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Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS

Ricin, a protein derived from the seeds of the castor bean plant (Ricinus communis), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread availability of ricin, its ease of extraction and its extreme toxicity make it an ideal agent for bioterrorism and se...

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Detalles Bibliográficos
Autores principales: Feldberg, Liron, Elhanany, Eytan, Laskar, Orly, Schuster, Ofir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911523/
https://www.ncbi.nlm.nih.gov/pubmed/33499033
http://dx.doi.org/10.3390/toxins13020079
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author Feldberg, Liron
Elhanany, Eytan
Laskar, Orly
Schuster, Ofir
author_facet Feldberg, Liron
Elhanany, Eytan
Laskar, Orly
Schuster, Ofir
author_sort Feldberg, Liron
collection PubMed
description Ricin, a protein derived from the seeds of the castor bean plant (Ricinus communis), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread availability of ricin, its ease of extraction and its extreme toxicity make it an ideal agent for bioterrorism and self-poisoning. Thus, a rapid, sensitive and reliable method for ricin identification in clinical samples is required for applying appropriate and timely medical intervention. However, this goal is challenging due to the low predicted toxin concentrations in bio-fluids, accompanied by significantly high matrix interferences. Here we report the applicability of a sensitive, selective, rapid, simple and antibody-independent assay for the identification of ricin in body fluids using mass spectrometry (MS). The assay involves lectin affinity capturing of ricin by easy-to-use commercial lactose–agarose (LA) beads, following by tryptic digestion and selected marker identification using targeted LC–MS/MS (Multiple Reaction Monitoring) analysis. This enables ricin identification down to 5 ng/mL in serum samples in 2.5 h. To validate the assay, twenty-four diverse naive- or ricin-spiked serum samples were evaluated, and both precision and accuracy were determined. A real-life test of the assay was successfully executed in a challenging clinical scenario, where the toxin was identified in an abdominal fluid sample taken 72 h post self-injection of castor beans extraction in an eventual suicide case. This demonstrates both the high sensitivity of this assay and the extended identification time window, compared to similar events that were previously documented. This method developed for ricin identification in clinical samples has the potential to be applied to the identification of other lectin toxins.
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spelling pubmed-79115232021-02-28 Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS Feldberg, Liron Elhanany, Eytan Laskar, Orly Schuster, Ofir Toxins (Basel) Article Ricin, a protein derived from the seeds of the castor bean plant (Ricinus communis), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread availability of ricin, its ease of extraction and its extreme toxicity make it an ideal agent for bioterrorism and self-poisoning. Thus, a rapid, sensitive and reliable method for ricin identification in clinical samples is required for applying appropriate and timely medical intervention. However, this goal is challenging due to the low predicted toxin concentrations in bio-fluids, accompanied by significantly high matrix interferences. Here we report the applicability of a sensitive, selective, rapid, simple and antibody-independent assay for the identification of ricin in body fluids using mass spectrometry (MS). The assay involves lectin affinity capturing of ricin by easy-to-use commercial lactose–agarose (LA) beads, following by tryptic digestion and selected marker identification using targeted LC–MS/MS (Multiple Reaction Monitoring) analysis. This enables ricin identification down to 5 ng/mL in serum samples in 2.5 h. To validate the assay, twenty-four diverse naive- or ricin-spiked serum samples were evaluated, and both precision and accuracy were determined. A real-life test of the assay was successfully executed in a challenging clinical scenario, where the toxin was identified in an abdominal fluid sample taken 72 h post self-injection of castor beans extraction in an eventual suicide case. This demonstrates both the high sensitivity of this assay and the extended identification time window, compared to similar events that were previously documented. This method developed for ricin identification in clinical samples has the potential to be applied to the identification of other lectin toxins. MDPI 2021-01-22 /pmc/articles/PMC7911523/ /pubmed/33499033 http://dx.doi.org/10.3390/toxins13020079 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Feldberg, Liron
Elhanany, Eytan
Laskar, Orly
Schuster, Ofir
Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title_full Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title_fullStr Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title_full_unstemmed Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title_short Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC–MS/MS
title_sort rapid, sensitive and reliable ricin identification in serum samples using lc–ms/ms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911523/
https://www.ncbi.nlm.nih.gov/pubmed/33499033
http://dx.doi.org/10.3390/toxins13020079
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