Sensitive Untargeted Screening of Nerve Agents and Their Degradation Products Using Liquid Chromatography–High Resolution Mass Spectrometry

Abstract

Nerve agents (NAs) are notorious chemical warfare agents that pose a serious threat to national security and public health. The total number of theoretical chemicals of NAs and their degradation products (DPs) exceeds 410 000, according to 1.A.01–1.A.03 in the Schedules of Chemicals of the Chemical Weapons Convention, which poses great challenges for identification and verification. A three-step integrated untargeted screening strategy was developed based on high-resolution mass spectrometry. First, an extensible homemade library for targeted screening of common classical agents was established. Second, a set of in-source collision-induced dissociation mass spectrometry (MS)-alerting ions was extracted and concluded based on fragmentation behavior studies, which included 40 specific alerting ions and 10 types of characteristic structural fragments from total NAs and their DPs. A novel “alerting ion” searching method was developed to rapidly and sensitively screen whether or not nerve agent-related compounds were present and of which type they were. Third, we built a theoretical exact mass database including 202 accurate masses or molecular formulas, which could cover all structural possibilities of the NAs and their DPs. Comprehensively, the elemental composition of pseudomolecular ions, fragment ions, MS/MS spectra, and isotope pattern information were obtained from the full scan MS/data dependent-MS2 experiments and elucidated for identification of the candidates selected in the screening step. This strategy was successfully applied to the identification of unknown chemicals in real samples with good stability and a low limit of detection of 1–10 ng/mL. These procedures are applicable for trace forensic investigations in cases of the alleged use of nerve agents.

Approaches for assessing performance of high-resolution mass spectrometry–based non-targeted analysis methods

“…1). Unknown/unexpected compound identification is one of the most common and best recognized advantages of NTA; for example, NTA has been used to identify natural and synthetic chemical nerve agents [13],…”

“…Yet, in recent years, management agencies and supporting laboratories have been increasingly tasked with identifying new, unknown, or unexpected chemical stressors in complex samples (notable examples include novel per-and polyfluorinated alkyl substances [PFAS] in soil [4] and water [5,6], biomarkers of exposure to burn pits in serum [7], and discharged pharmaceuticals in wastewater [8]). Furthermore, researchers now routinely face the challenge of characterizing large classes of diverse chemicals (e.g., PFAS [9], illicit designer drugs [10,11] and steroids [12], and chemical warfare agents [13]) that may impact humans and/or ecological species. Existing targeted methods are simply not well suited to address these types of environmental and public health challenges.…”

Synthesis of macroscopic monolithic metal–organic gels for ultra-fast destruction of chemical warfare agents

“…Chemical warfare agents (CWAs) such as sulfur mustard (HD) and VX are lethal chemicals that pose an extreme risk to national security and public health, due to occasional or deliberate emissions. 1 Detoxification of CWAs is an increasing research field that has generated great interest from the scientific and industrial communities. Current state-of-the-art materials for the capture of CWAs mainly rely on impregnated active carbons, which suffer from problems such as slow degradation kinetics, low capacity, and/or a lack of tailorability.…”

Identification of Erythromycin and Clarithromycin Metabolites Formed in Chicken Liver Microsomes Using Liquid Chromatography–High-Resolution Mass Spectrometry

“…Many targeted analytical methods with high selectivity have been developed based on LC-MS or LC-MS/MS to detect MACs in fish, chicken, swine, bovine tissues, meat, eggs, and milk [ 6 , 22 , 23 , 24 , 25 , 26 ]. However, targeted methods can detect known compounds but cannot be used to identify unknown compounds [ 27 , 28 ]. To solve this problem, nontargeted screening based on LC-high-resolution (HR)-MS methods needs to be established for comprehensive analysis of known and unknown compounds [ 29 , 30 ].…”