Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin
Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the pu...
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| Veröffentlicht in: | Journal of analytical toxicology 2018-11, Vol.42 (9), p.630-636 |
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| container_title | Journal of analytical toxicology |
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| creator | Isenberg, Samantha L Carter, Melissa D Miller, Michael A Noras, Aleksandra I Mojica, Mike A Carlsen, Sean T Bulathsinghala, Chinthaka P Thomas, Jerry D Johnson, Rudolph C |
| description | Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have |
| doi_str_mv | 10.1093/jat/bky040 |
| format | Article |
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Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay's time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.</description><identifier>ISSN: 0146-4760</identifier><identifier>EISSN: 1945-2403</identifier><identifier>DOI: 10.1093/jat/bky040</identifier><identifier>PMID: 29931062</identifier><language>eng</language><publisher>England</publisher><subject>Abrin - urine ; Alkaloids - poisoning ; Alkaloids - urine ; Biomarkers - urine ; Calibration ; Forensic Toxicology - methods ; Humans ; Indole Alkaloids - poisoning ; Indole Alkaloids - urine ; Limit of Detection ; Poisoning - urine ; Pyridones - poisoning ; Pyridones - urine ; Reproducibility of Results ; Ricin - urine ; Specimen Handling</subject><ispartof>Journal of analytical toxicology, 2018-11, Vol.42 (9), p.630-636</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-59188cf00b6177ab19be3d9175469e86112e3e925b2e336dad3a913d60ad16e33</citedby><cites>FETCH-LOGICAL-c378t-59188cf00b6177ab19be3d9175469e86112e3e925b2e336dad3a913d60ad16e33</cites><orcidid>0000-0002-8530-0795</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29931062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isenberg, Samantha L</creatorcontrib><creatorcontrib>Carter, Melissa D</creatorcontrib><creatorcontrib>Miller, Michael A</creatorcontrib><creatorcontrib>Noras, Aleksandra I</creatorcontrib><creatorcontrib>Mojica, Mike A</creatorcontrib><creatorcontrib>Carlsen, Sean T</creatorcontrib><creatorcontrib>Bulathsinghala, Chinthaka P</creatorcontrib><creatorcontrib>Thomas, Jerry D</creatorcontrib><creatorcontrib>Johnson, Rudolph C</creatorcontrib><title>Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin</title><title>Journal of analytical toxicology</title><addtitle>J Anal Toxicol</addtitle><description>Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay's time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.</description><subject>Abrin - urine</subject><subject>Alkaloids - poisoning</subject><subject>Alkaloids - urine</subject><subject>Biomarkers - urine</subject><subject>Calibration</subject><subject>Forensic Toxicology - methods</subject><subject>Humans</subject><subject>Indole Alkaloids - poisoning</subject><subject>Indole Alkaloids - urine</subject><subject>Limit of Detection</subject><subject>Poisoning - urine</subject><subject>Pyridones - poisoning</subject><subject>Pyridones - urine</subject><subject>Reproducibility of Results</subject><subject>Ricin - urine</subject><subject>Specimen Handling</subject><issn>0146-4760</issn><issn>1945-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkF1LwzAUhoMobk5v_AGSa6Eup2nTxgthjumEifPrOiRtqtnWdCStuH9vR3UqHHgP5-M5hxehUyAXQDgdLmQ9VMsNicge6gOP4iCMCN1HfQIRC6KEkR468n5BCLCU0UPUCzmnQFjYR_axkbY2hclkbSqLqwI_mcxYYzWWNscj5bapsXjalNLi-Ur6UmK1wdP5bBzcP7dxia9NVUq31M5vAZPPdeUbp3FddbBf0jE6KOTK65NvHaDXm8nLeBrMHm7vxqNZkNEkrYOYQ5pmBSGKQZJIBVxpmnNI4ohxnTKAUFPNw1i1Slkucyo50JwRmQNrSwN01XHXjSp1nmlbO7kSa2faPzeikkb871jzLt6qD8FCiJIYWsB5B8hc5b3TxW4XiNi6LlrXRed6O3z299pu9Mdm-gXye37R</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Isenberg, Samantha L</creator><creator>Carter, Melissa D</creator><creator>Miller, Michael A</creator><creator>Noras, Aleksandra I</creator><creator>Mojica, Mike A</creator><creator>Carlsen, Sean T</creator><creator>Bulathsinghala, Chinthaka P</creator><creator>Thomas, Jerry D</creator><creator>Johnson, Rudolph C</creator><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>5PM</scope><orcidid>https://orcid.org/0000-0002-8530-0795</orcidid></search><sort><creationdate>20181101</creationdate><title>Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin</title><author>Isenberg, Samantha L ; Carter, Melissa D ; Miller, Michael A ; Noras, Aleksandra I ; Mojica, Mike A ; Carlsen, Sean T ; Bulathsinghala, Chinthaka P ; Thomas, Jerry D ; Johnson, Rudolph C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-59188cf00b6177ab19be3d9175469e86112e3e925b2e336dad3a913d60ad16e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Abrin - urine</topic><topic>Alkaloids - poisoning</topic><topic>Alkaloids - urine</topic><topic>Biomarkers - urine</topic><topic>Calibration</topic><topic>Forensic Toxicology - methods</topic><topic>Humans</topic><topic>Indole Alkaloids - poisoning</topic><topic>Indole Alkaloids - urine</topic><topic>Limit of Detection</topic><topic>Poisoning - urine</topic><topic>Pyridones - poisoning</topic><topic>Pyridones - urine</topic><topic>Reproducibility of Results</topic><topic>Ricin - urine</topic><topic>Specimen Handling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isenberg, Samantha L</creatorcontrib><creatorcontrib>Carter, Melissa D</creatorcontrib><creatorcontrib>Miller, Michael A</creatorcontrib><creatorcontrib>Noras, Aleksandra I</creatorcontrib><creatorcontrib>Mojica, Mike A</creatorcontrib><creatorcontrib>Carlsen, Sean T</creatorcontrib><creatorcontrib>Bulathsinghala, Chinthaka P</creatorcontrib><creatorcontrib>Thomas, Jerry D</creatorcontrib><creatorcontrib>Johnson, Rudolph C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of analytical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isenberg, Samantha L</au><au>Carter, Melissa D</au><au>Miller, Michael A</au><au>Noras, Aleksandra I</au><au>Mojica, Mike A</au><au>Carlsen, Sean T</au><au>Bulathsinghala, Chinthaka P</au><au>Thomas, Jerry D</au><au>Johnson, Rudolph C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin</atitle><jtitle>Journal of analytical toxicology</jtitle><addtitle>J Anal Toxicol</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>42</volume><issue>9</issue><spage>630</spage><epage>636</epage><pages>630-636</pages><issn>0146-4760</issn><eissn>1945-2403</eissn><abstract>Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay's time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.</abstract><cop>England</cop><pmid>29931062</pmid><doi>10.1093/jat/bky040</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-8530-0795</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of analytical toxicology, 2018-11, Vol.42 (9), p.630-636 |
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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 | Abrin - urine Alkaloids - poisoning Alkaloids - urine Biomarkers - urine Calibration Forensic Toxicology - methods Humans Indole Alkaloids - poisoning Indole Alkaloids - urine Limit of Detection Poisoning - urine Pyridones - poisoning Pyridones - urine Reproducibility of Results Ricin - urine Specimen Handling |
| title | Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin |
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