle>Anal Bioanal Chem</stitle><addtitle>Anal Bioanal Chem</addtitle><date>2022-05-01</date><risdate>2022</risdate><volume>414</volume><issue>11</issue><spage>3429</spage><epage>3442</epage><pages>3429-3442</pages><issn>1618-2642</issn><eissn>1618-2650</eissn><abstract>The present study was intended to develop suitable methods for unambiguous identification and determination of ethyl (1-(diethylamino)ethylidene) phosphoramidofluoridate (known as A234-Novichok) biomarkers in urine and plasma samples. Multiple biomarkers were investigated for the first time, to verify intoxication by the A234-Novichok agent, using sensitive and accurate techniques including gas and liquid chromatography-tandem mass spectrometry (GC–MS/MS and LC–MS/MS). Like other nerve agents, in biological matrices, the A234-Novichok agent reacts with several proteins to form related adducts. Considering this, two different protein adduct biomarkers in blood samples were analyzed, and the regenerated A234 was determined. Two-dimensional chromatography and solid-phase extraction techniques were employed for blood sample preparation. Limits of detection for butyrylcholinesterase (BChE) adduct, the regenerated A234, and albumin covalent adduct were determined and reported as 1, 1, and 10 ng mL
−1
, while the related calibration curves were linear within the range of 2–100, 2–100, and 15–100 ng mL
−1
, respectively. The detection limit and linear range for the intact agent in the urine sample were determined as 0.1 and 1–100 ng mL
−1
, respectively. Since A234 and some other Novichok chemicals have been added to the Schedule 1 of the Chemical Weapons Convention (CWC), Annex on Chemicals, after UK incidents, the analytical methods developed in this work might be used for verification purposes, as well as OPCW Biomedical Proficiency Tests.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35190842</pmid><doi>10.1007/s00216-022-03964-1</doi><tpages>14</tpages></addata></record> |
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subjects | Adducts Albumins Analytical Chemistry Biochemistry Biological markers Biomarkers Blood Butyrylcholinesterase Characterization and Evaluation of Materials Chemical properties Chemical weapons Chemistry Chemistry and Materials Science Chromatography Chromatography, Liquid - methods Food Science Gas chromatography Gas Chromatography-Mass Spectrometry Identification and classification Intoxication Laboratory Medicine Liquid chromatography Mass spectrometry Mass spectroscopy Methods Monitoring/Environmental Analysis Nerve agents Nerve Agents - analysis Nerves Organophosphates Protein adducts Proteins Research Paper Sample preparation Solid phases Tandem Mass Spectrometry - methods |
title | Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC–MS/MS and LC–MS/MS |
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