Derivatization-Assisted Sensitive Detection of NovichokAgents by Gas Chromatography–Mass Spectrometry for the Verificationof Environmental and Biomedical Samples

Abstract Novichok agents are newly added chemical warfare agents in Schedule 1 of the Chemical Weapons Convention. Due to their poor chromatographic properties and the presence of relatively polar functional groups, the analytical response of Novichok agents in GC–MS is low. In order to overcome this limitation, a derivatization-assisted sensitive detection method for Novichok agents (A230, A232, and A234) at trace levels has been developed. This method harnesses the higher sensitivity achieved through derivatization of Novichok agents with sodium hexafluoroisopropoxide (NaHFIP), followed by GC-PCI-MS/MS analysis. The mass spectral characteristics of the prepared hexafluoroisopropoxy (HFIP) derivatives of Novichok agents were investigated. The MS/MS parameters and the reagent gas were optimized to enhance the sensitivity of detection of these agents using GC-PCI-MS/MS. The proposed derivatization-assisted detection of Novichok agents offers several advantages, including the use of less toxic derivatives, significantly improved sensitivity and chromatographic properties, and low limits of detection (0.05–0.1 ng/mL). This approach is highly suitable for off-site detection of Novichok agents in environmental as well as biomedical samples for forensic investigations, where trace-level analysis is critical. The developed methodology was applied to verify the presence of Novichok agents in various matrices, including tap water, soil, plasma, and urine. A drastic enhancement in the limit of detection for Novichok agents was observed from all the studied matrices using the proposed derivatization-assisted method. The applicability of the method was also tested using a sample from the 10th Biomedical Proficiency Test conducted by the Organisation for the Prohibition of Chemical Weapons (OPCW).