128 results match your criteria soman cyclosarin

Release of protein-bound nerve agents by excess fluoride from whole blood: GC-MS/MS method development, validation, and application to a real-life denatured blood sample.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 15;1179:122693. Epub 2021 Apr 15.

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, D-80937 Munich, Germany. Electronic address:

In analogy to the fluoride-induced regeneration of butyrylcholinesterase (BChE) inhibited by nerve agents a method was developed and optimized for whole blood samples. Compared to the plasma method, regeneration grade was found to be higher for cyclosarin (GF), i-butylsarin from VR, and n-butylsarin from CVX, but lower for sarin (GB), fluorotabun from tabun (GA), and ethylsarin from VX. Regeneration grade of soman (GD) is the same for both matrices because it is released from serum albumin and not from cholinesterases. Read More

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Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6.

Chem Res Toxicol 2021 Mar 4;34(3):804-816. Epub 2021 Feb 4.

United States Army Futures Command, Combat Capabilities Development Command, Chemical Biological Center, Chemcial Sciences Division, Agent Chemistry Branch, Aberdeen Proving Ground, Aberdeen, Maryland 21010-5424, United States.

The recent use of organophosphate nerve agents in Syria, Malaysia, Russia, and the United Kingdom has reinforced the potential threat of their intentional release. These agents act through their ability to inhibit human acetylcholinesterase (hAChE; E.C. Read More

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Improving Quantification of tabun, sarin, soman, cyclosarin, and sulfur mustard by focusing agents: A field portable gas chromatography-mass spectrometry study.

J Chromatogr A 2021 Jan 13;1636:461784. Epub 2020 Dec 13.

Hazardous Materials Research Center (HMRC), Battelle Columbus Laboratories, Battelle Memorial Institute, Columbus, OH, USA.

Commercial gas chromatograph-mass spectrometers, one of which being Inficon's HAPSITE® ER, have demonstrated chemical detection and identification of nerve agents (G-series) and blistering agents (mustard gas) in the field; however most analyses relies on self-contained or external calibration that inherently drifts over time. We describe an analytical approach that uses target-based thermal desorption standards, called focusing agents, to accurately calculate concentrations of chemical warfare agents that are analyzed by gas chromatograph-mass spectrometry. Here, we provide relative response factors of focusing agents (2-chloroethyl ethyl sulfide, diisopropyl fluorophosphate, diethyl methylphosphonate, diethyl malonate, methyl salicylate, and dichlorvos) that are used to quantify concentrations of tabun, sarin, soman, cyclosarin and sulfur mustard loaded on thermal desorption tubes (Tenax® TA). Read More

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January 2021

Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures.

Neuropharmacology 2020 12 6;181:108298. Epub 2020 Sep 6.

Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814, USA; Department of Psychiatry, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. Electronic address:

Nerve agents are organophosphorus acetylcholinesterase inhibitors. Acute exposure to nerve agents can cause rapid death. In this review, we summarize the history of nerve agent development and use in warfare, the mechanisms by which these agents cause death or long-term brain damage, and the treatments for preventing death or long-term morbidity. Read More

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December 2020

Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice - a comparison with oxime-based treatment.

Toxicol Mech Methods 2020 Nov 20;30(9):703-710. Epub 2020 Sep 20.

Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (DSTL), Salisbury, United Kingdom.

Therapeutic efficacy of antidotal treatment of acute poisoning by nerve agents is generally assessed by the evaluation of LD values of nerve agents over 24 h following poisoning without or with a single administration of antidotal treatment. In this study, LD values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated poisoning were evaluated in mice for two experimental end points - 6 h and 24 h. While the efficacy of atropine or oxime-based antidotal treatment was the same regardless of the experimental end point, the therapeutic efficacy of all three newly developed bispyridinium non-oxime compounds (MB408, MB442, and MB444) was mostly slightly higher at the 6 h end point compared to the 24 h end point, although the therapeutic efficacy of MB compounds was not superior to oxime-based antidotal treatment. Read More

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November 2020

In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase.

Molecules 2020 Jul 2;25(13). Epub 2020 Jul 2.

Bundeswehr Institute of Pharmacology and Toxicology, D-80937 Munich, Germany.

The implementation of the Chemical Weapons Convention (CWC) in 1997 was a milestone in the prohibition of chemical warfare agents (CWA). Yet, the repeated use of CWA underlines the ongoing threat to the population. Organophosphorus (OP) nerve agents still represent the most toxic CWA subgroup. Read More

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Structural and kinetic evidence of aging after organophosphate inhibition of human Cathepsin A.

Biochem Pharmacol 2020 07 17;177:113980. Epub 2020 Apr 17.

U.S. Naval Research Laboratory, 4555 Overlook Ave., Washington, DC 20375, United States. Electronic address:

Human Cathepsin A (CatA) is a lysosomal serine carboxypeptidase of the renin-angiotensin system (RAS) and is structurally similar to acetylcholinesterase (AChE). CatA can remove the C-terminal amino acids of endothelin I, angiotensin I, Substance P, oxytocin, and bradykinin, and can deamidate neurokinin A. Proteomic studies identified CatA and its homologue, SCPEP1, as potential targets of organophosphates (OP). Read More

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Structural and Functional Characterization of New SsoPox Variant Points to the Dimer Interface as a Driver for the Increase in Promiscuous Paraoxonase Activity.

Int J Mol Sci 2020 Mar 1;21(5). Epub 2020 Mar 1.

Institute of Biochemistry and Cell Biology, CNR, 80131 Naples, Italy.

Increasing attention is more and more directed toward the thermostable Phosphotriesterase-Like-Lactonase (PLL) family of enzymes, for the efficient and reliable decontamination of toxic nerve agents. In the present study, the DNA Staggered Extension Process (StEP) technique was utilized to obtain new variants of PLL enzymes. Divergent homologous genes encoding PLL enzymes were utilized as templates for gene recombination and yielded a new variant of SsoPox from . Read More

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Detection of Chemical Weapon Nerve Agents in Bone by Liquid Chromatography-Mass Spectrometry.

J Anal Toxicol 2020 May;44(4):391-401

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, 4800 SW 35th Drive, Gainesville, FL 32608.

A recently proposed model for the incorporation of xenobiotics of forensic interest into the human skeleton suggests nerve agent metabolites may incorporate into bone at relatively elevated concentrations based on their unique chemical properties. To test the hypothesis that nerve agent metabolites interact with bone, methods for the extraction, isolation and semi-quantitative detection of nerve agent metabolites (MPA, EMPA, IMPA, iBuMPA, CMPA and PMPA, corresponding to the nerve agents VX, Russian VX, sarin, cyclosarin and soman, respectively) from osseous tissue were developed using liquid chromatography-mass spectrometry with both quadrupole time-of-flight and triple quadrupole (QqQ) instruments. The optimized methods were validated on the QqQ instrument. Read More

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Gene therapy delivering a paraoxonase 1 variant offers long-term prophylactic protection against nerve agents in mice.

Sci Transl Med 2020 01;12(527)

Medical Toxicology Research Division, Biochemistry & Physiology Department, Agent Mitigation, United States Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA.

Chemical warfare nerve agents are organophosphorus chemical compounds that induce cholinergic crisis, leaving little or no time for medical intervention to prevent death. The current chemical treatment regimen may prevent death but does not prevent postexposure complications such as brain damage and permanent behavioral abnormalities. In the present study, we have demonstrated an adeno-associated virus 8 (AAV8)-mediated paraoxonase 1 variant IF-11 (PON1-IF11) gene therapy that offers asymptomatic prophylactic protection to mice against multiple lethal doses of G-type chemical warfare nerve agents, namely, tabun, sarin, cyclosarin, and soman, for up to 5 months in mice. Read More

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January 2020

Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure.

Rapid Commun Mass Spectrom 2020 May;34(9):e8721

State Key Laboratory of NBC Protection for Civilians, Beijing, 102205, China.

Rationale: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. Read More

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A catalytic bioscavenger with improved stability and reduced susceptibility to oxidation for treatment of acute poisoning with neurotoxic organophosphorus compounds.

Toxicol Lett 2020 Mar 28;321:138-145. Epub 2019 Dec 28.

Lehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany. Electronic address:

Organophosphorus (OP) nerve agents pose a severe toxicological threat, both after dissemination in military conflicts and by terrorists. Hydrolytic enzymes, which may be administered into the blood stream of victims by injection and can decompose the circulating nerve agent into non-toxic metabolites in vivo, could offer a treatment. Indeed, for the phosphotriesterase found in the bacterium Brevundimonas diminuta (BdPTE), engineered versions with improved catalytic efficiencies have been described; yet, their biochemical stabilities are insufficient for therapeutic use. Read More

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A Strip Biosensor with Guinea Green B and Fuchsin Basic Color Indicators on a Glass Nanofiber Carrier for the Cholinesterase Detection of Nerve Agents.

ACS Omega 2019 Dec 2;4(25):20978-20986. Epub 2019 Dec 2.

Oritest spol. s.r.o., Nábřežní 90/4, 150 00 Prague, Czech Republic.

This paper deals with the innovation of the Czech colorimetric biosensor Detehit designed for the simple, fast, and sensitive detection of nerve agents. The innovation is based on the use of an indicator consisting of a mixture of two triphenylmethane dyes, Guinea green B and a basic fuchsin, on a glass nanofiber filter paper carrier. The advantage of this solution is the blue-red color transition, which is much more visible than the white-yellow transition of other Detehit biosensors. Read More

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December 2019

A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents.

Protein Eng Des Sel 2019 12;32(4):169-174

Department of Biomolecular Sciences, Weizmann Institute of Science, Herzl st. 234, Rehovot 7610001, Israel.

Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Read More

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December 2019

Methylation protocol for the retrospective detection of isopropyl-, pinacolyl- and cyclohexylmethylphosphonic acids, indicative markers for the nerve agents sarin, soman and cyclosarin, at low levels in soils using EI-GC-MS.

Sci Total Environ 2019 Sep 16;683:175-184. Epub 2019 May 16.

Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, L-091, Livermore, CA 94550, USA; Forensic Science Center, Lawrence Livermore National Laboratory, 7000 East Avenue, L-091, Livermore, CA 94550, USA.

A practical and efficient protocol for the derivatization and detection by GC-EI-MS of isopropyl-, pinacolyl- and cyclohexylmethylphosphonic acids, key diagnostic degradation products of the nerve agents sarin, soman and cyclosarin respectively, in six different types of soil matrices is presented. The method involves the in situ conversion of the phosphonic acids to their respective methyl esters using trimethyloxonium tetrafluoroborate when present in the soils at low levels (10 μg g) without any prior extractions or soil preparation. The soils employed in our study were Nebraska EPA soil, Georgia soil, silt, Virginia type A soil, regular sand and Ottawa sand and were chosen for their vast differences in composition and physical features. Read More

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September 2019

Comparative effects of scopolamine and phencynonate on organophosphorus nerve agent-induced seizure activity, neuropathology and lethality.

Toxicol Mech Methods 2019 Jun 22;29(5):322-333. Epub 2019 Jan 22.

a Medical Toxicology Research Division , US Army Medical Research Institute of Chemical Defense , Edgewood , MD , USA.

The efficacy of anticonvulsant therapies to stop seizure activities following organophosphorus nerve agents (NAs) has been documented as being time-dependent. We utilized the guinea pig NA-seizure model to compare the effectiveness of phencynonate (PCH) and scopolamine (SCP) when given at the early (at time of seizure onset) or late (40 min after seizure onset) phase of seizure progression. PCH possesses both anticholinergic and anti-NMDA activities, while SCP is a purely anti-muscarinic compound. Read More

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A Novel Potential Biomarker on Y263 Site in Human Serum Albumin Poisoned by Six Nerve Agents.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Jan 9;1104:168-175. Epub 2018 Nov 9.

State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China. Electronic address:

Albumin is a new biomarker of organophosphorus compounds (OPs) and nerve agents (OPNAs) for retrospective verification. Recent studies on OPs adducts show that amino acid residues can covalently bind to OPs and OPNAs. In this article, after being incubated with soman, sarin, cyclosarin, VX, ethyl tabun, and propyl tabun, human serum albumin (HSA) is analyzed by quadrupole-Orbitrap mass spectrometer (Q Exactive LC-MS/MS). Read More

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January 2019

The Application of a Single-Column GC-MS-MS Method for the Rapid Analysis of Chemical Warfare Agents and Breakdown Products.

J Anal Toxicol 2019 Apr;43(3):179-187

US Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Road, MD, USA.

The development of one comprehensive gas chromatographic-triple quadrupole mass spectrometric (GC-MS-MS) method for the analysis of nerve agents and their breakdown products can pose a challenge due to significant differences in analyte volatility. Nerve agent breakdown products typically have a low volatility, requiring a derivatization step prior to analysis by gas chromatography (GC). However, nerve agent parent compounds are generally more volatile, which eliminates the need for derivatization and allows for direct analysis. Read More

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Aqueous extraction followed by derivatization and liquid chromatography-mass spectrometry analysis: A unique strategy for trace detection and identification of G-nerve agents in environmental matrices.

J Chromatogr A 2018 Nov 27;1577:24-30. Epub 2018 Sep 27.

Department of Analytical Chemistry, Israel Institute for Biological Research (IIBR), P.O. Box 19, Ness Ziona, Israel.

A highly sensitive method for the detection and identification of sarin (GB), soman (GD) and cyclosarin (GF) chemical warfare agents (CWAs) in environmental outdoor and indoor matrices such as soil, asphalt, linoleum, formica, concrete and cloth was developed. The method incorporates derivatization of the G-type nerve agent extracts with 2-[(dimethylamino)methyl]phenol (2-DMAMP), followed by LC-ESI(+)-MS/MS analysis. Four LC-amenable extraction solvents were explored in terms of their extraction efficiency and the reaction rate of the derivatizing agent. Read More

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November 2018

Automated Design of Efficient and Functionally Diverse Enzyme Repertoires.

Mol Cell 2018 10 27;72(1):178-186.e5. Epub 2018 Sep 27.

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address:

Substantial improvements in enzyme activity demand multiple mutations at spatially proximal positions in the active site. Such mutations, however, often exhibit unpredictable epistatic (non-additive) effects on activity. Here we describe FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations. Read More

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October 2018

Modified Biosensor for Cholinesterase Inhibitors with Guinea Green B as the Color Indicator.

Biosensors (Basel) 2018 Sep 4;8(3). Epub 2018 Sep 4.

National Institute for Nuclear, Chemical and Biological Protection, Kamenná 71, 262 31 Milín, Czech Republic.

Colorimetric biosensors of cholinesterase inhibitors are ideal for fast, reliable, and very simple detection of agents in air, in water, and on surfaces. This paper describes an innovation of the Czech Detehit biosensor, which is based on a biochemical enzymatic reaction visualized by using Ellman's reagent as a chromogenic indicator. The modification basically consists of a much more distinct color response of the biosensor, attained through optimization of the reaction system by using Guinea Green B as the indicator. Read More

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September 2018

Investigation of dried blood sampling with liquid chromatography tandem mass spectrometry to confirm human exposure to nerve agents.

Anal Chim Acta 2018 Nov 20;1033:100-107. Epub 2018 Jun 20.

Emergency Response Branch, Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA, 30341, USA.

A method was developed to detect and quantify organophosphate nerve agent (OPNA) metabolites in dried blood samples. Dried blood spots (DBS) and microsampling devices are alternatives to traditional blood draws, allowing for safe handling, extended stability, reduced shipping costs, and potential self-sampling. DBS and microsamplers were evaluated for precision, accuracy, sensitivity, matrix effects, and extraction recovery following collection of whole blood containing five OPNA metabolites. Read More

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November 2018

Acute and long-term consequences of exposure to organophosphate nerve agents in humans.

Epilepsia 2018 10 29;59 Suppl 2:92-99. Epub 2018 Aug 29.

Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Nerve agents are organophosphate (OP) compounds and among the most powerful poisons known to man. A terrorist attack on civilian or military populations causing mass casualties is a real threat. The OP nerve agents include soman, sarin, cyclosarin, tabun, and VX. Read More

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October 2018

Dry Blood Spot sample collection for post-exposure monitoring of chemical warfare agents - In vivo determination of phosphonic acids using LC-MS/MS.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Sep 19;1093-1094:60-65. Epub 2018 Jun 19.

Israel Institute for Biological Research (IIBR), P.O.B. 19, Ness Ziona, Israel.

Phosphonic acids are the direct and immediate metabolites of organophosphorus chemical warfare agents (OP-CWAs). Accordingly, their detection serves for evaluating exposure to OP-CWAs in a terror or war scenario. After exposure, phosphonic acids are present in the blood; however, blood drawing must be carried out by medical personnel, hence the number of samples that can be drawn in a mass-casualty event is limited. Read More

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September 2018

Theoretical Studies Applied to the Evaluation of the DFPase Bioremediation Potential against Chemical Warfare Agents Intoxication.

Int J Mol Sci 2018 Apr 23;19(4). Epub 2018 Apr 23.

Center for Basic and Applied Research, Faculty of Informatics and Management, University Hradec Kralove, 50003 Hradec Kralove, Czech Republic.

Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. Read More

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Metal-Organic Framework Modified Glass Substrate for Analysis of Highly Volatile Chemical Warfare Agents by Paper Spray Mass Spectrometry.

ACS Appl Mater Interfaces 2018 Mar 21;10(9):8359-8365. Epub 2018 Feb 21.

Research and Technology Directorate , U.S. Army Edgewood Chemical Biological Center (ECBC) , Aberdeen Proving Ground , Maryland 21010 , United States.

Paper spray mass spectrometry has been shown to successfully analyze chemical warfare agent (CWA) simulants. However, due to the volatility differences between the simulants and real G-series (i.e. Read More

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Determination of trace amounts of G-type nerve agents in aqueous samples utilizing "in vial" instantaneous derivatization and liquid chromatography-tandem mass spectrometry.

J Chromatogr A 2017 Aug 4;1512:71-77. Epub 2017 Jul 4.

Department of Analytical Chemistry, Israel Institute for Biological Research (IIBR), P.O.B. 19, Ness Ziona, Israel.

A methodology for sensitive determination of sarin (GB), soman (GD) and cyclosarin (GF) chemical warfare agents in aqueous media was developed. The method incorporates direct derivatization with 2-[(dimethylamino)methyl]phenol (2-DMAMP), a commercially available, water-soluble reagent, followed by LC-ESI-MS/MS analysis in the positive ion mode. Five derivatization agents were characterized for their MS/MS fragmentation pattern, and their reaction time, temperature and derivatization-reagent amount were optimized. Read More

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Coupling Activity-Based Detection, Target Amplification, Colorimetric and Fluorometric Signal Amplification, for Quantitative Chemosensing of Fluoride Generated from Nerve Agents.

Chemistry 2017 Mar 15;23(16):3903-3909. Epub 2017 Feb 15.

Department of Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.

The G-class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Read More

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Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

Toxicol Lett 2016 Nov 14;262:12-16. Epub 2016 Sep 14.

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e. Read More

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November 2016

Novel bifunctional hybrid small molecule scavengers for mitigating nerve agents toxicity.

Chem Biol Interact 2016 Nov 27;259(Pt B):187-204. Epub 2016 Apr 27.

Department of Pharmacology, Division of Medicinal Chemistry, Israel Institute for Biological Research, PO Box 19, Ness Ziona 74100, Israel. Electronic address:

The antidotal treatment of organophosphates (OP) nerve agents (NA) poisoning is based on anticholinergics (e.g. atropine) combined with oxime reactivators (e. Read More

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November 2016