Characterization and Study on Fragmentation Pathways of a Novel Nerve Agent, ‘Novichok (A234)’, in Aqueous Solution by Liquid Chromatography–Tandem Mass Spectrometry

Abstract

As a first step toward studying the properties of Novichok (ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)), we investigated its degradation products and fragmentation pathways in aqueous solution at different pH levels by liquid chromatography–tandem mass spectrometry. A234 was synthesized in our laboratory and characterized by nuclear magnetic resonance spectroscopy. Three sets of aqueous samples were prepared at different pH levels. A stock solution of A234 was prepared in acetonitrile at a concentration of 1 mg/mL and stored at −20 °C until use. Aqueous samples (0.1 mg/mL) were prepared by diluting the stock solution with deionized water. The acidic aqueous sample (pH = 3.5) and basic aqueous sample (pH = 9.4) were prepared using 0.01 M acetic acid and 0.01 M potassium carbonate, respectively. The analysis of the fragmentation patterns and degradation pathways of A234 showed that the same degradation products were formed at all pH levels. However, the hydrolysis rate of A234 was fastest under acidic conditions. In all three conditions, the fragmentation pattern and the major degradation product of A234 were determined. This information will be applicable to studies regarding the decontamination of Novichok and the trace analysis of its degradation products in various environmental matrices.

Recent research on Novichok

“…In the meantime, theoretical and mass spectrometry studies have appeared that ascertain the structures shown in Fig. 1 (Bhakkoa et al 2019 ; Lee et al 2021 ; Jeong et al 2021 ).…”

“…(iv) Analytical chemistry and biomonitoring: sophisticated analytical methods, such as LC-MS/MS, must be used to analytically characterize Novichok agents (e.g., A 234). Recent progress in this direction has been reported (Lee et al 2021). Another A 234 (Cai et al 2018;Lee et al 2021).…”

“…Recent progress in this direction has been reported (Lee et al 2021). Another A 234 (Cai et al 2018;Lee et al 2021). A 234 has been identified as the agent of the Skripal case (Bhakhoa et al 2019) promising avenue of research is blood protein adductomics (Sabbioni and Day 2022).…”

“…1 ) was alleged by the British government to have been used to poison the Skripals, and its identity was confirmed by the Organization for the Prohibition of Chemical Weapons (OPCW). After the British authorities classified this incident as poisoning terrorism based on the use of a novel series of nerve agents, OPCW ratified all Novichok-based components in the Chemical Weapons Convention lists in June 2020 (Lee et al 2021 ).

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Fig. 1 Structural formulae of the related Novichok agents A 232 and A 234 (Cai et al 2018 ; Lee et al 2021 ). A 234 has been identified as the agent of the Skripal case (Bhakhoa et al 2019 )

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