Specificity enhancement by electrospray ionization multistage mass spectrometry – a valuable tool for differentiation and identification of ‘V’‐type chemical warfare agents

Abstract

The use of chemical warfare agents has become an issue of emerging concern. One of the challenges in analytical monitoring of the extremely toxic 'V'-type chemical weapons [O-alkyl S-(2-dialkylamino)ethyl alkylphosphonothiolates] is to distinguish and identify compounds of similar structure. MS analysis of these compounds reveals mostly fragment/product ions representing the amine-containing residue. Hence, isomers or derivatives with the same amine residue exhibit similar mass spectral patterns in both classical EI/MS and electrospray ionization-MS, leading to unavoidable ambiguity in the identification of the phosphonate moiety. A set of five 'V'-type agents, including O-ethyl S-(2-diisopropylamino)ethyl methylphosphonothiolate (VX), O-isobutyl S-(2-diethylamino)ethyl methylphosphonothiolate (RVX) and O-ethyl S-(2-diethylamino)ethyl methylphosphonothiolate (VM) were studied by liquid chromatography/electrospray ionization/MS, utilizing a QTRAP mass detector. MS/MS enhanced product ion scans and multistage MS(3) experiments were carried out. Based on the results, possible fragmentation pathways were proposed, and a method for the differentiation and identification of structural isomers and derivatives of 'V'-type chemical warfare agents was obtained. MS/MS enhanced product ion scans at various collision energies provided information-rich spectra, although many of the product ions obtained were at low abundance. Employing MS(3) experiments enhanced the selectivity for those low abundance product ions and provided spectra indicative of the different phosphonate groups. Study of the fragmentation pathways, revealing some less expected structures, was carried out and allowed the formulation of mechanistic rules and the determination of sets of ions typical of specific groups, for example, methylphosphonothiolates versus ethylphosphonothiolates. The new group-specific ions elucidated in this work are also useful for screening unknown 'V'-type agents and related compounds, utilizing precursor ion scan experiments.

Oxidation‐assisted structural elucidation of compounds containing a tertiary amine side chain using liquid chromatography mass spectrometry

“…However, difficulties arise in cases where the ESI‐MS/MS spectrum is uninformative or exhibits poor quality, leading to insufficient evidence to match the ESI‐MS/MS spectra to the proposed structure. Several compounds containing an amine side chain, particularly tertiary amines, present information‐poor mass spectra with product ions mostly/only representing the amine‐containing residue . This lack of information is attributed to the strong tendency of the amine side chain to stabilize the positive charge and leads to unavoidable ambiguity in the identification process.…”

Detection of chemical warfare agent simulants and hydrolysis products in biological samples by paper spray mass spectrometry

“…As expected, the SIL analogs resulted in better calculated LODs for TMP and DIMP. In the case of DMMP, d 9 TMP yielded the more reproducible results than when using 13 Cd 3 DIMP as the ISTD. These differences are likely because both DMMP and d 9 TMP are protonated ions, whereas 13 Fig.…”

“…8 Analysis of CWAs by mass spectrometry (MS) has grown substantially in the last 10 years. [9][10][11][12][13] Many of the fielded MS methods require the use of gas chromatography (GC) and/or liquid chromatography (LC), which pose difficulties for rapid analysis due to sample preparation needs 14 and lengthy run times. Several rapid, on-site methods have been proposed, such as atmospheric pressure chemical ionization (APCI) MS, 15,16 selected ion flow tube (SIFT) MS, 17,18 and proton transfer reaction (PTR) MS. 19 However, these methods can only measure a limited range of volatile small molecules and have strong carry-over between runs, which decreases the rate of sample analysis.…”

Structural elucidation of V‐type nerve agents by liquid chromatography/electrospray ionization mass spectrometry

“…Several approaches have been implemented for the structural elucidation of V‐nerve agent derivatives and their isomers. Weissberg et al 8 and Housman et al 9 demonstrated the use of ESI‐MS 2 and ESI‐MS 3 experiments in cases where the information derived from routine ESI‐MS 2 experiments was insufficient for structural elucidation. More recently, Snyder et al 2 demonstrated the applicability of a single‐linear quadrupole ion trap to acquire two‐dimensional mass spectrometry data (2D MS/MS) for the identification of V‐nerve agents.…”