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

Abstract

Paper spray ionization coupled to a high resolution tandem mass spectrometer (a quadrupole orbitrap) was used to identify and quantitate chemical warfare agent (CWA) simulants and their hydrolysis products in blood and urine. Three CWA simulants, dimethyl methylphosphonate (DMMP), trimethyl phosphate (TMP), and diisopropyl methylphosphonate (DIMP), and their isotopically labeled standards were analyzed in human whole blood and urine. Calibration curves were generated and tested with continuing calibration verification standards. Limits of detection for these three compounds were in the low ng mLrange for the direct analysis of both blood and urine samples. Five CWA hydrolysis products, ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), cyclohexyl methylphosphonic acid (CHMPA), and pinacolyl methylphosphonic acid (PinMPA), were also analyzed. Calibration curves were generated in both positive and negative ion modes. Limits of detection in the negative ion mode ranged from 0.36 ng mL −1 to 1.25 ng mL −1 in both blood and urine for the hydrolysis products. These levels were well below those found in victims of the Tokyo subway attack of 2 to 135 ng mL. 1 Improved stability and robustness of the paper spray technique in the negative ion mode was achieved by the addition of chlorinated solvents. These applications demonstrate that paper spray mass spectrometry (PS-MS) can be used for rapid, sample preparation-free detection of chemical warfare agents and their hydrolysis products at physiologically relevant concentrations in biological samples.

On‐substrate derivatization for detection of highly volatile G‐series chemical warfare agents via paper spray mass spectrometry

“…Rhodamine B was dissolved in methanol arbitrarily to provide color differentiation in spot size experiments. 2‐DMAMP was prepared to a concentration of 420.0 μg/mL for 2.0 μL aliquot application to the paper spray cartridge, and allowed to dry for 24 h. A spotting scaffold, details of which were published previously, was utilized to ensure the location and dosing repeatability of the DMAMP chemistry …”

“…This technique has a wide range of applications with many compatible analytes including biological tissues and fluids, foodstuffs, inks, bacteria, and illicit drugs . More relevantly, explosives, herbicides from aqueous matrices, pesticides, and CWA simulants from biofluids have been shown to be effectively analyzed via paper spray mass spectrometry (PS‐MS). The spray substrate has been subjected to a multitude of modifications including the addition of metal–organic‐frameworks (MOFs), carbon nanotubes, silica, urea, silanes, molecularly imprinted polymer (MIPs), and wax printing, with each resulting in a specialized system catering to a specific matrix or target chemistry.…”

A statistical approach to optimizing paper spray mass spectrometry parameters

“…Desorption electrospray ionization (DESI) and direct analysis in real time (DART) paved the way for a variety of ambient ionization techniques for mass spectrometry, which are utilized for the direct analysis of samples without extensive sample preparation or separations . Paper spray mass spectrometry (PS‐MS) is one such example as it provides a rapid and cost‐effective method for the analysis of small organic molecules, complex mixtures, peptides, and intact proteins in a variety of environmental and biological matrices with little to no sample preparation . Samples can be preloaded onto triangular‐shaped paper spray substrates, or the substrates themselves can be used to wipe the sample off of various surfaces .…”

“…[2][3][4] Paper spray mass spectrometry (PS-MS) is one such example as it provides a rapid and cost-effective method for the analysis of small organic molecules, complex mixtures, peptides, and intact proteins in a variety of environmental and biological matrices with little to no sample preparation. [5][6][7][8] Samples can be preloaded onto triangular-shaped paper spray substrates, or the substrates themselves can be used to wipe the sample off of various surfaces. 5,9 Pre-loading analyte onto the paper substrates allows for potential long-term storage of the sample prior to analysis, which is beneficial when sample collection occurs in the field.…”

A Low-Cost, Simplified Platform of Interchangeable, Ambient Ionization Sources for Rapid, Forensic Evidence Screening on Portable Mass Spectrometric Instrumentation

“…As there is no need for pneumatics or extensive sample preparation, it is one of the simplest techniques for coupling to portable MS systems. PSI has been applied broadly in the forensic community, such as quantitative determination of abused drugs in whole blood [40] and rapid detection of explosives [49] and chemical warfare agent simulants [50]. It has been shown highly proficient towards drug evidence screening on portable MS systems, as well [9,19,22,51].…”