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

Abstract

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.

Structural characterization of Chemical Weapons Convention‐related phosphonoselenoates by electron ionization and electrospray ionization mass spectrometry

“…To ensure that the CWC treaty is respected, the detection of trace levels and the identification of CWC‐related compounds are required in a variety of environmental samples. LC/ESI‐MS is also widely used for the analysis of CWC‐related compounds 34 . With the obtained encouraging results from EI‐MS analysis of derivatives 4 , in this section our attention is focused on the ESI spectra of 4 .…”

Synthesis, experimental and molecular dynamics simulation of the ESI-CID spectrum of the nerve agent Novichok analog O-2-methoxyethyl N- [bis(dimethylamino)methylidene]-P-methylphosphonamidate

“…The precise identification of chemicals of concern in a variety of environmental samples [13] is required to comply with the verification regime; the techniques of gas or liquid chromatography (GC or LC) coupled with mass spectrometry (MS) or tandem mass spectrometry (MS/MS) are the primary tools for this task [14]. GC-MS analysis is typically performed under electron ionization (EI) conditions, which is the oldest and still the most used ionization technique for the analysis of CWC-related chemicals [15].…”

“…The LC-MS and LC-MS/MS techniques have opened up the possibility of performing direct analysis of aqueous samples and a greater suitability over GC-MS for the analysis of nonvolatile, highly polar, and very water-soluble compounds, such as degradation products of nerve agents [14,24]. In addition to the advantages above, the need for at least two different spectrometric techniques [16,25] for producing a reliable result makes them crucial for laboratories involved in analyzing CWAs samples to address and successfully complete their analytical task [14].…”

“…Unfortunately, as LC-MS and LC-MS/MS are very instrumentation dependent [14] and establishing in-house spectral libraries for CWC-related chemicals implies dealing with molecules of limited access and high toxicity [26,27]. For these reasons, a safe and rational alternative to determine their mass spectra is to employ computational quantum chemical simulation methods [28], such as the Quantum Chemical Mass Spectrometry method (QCxMS) developed by Grimme's group [29].…”