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Most of the precursors and/or degradation products related to the Chemical Weapons Convention (CWC) are polar. Identification of these molecules in environmental samples provides clues regarding the alleged usage and/or synthesis of the parent toxic chemicals. Such polar compounds need to be derivatized in order to analyze them by gas chromatography–mass spectrometry (GC–MS). In this study, we developed a new derivatizing reagent, para -tolyl isocyanate (PTI), for derivatization of polar CWC-related compounds. The PTI reagent selectively derivatizes the –OH and/or−SH functional groups with high efficiency, but does not react with carboxylic acid (−COOH) or phosphonic acid (−(O)P(OH) 2 ) groups. The PTI derivatives of dialkyl aminoethanols, dialkyl aminoethanol- N -oxides, and 3-quinuclidinol were successfully eluted through GC, and their electron ionization (EI) mass spectra were distinct and provided the structure information by which the isomeric compounds can be easily distinguished. We also calculated the GC-retention index values that can be used for further confirmation of the target compounds. All the studied PTI derivatives can be analyzed by EI-MS with direct insertion probe and/or by direct electrospray ionization mass spectrometry (ESI-MS) together with the MS–MS data; both sets of data provide full structure information. The PTI reagent was found to be better in some respects than the conventional bistrimethylsilyl trifluoroacetamide (BSTFA), a trimethyl silylating reagent. The PTI reagent is commercially available, and the PTI derivatives are highly stable for months and are not sensitive to moisture. The applicability of the PTI derivatization for trace-level determination of the target CWC-related polar compounds in environmental matrices and in human plasma samples is also evaluated. Fig. a ᅟ

2014 marks the centennial of the outbreak of World War I-the first war that saw the large-scale use of chemical weapons. Although poisons have been used in warfare for centuries, it was rapid advances in science and engineering and the rise of the modern chemical industry that made the mass production of toxic chemicals possible. The horrors of gas warfare led to the signing of the Geneva Protocol in 1925, which banned the use of \"asphyxiating, poisonous or other gases\" in war, but did not ban the production and stockpiling of chemical agents. Large arsenals containing nerve agents such as Sarin and VX were acquired during the years of the Cold War, these agents surpass the lethality of traditional World War I agents more than a thousand-fold. Tragically, chemical weapons were also used over much of the past century, most extensively during the Iran-Iraq War.

Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be used to confirm exposure in humans. A highly accurate method to detect G- and V-series OPNA adducts to BChE in 75 μL of filtered blood, serum, or plasma has been developed using immunomagnetic separation (IMS) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS). The reported IMS method captures > 88 % of the BChE in a specimen and corrects for matrix effects on peptide calibrators. The optimized method has been used to quantify baseline BChE levels (unadducted and OPNA-adducted) in a matched-set of serum, plasma, and whole blood (later processed in-house for plasma content) from 192 unexposed individuals to determine the interchangeability of the tested matrices. The results of these measurements demonstrate the ability to accurately measure BChE regardless of the format of the blood specimen received. Criteria for accepting or denying specimens were established through a series of sample stability and processing experiments. The results of these efforts are an optimized and rugged method that is transferrable to other laboratories and an increased understanding of the BChE biomarker in matrix.

A new rapid, sensitive and reliable method was developed for the determination of phosgene in air samples using thermal desorption (TD) followed by gas chromatography–mass spectrometry (GC-MS). The method is based on a fast (10 min) active sampling of only 1 L of air onto a Tenax® GR tube doped with 0.5 mL of derivatizing mixture containing dimercaptotoluene and triethylamine in hexane solution. Validation of the TD-GC-MS method showed a low limit of detection (40 ppbv), acceptable repeatability, intermediate fidelity (relative standard deviation within 12 %) and excellent accuracy (>95 %). Linearity was demonstrated for two concentration ranges (0.04 to 2.5 ppmv and 2.5 to 10 ppmv) owing to variation of derivatization recovery between low and high concentration levels. Due to its simple on-site implementation and its close similarity with recommended operating procedure (ROP) for chemical warfare agents vapour sampling, the method is particularly useful in the process of verification of the Chemical Weapons Convention. Figure Doping of tube with derivatizing mixture before sampling

The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC “Annex on Chemicals” some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman’s assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.

The inspection regime under the Chemical Weapons Convention (CWC) requires both the ability to identify low levels of chemical agents, precursors, and decomposition products in complex mixtures while at the same time not exposing the inspection site to the risk of loss of confidential information related to the chemical composition of the sample. The method of choice for such detection of low levels of chemical agents is gas chromatography separation with mass spectral identification (GC/MS), but the usual method of such analysis-an extensive examination of the GC/MS data file for spectra matching the compounds of interest-is both time-consuming, prone to missing low-level components, and difficult to ensure that chemicals not relevant to the CWC are not discovered. To deal with these problems, AMDIS (Automatic Mass spectral Deconvolution and Identification System), a method of automatically finding all of the distinct chemical components in the GC/MS data file and then compare them to a library of spectra of chemicals relevant to the CWC was developed.

An overview of approach, standard procedure and results following the participation in the 6th Organisation for the Prohibition of Chemical Weapons (OPCW) Chemical Weapons Convention (CWC) Chemical Analysis Competency Testing (CCACT) are presented. CCACT is an initiative from OPCW to assist state party laboratories to build the latter's capacity in preparing for the Proficiency Test (PT). With an aim to join the PT, the Science and Research Institute for Defence's (STRIDE) Chemical Analysis Laboratory participated in the CCACT in 2018 to detect and identify chemical weapons for environmental analysis certification. Identification of chemical weapons is challenging not only because these chemicals are unstable and very toxic, but the analysis and the interpretation of results are required to be at a certain level of competency for all participating laboratories. As a general guideline a sample has to be analysed by at least two different analytical techniques, and at least one of these techniques use spectrometry. All these spiking chemicals from the given water sample was found which are Quinuclidin-3-ol and 2, 2-Diphenyl-2-hydroxyacetic acid classified as Schedule 2 precursor or reactant of chemical weapons, and Methyldiethanolamine (MDEA)classified as Schedule 3 precursor or reactant of chemical weapons.

Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman), and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid-phase extraction coupled with high-performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3 to 0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101–105 %) and high precision (5–8 %) for the detection of these five nerve agent hydrolysis products in serum.

Issue Title: Analysis of Chemicals Relevant to the Chemical Weapons Convention

Ricin is a toxic protein derived from castor beans and composed of a cytotoxic A chain and a galactose-binding B chain linked by a disulfide bond, which can inhibit protein synthesis and cause cell death. Owing to its high toxicity, ease of preparation, and lack of medical countermeasures, ricin has been listed as both chemical and biological warfare agents. For homeland security or public safety, the unambiguous, sensitive, and rapid methods for identification and quantification of ricin in complicated matrices are of urgent need. Mass spectrometric analysis, which provides specific and sensitive characterization of protein, can be applied to confirm and quantify ricin. Here, we report a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method in which ricin was extracted and enriched from serum by immunocapture using anti-ricin monoclonal antibody 3D74 linked to magnetic beads, then digested by trypsin, and analyzed by LC-ESI-MS/MS. Among 19 distinct peptides observed in LC-quadrupole/time of flight-MS (LC-QTOF-MS), two specific and sensitive peptides, T 7A ( 49 VGLPINQR 56 ) and T 14B ( 188 DNCLTSDSNIR 198 ), were chosen, and a highly sensitive determination of ricin was established in LC-triple quadrupole-MS (LC-QqQ-MS) operating in multiple reaction monitoring mode. These specific peptides can definitely distinguish ricin from the homologous protein Ricinus communis agglutinin (RCA120), even though the amino acid sequence homology of the A-chain of ricin and RCA120 is up to ca. 93 % and that of B-chain is ca. 85 %. Furthermore, peptide T 7A was preferred in the quantification of ricin because its sensitivity was at least one order of magnitude higher than that of the peptide T 14B . Combined with immunocapture enrichment, this method provided a limit of detection of ca. 2.5 ng/mL and the limit of quantification was ca. 5 ng/mL of ricin in serum, respectively. Both precision and accuracy of this method were determined and the RSD was less than 15 %. This established method was then applied to measure ricin in serum samples collected from rats exposed to ricin at the dosage of 50 μg/kg in an intravenous injection manner. The results showed that ca. 10 ng/mL of the residual ricin in poisoned rats serum could be detected even at 12 h after exposure.