Development of Ion Mobility Spectrometry with Novel Atmospheric Electron Emission Ionization for Field Detection of Gaseous and Blister Chemical Warfare Agents.

Drift tube ion mobility spectrometry with a novel atmospheric electron emission (AEE) source was developed for determination of gaseous and blister chemical warfare agents (CWAs) in negative mode. The AEE source was fabricated from an aluminum substrate electrode covered with 1 µm silver nanoparticle-dispersed silicone resin and a thin gold layer. This structure enabled stable tunneling electron emission upon the application of more than 11 V potential under atmospheric pressure. The reactant ion peak (RIP) was observed for the reduced mobility constant ( K0) of 2.18 and optimized at the charging voltage of 20 V. This RIP was assigned to O2- by using a mass spectrometer. Hydrogen cyanide was detected as a peak ( K0 = 2.47) that was discriminatively separated from the RIP (resolution = 1.4), with a limit of detection (LOD) of 0.057 mg/m3, and assigned to CN- and OCN-. Phosgene was detected as a peak ( K0 = 2.36; resolution = 1.2; and LOD = 0.6 mg/m3), which was assigned to Cl-. Lewisite 1 was detected as two peaks ( K0 = 1.68 and 1.34; LOD = 12 and 15 mg/m3). The K0 = 1.68 peak was ascribed to a mixture of adducts of molecules or the product of hydrolysis with oxygen or chloride. Cyanogen chloride, chlorine, and sulfur mustard were also well detected. The detection performance with the AEE source was compared with those under corona discharge and 63Ni ionizations. The advantage of the AEE source is the simple RIP pattern (only O2-), and the characteristic marker ions contribute to the discriminative CWAs detection.

Development of a gas-cylinder-free plasma desorption/ionization system for on-site detection of chemical warfare agents.

A gas-cylinder-free plasma desorption/ionization system was developed to realize a mobile on-site analytical device for detection of chemical warfare agents (CWAs). In this system, the plasma source was directly connected to the inlet of a mass spectrometer. The plasma can be generated with ambient air, which is drawn into the discharge region by negative pressure in the mass spectrometer. High-power density pulsed plasma of 100 kW could be generated by using a microhollow cathode and a laboratory-built high-intensity pulsed power supply (pulse width: 10-20 µs; repetition frequency: 50 Hz). CWAs were desorbed and protonated in the enclosed space adjacent to the plasma source. Protonated sample molecules were introduced to the mass spectrometer by airflow through the discharge region. To evaluate the analytical performance of this device, helium and air plasma were directly irradiated to CWAs in the gas-cylinder-free plasma desorption/ionization system and the protonated molecules were analyzed by using an ion-trap mass spectrometer. A blister agent (nitrogen mustard 3) and nerve gases [cyclohexylsarin (GF), tabun (GA), and O-ethyl S-2-N,N-diisopropylaminoethyl methylphosphonothiolate (VX)] in solution in n-hexane were applied to the Teflon rod and used as test samples, after solvent evaporation. As a result, protonated molecules of CWAs were successfully observed as the characteristic ion peaks at m/z 204, 181, 163, and 268, respectively. In air plasma, the limits of detection were estimated to be 22, 20, 4.8, and 1.0 pmol, respectively, which were lower than those obtained with helium plasma. To achieve quantitative analysis, calibration curves were made by using CWA stimulant dipinacolyl methylphosphonate as an internal standard; straight correlation lines (R(2) = 0.9998) of the peak intensity ratios (target per internal standard) were obtained. Remarkably, GA and GF gave protonated dimer ions, and the ratios of the protonated dimer ions to the protonated monomers increased with the amount of GA and GF applied.

Real-time air monitoring of mustard gas and Lewisite 1 by detecting their in-line reaction products by atmospheric pressure chemical ionization ion trap tandem mass spectrometry with counterflow ion introduction.

A new method enabling sensitive real-time air monitoring of highly reactive chemical warfare agents, namely, mustard gas (HD) and Lewisite 1 (L1), by detecting ions of their in-line reaction products instead of intact agents, is proposed. The method is based on corona discharge-initiated atmospheric pressure chemical ionization coupled with ion trap tandem mass spectrometry (MS(n)) via counterflow ion introduction. Therefore, it allows for highly sensitive and specific real-time detection of a broad range of airborne compounds. In-line chemical reactions, ionization reactions, and ion fragmentations of these agents were investigated. Mustard gas is oxygenated in small quantity by reactive oxygen species generated in the corona discharge. With increasing air humidity, the MS(2) signal intensity of protonated molecules of mono-oxygenated HD decreases but exceeds that of dominantly existing intact HD. This result can be explained in view of proton affinity. Lewisite 1 is hydrolyzed and oxidized. As the humidity increases from zero, the signal of the final product, namely, didechlorinated, dihydroxylated, and mono-oxygenated L1, quickly increases and reaches a plateau, giving the highest MS(2) and MS(3) signals among those of L1 and its reaction products. The addition of minimal moisture gives the highest signal intensity, even under low humidity. The method was demonstrated to provide sufficient analytical performance to meet the requirements concerning hygienic management and counter-terrorism. It will be the first practical method, in view of sensitivity and specificity, for real-time air monitoring of HD and L1 without sample pretreatment.

Sensitive and comprehensive detection of chemical warfare agents in air by atmospheric pressure chemical ionization ion trap tandem mass spectrometry with counterflow introduction.

A highly sensitive and specific real-time field-deployable detection technology, based on counterflow air introduction atmospheric pressure chemical ionization, has been developed for a wide range of chemical warfare agents (CWAs) comprising gaseous (two blood agents, three choking agents), volatile (six nerve gases and one precursor agent, five blister agents), and nonvolatile (three lachrymators, three vomiting agents) agents in air. The approach can afford effective chemical ionization, in both positive and negative ion modes, for ion trap multiple-stage mass spectrometry (MS(n)). The volatile and nonvolatile CWAs tested provided characteristic ions, which were fragmented into MS(3) product ions in positive and negative ion modes. Portions of the fragment ions were assigned by laboratory hybrid mass spectrometry (MS) composed of linear ion trap and high-resolution mass spectrometers. Gaseous agents were detected by MS or MS(2) in negative ion mode. The limits of detection for a 1 s measurement were typically at or below the microgram per cubic meter level except for chloropicrin (submilligram per cubic meter). Matrix effects by gasoline vapor resulted in minimal false-positive signals for all the CWAs and some signal suppression in the case of mustard gas. The moisture level did influence the measurement of the CWAs.

Gas chromatography-mass spectrometry with spiral large-volume injection for determination of fluoridated phosphonates produced by fluoride-mediated regeneration of nerve agent adduct in human serum.

A sensitive method for determination of fluoridated phosphonates produced by fluoride-mediated regeneration of nerve agent adduct in human serum was developed using gas chromatography-mass spectrometry (GCMS) with large-volume injection. The GC injection was administered using stomach-type spiral injector (LVI, AiSTI SCIENCE) enabling introduction of only target compounds from 50 µL ethyl acetate extract after purging the solvent. For GCMS analysis of sarin (GB), 670 times higher sensitivity, based on limit of detection (LOD, S/N = 3, on extracted ion chromatogram (EIC) at m/z 99), was achieved using this injection (50 µL) compared to that achieved using 1 µL split injection (ratio 20:1). Ethyl (EtGB), isopropyl (GB), n-propyl (nPrGB), isobutyl (iBuGB), pinacolyl (GD), cyclohexyl (GF) methylphosphonofluoridates, and O-ethyl N, N-dimethylphosphoramidofluoridate (GAF) were detected with low LOD (15-75 pg/mL) and sharp peak shapes (high practical plate number (defined as 5.54 x (tR/Wh)2, where tR is the retention time and Wh is the bandwidth at half-height): 1100000-2400000) in GCMS using a polar separation column, electron ionization, and quadruple mass analyzer. During the analysis of fluoridated phosphonate-spiked ethyl acetate extract of solid phase extraction (SPE, Bond Elut NEXUS) from fluoride-mediated regeneration of blank human plasma, LOD (on EIC at m/z 99 except for GAF (m/z 126)) were 25-140 pg/mL with sharp peak shapes. The reaction recoveries in fluoride-mediated regeneration of plasma, which was inhibited by GB, GD, GA, GF, VX, and Russian VX (10 ng/mL), were 49-114% except for GD (10%). The concentration levels of 0.3-1 ng/mL of nerve agents in plasma could be determined.

In-Line Reactions and Ionizations of Vaporized Diphenylchloroarsine and Diphenylcyanoarsine in Atmospheric Pressure Chemical Ionization Mass Spectrometry.

We propose detecting a fragment ion (Ph2As(+)) using counter-flow introduction atmospheric pressure chemical ionization ion trap mass spectrometry for sensitive air monitoring of chemical warfare vomiting agents diphenylchloroarsine (DA) and diphenylcyanoarsine (DC). The liquid sample containing of DA, DC, and bis(diphenylarsine)oxide (BDPAO) was heated in a dry air line, and the generated vapor was mixed into the humidified air flowing through the sampling line of a mass spectrometer. Humidity effect on the air monitoring was investigated by varying the humidity of the analyzed air sample. Evidence of the in-line conversion of DA and DC to diphenylarsine hydroxide (DPAH) and then BDPAO was obtained by comparing the chronograms of various ions from the beginning of heating. Multiple-stage mass spectrometry revealed that the protonated molecule (MH(+)) of DA, DC, DPAH, and BDPAO could produce Ph2As(+) through their in-source fragmentation. Among the signals of the ions that were investigated, the Ph2As(+) signal was the most intense and increased to reach a plateau with the increased air humidity, whereas the MH(+) signal of DA decreased. It was suggested that DA and DC were converted in-line into BDPAO, which was a major source of Ph2As(+). Graphical Abstract ᅟ.

Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22µg sarin (GB), 100µg soman (GD), 210µg tabun (GA), 55µg cyclohexylsarin (GF), 4.8µg sulfur mustard, 390µg nitrogen mustard 1, 140µg of nitrogen mustard 2, 130µg nitrogen mustard 3, 120µg of 2-chloroacetophenone and 990µg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation.