Analysis of degradation products of nerve agents via post-pentafluorobenzylation liquid chromatography-tandem mass spectrometry

Otsuka, Mai; Tsuge, Kouichiro; Seto, Yasuo; Miyaguchi, Hajime; Uchiyama, Masanobu

doi:10.1016/j.chroma.2018.09.042

Cited by 15 publications

(15 citation statements)

References 31 publications

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“…Accordingly, removal of the excess reagent is a major concern for trace analysis. When derivatizing hydrophilic analytes, hydrophobic reagents such as PFB bromide are usually employed for reversed-phase chromatography . However, the excess reagents are difficult to isolate from the hydrophobic derivatives, and derivatizing reagents may react with matrices in urine, interfering with the detection of trace analytes.…”

Section: Resultsmentioning

confidence: 99%

“…Standard solutions of RMPAs and Novichok hydrolysates in acetonitrile were blended and spiked into urine, and recovery tests were performed. Various extraction conditions, including liquid–liquid extraction, several salting-out assisted liquid–liquid extractions (SALLE), , and SPE, were investigated. For the RMPAs, the extraction was reproducible (EMPA: 62%, other RMPAs: >85%) only when we used SALLE.…”

Section: Resultsmentioning

confidence: 99%

“…Peaks corresponding to the derivatized analytes were detected for 11 compounds; MPGA, which had a relatively large steric hindrance, was not detected, suggesting that the reaction of MPGA with DMTMM did not proceed sufficiently under the reaction conditions. Because the reaction at 90 °C (as with the other derivatization reagents , ) decreased the peak area of DMT-RMPAs, we decided not to include MPGA in this simultaneous analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Conventional derivatization analyses of phosphoric acid and phosphonic acid require harsh conditions because of the insufficient reactivity of derivatizing reagents such as pentafluorobenzyl (PFB) bromide and trimethyl orthoacetate. − The byproducts generated by the reaction of the derivatizing reagent with the matrices of the biological samples cause an increase in the background signal even in tandem MS analysis, which deteriorates the limit of detection (LOD) and selectivity of the analyses. , It is also difficult to perform the silylation method on urine samples . Silylation GC–MS can be applied only to samples with relatively small matrix inhibition (e.g., environmental samples), and its application to urine samples is considered impractical in terms of sensitivity.…”

mentioning

confidence: 99%

“…Conventional derivatization agents (e.g., alkyl halides, acid chlorides, and acid anhydrides) are electronically neutral and hydrophobic and are strongly retained in reversed-phase columns, causing column clogging and background deterioration. , The removal of these agents from processed samples is generally laborious or difficult, and even if possible, there is analyte loss due to postprocessing steps such as extraction, acidification, basification, or concentration. Therefore, we explored derivatization agents that would not be retained in a reversed-phase column and did not require removal (Figure B).…”

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confidence: 99%

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Dimethoxytriadinylation LC–MS/MS of Novichok A-Series Degradation Products in Human Urine

2022

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Novichok A-series compounds, novel nerve agents, pose an increasing threat to citizens worldwide; however, no analytical methods have been reported for detecting their hydrolysis products. Herein, a screening method was developed to detect and identify Novichok A-series degradation products (hydrolysates of A230, A232, A234, A262, and one related compound) and alkyl methylphosphonic acids (RMPAs, conventional nerve agent hydrolysates) using liquid chromatography−tandem mass spectrometry (LC−MS/MS). We identified a suitable derivatization reagent, 4-(4,6dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), and optimized the reaction conditions. The derivatized esters of Novichok A-series degradation products were stable and easily detected. We used this derivatization to achieve the first analytical method for Novichok hydrolysis products in urine (0.40−4.0 ng/mL). The detection limits of the RMPAs (0.1−0.4 ng/mL) were comparable to those presented in previous reports involving pentafluorobenzylation or direct LC−MS/MS. The applicability of the newly developed method was evaluated by analyzing urine samples from the OPCW Fifth Biomedical Proficiency Test.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dimethoxytriadinylation LC–MS/MS of Novichok A-Series Degradation Products in Human Urine

2022

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Liquid Chromatography–Mass Spectrometry in Analysis of Chemicals Related to the Chemical Weapons Convention

Oyler

Maistros

Oyler

et al. 2020

Encyclopedia of Analytical Chemistry

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Liquid chromatography (LC) directly interfaced with mass spectrometry (MS) provides a highly specific and sensitive analytical technique for a wide range of target analytes ranging from small, semi‐volatile chemicals to large biopolymers like proteins, DNA, polar lipids, and carbohydrates. This makes it an important technique in the analysis of biomedical and environmental samples for chemical warfare agents (CWAs) and biological toxins. In LC, like gas chromatography/mass spectrometry (GC/MS), target analytes can be separated from other complex matrix components through chromatographic mechanisms prior to being introduced into a mass spectrometer for unequivocal identification and quantification. The advent of electrospray and matrix‐assisted laser desorption ionization made it possible to introduce molecules efficiently from the liquid or solid phase into the gas phase for mass spectrometric analysis. The advantage of LC over gas chromatography (GC) is that polar CWA degradation products and metabolites, protein toxins and biomarker adducts like organophosphate nerve agent (OPNA)‐protein adducts and sulfur mustard‐protein and DNA adducts can be readily resolved and isolated from complex matrices for mass spectrometric identification and quantification. The disadvantage to LC for this analysis is that there are many more variables involved in the efficient and robust chromatography, volatilization, and ionization of target analytes prior to introduction into the MS as compared to GC/MS, and there is, generally, a wider range of mass spectrometer types with differing capabilities directly interfaced with LC systems currently in use in laboratories making the establishment of reliable spectral libraries more difficult for these systems; individual laboratories can establish their own libraries based on specific instrumentation and specific method parameters provided they have authentic analytical standards for the target analytes of interest. That said, liquid chromatography–mass spectrometry (LC/MS) and liquid chromatography–tandem mass spectrometry (LC/MSMS) are a very important technique that every laboratory involved in the analysis of samples for CWAs, their degradation products and metabolites, and toxins should have in their arsenal in order to successfully address and complete this analytical mission. This article briefly describes method theory and recent method applications to the analysis of these compounds in biomedical and environmental samples which remain important to the international community because of their potential use as terrorist and warfare threats.

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Derivatization and Modification of Chemical Warfare Agents and Their Related Compounds for LC‐MS‐Based Analytical Applications

Weissberg

Madmon

Dagan

2020

Encyclopedia of Analytical Chemistry

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The development of novel analytical methods to detect and identify chemical warfare agents (CWAs), their degradation products, metabolites, and precursors is of high importance as terrorist groups and radical regimes use or plan to use chemical weapons against civilians or military targets. Gas chromatography (GC) and liquid chromatography (LC), usually hyphenated with mass spectrometry (MS), are the major techniques used to detect and identify chemicals of concern according to the chemical convention. In this mini‐review, we describe the present state of research on the derivatization and modification of CWAs and related compounds for LC‐MS and atmospheric pressure ionization (API)‐based analysis reported in the open literature during the last 15 years. The more polar, reactive, or highly volatile agents are derivatized to expedite chromatography and to impart properties valuable for sensitive detection and identification by MS. In this article, we focus on trace analysis of CWAs, mostly G‐type nerve agents, blister agents (sulfur mustard (HD)), and the most famous blood agent, cyanide. Analytical applications are mainly in environmental matrices but also in biomedical matrices that support the investigation of CWAs use and monitoring of possible exposure to CWAs.

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Analysis of degradation products of nerve agents via post-pentafluorobenzylation liquid chromatography-tandem mass spectrometry

Cited by 15 publications

References 31 publications

Dimethoxytriadinylation LC–MS/MS of Novichok A-Series Degradation Products in Human Urine

Dimethoxytriadinylation LC–MS/MS of Novichok A-Series Degradation Products in Human Urine

Liquid Chromatography–Mass Spectrometry in Analysis of Chemicals Related to the Chemical Weapons Convention

Derivatization and Modification of Chemical Warfare Agents and Their Related Compounds for LC‐MS‐Based Analytical Applications

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