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

Abstract

AbstractLiquid 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.