A novel active capillary dielectric barrier discharge plasma ionization (DBDI) technique for mass spectrometry is applied to the direct detection of 13 chemical warfare related compounds, including sarin, and compared to secondary electrospray ionization (SESI) in terms of selectivity and sensitivity. The investigated compounds include an intact chemical warfare agent and structurally related molecules, hydrolysis products and/or precursors of highly toxic nerve agents (G-series, V-series, and "new" nerve agents), and blistering and incapacitating warfare agents. Well-defined analyte gas phase concentrations were generated by a pressure-assisted nanospray with consecutive thermal evaporation and dilution. Identification was achieved by selected reaction monitoring (SRM). The most abundant fragment ion intensity of each compound was used for quantification. For DBDI and SESI, absolute gas phase detection limits in the low ppt range (in MS/MS mode) were achieved for all compounds investigated. Although the sensitivity of both methods was comparable, the active capillary DBDI sensitivity was found to be dependent on the applied AC voltage, thus enabling direct tuning of the sensitivity and the in-source fragmentation, which may become a key feature in terms of field applicability. Our findings underline the applicability of DBDI and SESI for the direct, sensitive detection and quantification of several CWA types and their degradation products. Furthermore, they suggest the use of DBDI in combination with hand-held instruments for CWAs on-site monitoring.

Abstract. Active capillary plasma ionization is a highly efficient ambient ionization method. Its general principle of ion formation is closely related to atmospheric pressure chemical ionization (APCI). The method is based on dielectric barrier discharge ionization (DBDI), and can be constructed in the form of a direct flowthrough interface to a mass spectrometer. Protonated species ([M + H] + ) are predominantly formed, although in some cases radical cations are also observed. We investigated the underlying ionization mechanisms and reaction pathways for the formation of protonated analyte ([M + H] + ). We found that ionization occurs in the presence and in the absence of water vapor. Therefore, the mechanism cannot exclusively rely on hydronium clusters, as generally accepted for APCI. Based on isotope labeling experiments, protons were shown to originate from various solvents (other than water) and, to a minor extent, from gaseous impurities and/or self-protonation. By using CO 2 instead of air or N 2 as plasma gas, additional species like [M + OH] + and [M − H] + were observed. These gas-phase reaction products of CO 2 with the analyte (tertiary amines) indicate the presence of a radical-mediated ionization pathway, which proceeds by direct reaction of the ionized plasma gas with the analyte. The proposed reaction pathway is supported with density functional theory (DFT) calculations. These findings add a new ionization pathway leading to the protonated species to those currently known for APCI.

This paper characterizes competitive binding, electrokinetic capillary-based immunoassays for urinary methadone using reagents which were commercialized for a fluorescence polarization immunoassay. After incubation of 25 microL urine with the reactants, a small aliquot of the mixture is applied onto a fused-silica capillary and the unbound fluorescein-labeled methadone tracer is monitored by capillary electrophoresis with on-column laser-induced fluorescence detection. Configurations in presence and absence of micelles were investigated, found to be capable of recognizing urinary methadone concentrations > or = 10 ng/mL, and shown to be suitable for rapid methadone screening of patient urines. Based upon shorter run times and a much better separation of free tracer and antibody-tracer complex, conditions without micelles are preferred. For confirmation analysis of urinary methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), capillary electrophoresis in a pH 4.6 ammonium acetate-acetic acid buffer was interphased to an atmospheric pressure ionization triple quadrupole mass spectrometry system. Using positive ion electrospray ionization and the tandem mass spectrometry mode with collision-induced dissociation in the collision cell, fragmentation of the two substances was determined. For confirmation via direct urine injection or application of a urinary extract, in-source fragmentation was employed and the first quadrupole was operated in the selected ion monitoring mode by switching between the masses of relevant precursor/product ion sets for methadone (m/z = 310, 265) and EDDP (m/z = 278, 249, 234). This capillary electrophoresis-mass spectrometry approach is shown to permit the confirmation of methadone and EDDP in patient urines that tested positive for methadone using electrokinetic capillary-based immunoassays, a fluorescence polarization immunoassay, and capillary electrophoresis with UV absorption detection.

Abstract. An active capillary plasma ionization (ACI) source was coupled to a handheld mass spectrometer (Mini 10.5; Aston Labs, West Lafayette, IN, USA) and applied to the direct gas-phase detection and quantification of chemical warfare agent (CWA) related chemicals. Complementing the discontinuous atmospheric pressure interface (DAPI) of the Mini 10.5 mass spectrometer with an additional membrane pump, a quasi-continuous sample introduction through the ACI source was achieved. Nerve agent simulants (three dialkyl alkylphosphonates, a dialkyl phosporamidate, and the pesticide dichlorvos) were detected at low gas-phase concentrations with limits of detection ranging from 1.0 μg/m 3 to 6.3 μg/m 3 . Our results demonstrate a sensitivity enhancement for portable MS-instrumentation by using an ACI source, enabling direct, quantitative measurements of volatile organic compounds. Due to its high sensitivity, selectivity, low power consumption (<80 W) and weight (<13 kg), this instrumentation has the potential for direct on-site CWA detection as required by military or civil protection.

Ultrasensitive direct gas-phase detection of chemical warfare agents (CWAs) is demonstrated utilizing active capillary plasma ionization and triple quadrupole mass spectrometry (MS) instrumentation. Four G- agents, two V-agents and various blistering agents [including sulfur mustard (HD)] were detected directly in the gas phase with limits of detection in the low parts per trillion (ng m(-3)) range. The direct detection of HD was shown for dry carrier gas conditions, but signals vanished when humidity was present, indicating a possible direct detection of HD after sufficient gas phase pretreatment. The method provided sufficient sensitivity to monitor directly the investigated volatile CWAs way below their corresponding minimal effect dose, and in most cases even below the eight hours worker exposure concentration. In general, the ionization is very soft, with little to no in-source fragmentation. Especially for the G-agents, some dimer formation occurred at higher concentrations. This adds complexity, but also further selectivity, to the corresponding mass spectra. Our results show that the active capillary plasma ionization is a robust, sensitive, "plug and play" ambient ionization source suited (but not exclusively) to the very sensitive detection of CWAs. It has the potential to be used with portable MS instrumentation.