Post-operative isoflurane has been observed to be present in the end-tidal breath of patients who have undergone major surgery, for several weeks after the surgical procedures. A major new non-controlled, non-randomized, and open-label approved study will recruit patients undergoing various surgeries under different inhalation anaesthetics, with two key objectives, namely (1) to record the washout characteristics following surgery, and (2) to investigate the influence of a patient’s health and the duration and type of surgery on elimination. In preparation for this breath study using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), it is important to identify first the analytical product ions that need to be monitored and under what operating conditions. In this first paper of this new research programme, we present extensive PTR-TOF-MS studies of three major anaesthetics used worldwide, desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F), and isoflurane (CF3CHClOCHF2) and a fourth one, which is used less extensively, enflurane (CHF2OCF2CHFCl), but is of interest because it is an isomer of isoflurane. Product ions are identified as a function of reduced electric field (E/N) over the range of approximately 80 Td to 210 Td, and the effects of operating the drift tube under ‘normal’ or ‘humid’ conditions on the intensities of the product ions are presented. To aid in the analyses, density functional theory (DFT) calculations of the proton affinities and the gas-phase basicities of the anaesthetics have been determined. Calculated energies for the ion-molecule reaction pathways leading to key product ions, identified as ideal for monitoring the inhalation anaesthetics in breath with a high sensitivity and selectivity, are also presented.

The high sensitivity of proton transfer reaction-mass spectrometry (PTR-MS) makes it a suitable analytical tool for detecting trace compounds. Its specificity is primarily determined by the accuracy of identifying the m/ z of the product ions specific to a particular compound. However, specificity can be enhanced by changing the product ions (concentrations and types) through modifying the reduced electric field. For current PTR-MS systems, this is not possible for trace compounds that would only be present in the reaction chamber of a PTR-MS for a short time (seconds). For such circumstances, it is necessary to change the reduce electric field swiftly if specificity enhancements are to be achieved. In this paper we demonstrate such a novel approach, which permits any compound that may only be present in the drift tube for seconds to be thoroughly investigated. Specifically, we have developed hardware and software which permits the reaction region's voltages to be rapidly switched at a frequency of 0.1-5 Hz. We show how this technique can be used to provide a higher confidence in the identification of compounds than is possible by keeping to one reduced electric field value through illustrating the detection of explosives. Although demonstrated for homeland security applications, this new technique has applications in other analytical areas and disciplines where rapid changes in a compound's concentration can occur, for example, in the Earth's atmosphere, plant emissions and in breath. Importantly, this adaptation provides a method for improved selectivity without expensive instrumental changes or the need for high mass resolution instruments.

In the present work we present an investigation of the negative ion-molecule chemistry of the anaesthetics isoflurane, ISOF, and enflurane, ENF, in an ion mobility spectrometry/mass spectrometry (IMS/MS), in both air and nitrogen. Hexachloroethane (HCE) was introduced in both air and nitrogen to produce Cl- as a reactant ion. This study was undertaken owing to uncertainties in the chemical processes, which lead to the cluster ions reported in other work (Eiceman et al. Anal. Chem. 61, 1093-1099, 1). In particular for ISOF the product ion observed was ISOF.Cl-, and it was suggested that the Cl- was formed by dissociative electron attachment (DEA) although there was mention of a chlorine containing contaminant. We show in this study that ISOF and ENF do not produce Cl- in an IMS system either by capture of free electrons or reaction with O2-. This demonstrates that the Cl- containing ions, reported in the earlier study, must have been the result of a chlorine containing contaminant as suggested. The failure of ISOF and ENF to undergo DEA was initially surprising given the high calculated electron affinities, but further calculations showed that this was a result of the large positive vertical attachment energies (VAEs). This experimental work has been supported by electronic structure calculations at the B3LYP level, and is consistent with those obtained in a crossed electron-molecular beam two sector field mass spectrometer. An unusual observation is that the monomer complexes of ISOF and ENF with O2- are relatively unstable compared with the dimer complexes. Graphical Abstract ᅟ.

A key issue with any analytical system based on mass spectrometry with no initial separation of compounds is to have a high level of confidence in chemical assignment. This is particularly true for areas of security, such as airports, and recent terrorist attacks have highlighted the need for reliable analytical instrumentation. Proton transfer reaction mass spectrometry is a useful technology for these purposes because the chances of false positives are small owing to the use of a mass spectrometric analysis. However, the detection of an ion at a given m/z for an explosive does not guarantee that that explosive is present. There is still some ambiguity associated with any chemical assignment owing to the presence of isobaric compounds and, depending on mass resolution, ions with the same nominal m/z. In this article we describe how for the first time the use of a radio frequency ion-funnel (RFIF) in the reaction region (drift tube) of a proton transfer reaction-time-of-flight-mass spectrometer (PTR-ToF-MS) can be used to enhance specificity by manipulating the ion-molecule chemistry through collisional induced processes. Results for trinitrotoluene, dinitrotoluenes, and nitrotoluenes are presented to demonstrate the advantages of this new RFIF-PTR-ToF-MS for analytical chemical purposes.

Here we demonstrate the use of a switchable reagent ion proton transfer reaction mass spectrometry (SRI-PTR-MS) instrument to improve the instrument's selectivity for the detection of the explosive compounds 2,4,6 trinitrotoluene (TNT), 1,3,5 trinitrobenzene (TNB), pentaerythritol tetranitrate (PETN), and cyclotrimethylenetrinitramine (RDX). Selectivity is improved owing to the production of different product ions resulting from changes in the reagent ion-molecule chemistry. To be of use as an analytical tool for homeland security applications, it is important that the reagent ions (and hence product ions) can be rapidly changed (within seconds) from H3O to another dominant ion species if the technology is to be acceptable. This paper presents measurements that show how it is possible to rapidly switch the reagent ion from H3O+ to either O-2(+) or NO+ to enhance selectivity for the detection of the four explosives named above. That switching reagent ions can be done quickly results from the fact that the recombination energies of O-2(+) and NO+ are less than the ionisation potential of H2O, i.e. charge transfer cannot occur Which otherwise would result in ions that can react efficiently with water (e.g. H2O + H2O -> H3O+ + OH) leading to H3O+ becoming the dominant reagent ion. Reaction processes observed are non-dissociative charge transfer (O-2(+) with TNT and TNB), dissociative charge transfer (O-2(+) with TNT) and adduct formation (NO+ with PETN and RDX). O-2(+) is found to be unreactive with PETN and RDX, and under the conditions operating in the reaction region of the PTR-MS only a low signal associated with NO' TNT was observed. No NO+.TNB was detected. (C) 2013 Elsevier B.V. All rights reserved.

Fears of terrorist attacks have led to the development of various technologies for the real-time detection of explosives, but all suffer from potential ambiguities in the assignment of threat agents. Using proton transfer reaction mass spectrometry (PTR-MS), an unusual bias dependence in the detection sensitivity of 2,4,6 trinitrotoluene (TNT) on the reduced electric field (E/N) has been observed. For protonated TNT, rather than decreasing signal intensity with increasing E/N, which is the more usual sensitivity pattern observed in PTR-MS studies, an anomalous behavior is first observed, whereby the signal intensity initially rises with increasing E/N. We relate this to unexpected ion-molecule chemistry based upon comparisons of measurements taken with related nitroaromatic compounds (1,3,5 trinitrobenzene, 1,3 dinitrobenzene, and 2,4 dinitrotoluene) and electronic structure calculations. This dependence provides an easily measurable signature that can be used to provide a rapid highly selective analytical procedure to minimize false positives for the detection of TNT. This has major implications for Homeland Security and, in addition, has the potential of making instrumentation cost-effective for use in security areas. This study shows that an understanding of fundamental ion-molecule chemistry occurring in low-pressure drift tubes is needed to exploit selectivity and sensitivity for analytical purposes.

The first reported use of proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) for the detection of a range of illicit and prescribed drugs is presented here. We describe the capabilities of PTR-TOF-MS to detect the following commonly used narcotics-ecstasy (N-methyl-3,4-methylenedioxyamphetamine), morphine, codeine, cocaine and heroin-by the direct sampling of the headspace above small solid quantities (approximately 50 mg) of the drugs placed in glass vials at room temperature, i.e. with no heating of the sample and no pre-concentration. We demonstrate in this paper the ability to identify the drugs, both illicit and prescribed, using PTR-TOF-MS through the accurate m/z assignment of the protonated parent molecule to the second decimal place. We have also included in this study measurements with an impure sample of heroin, containing typical substances found in "street" heroin, to illustrate the use of the technology for more "real-world" samples. Therefore, in a real-world complex chemical environment, a high level of confidence can be placed on the detection of drugs. Although the protonated parent is observed for all drugs, the reactant channel leading to this species is not the only one observed and neither is it necessarily the most dominant. Details on the observed fragmentation behaviour are discussed and compared to electrospray ionisation MS(n) studies available in the literature.

In this paper we report an investigation of the effects of E/N over the range of 90-140Td on the product ions resulting from the reactions of H3O+ with 12 saturated alcohols using a proton transfer reaction mass spectrometer (PTR-MS). The alcohols included in this study are methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl-1-propanol, 2-methyl-2-propanol, 2-butanol, cyclopentanol, 1-pentanol, cyclohexanol, and 1-hexanol. Only in the cases of methanol and ethanol are any substantial amounts of the protonated parent observed at any E/N. For the other saturated alcohols predominantly fragment ions are observed. This implies that attempts to identify and hence monitor saturated alcohols in trace concentrations in a complex chemical environment using PTR-MS will be fraught with difficulties because a given m/z will not be unique to a particular chemical compound, i.e., multiple species could be present at a given m/z. In addition to changes in E/N we present preliminary results with regards to changing the conditions in the generation of the reagent ions via altering the operational conditions within the ion source (a hollow cathode). We present product ion branching ratios as a function of hollow cathode emission current for cyclohexanol, 1-propanol and 2-propanol at fixed E/N. Although not part of the reaction chamber, we have found that changing the hollow cathode emission current results in modifications to the product ion branching ratios. We presume that these observed changes are a result of altering the internal energies of the reagent ions and thereby modify the reaction kinetics and dynamics occurring within the drift tube of a PTR-MS. (C) 2010 Elsevier B.V. All rights reserved.

This work demonstrates for the first time the potential of using recent developments in proton transfer reaction mass spectrometry for the rapid detection and identification of chemical warfare agents (CWAs) in real-time. A high-resolution (m/Deltam up to 8000) and high-sensitivity (approximately 50 cps/ppbv) proton transfer reaction time-of-flight mass spectrometer (PTR-TOF 8000 from Ionicon Analytik GmBH) has been successfully used to detect a number of CWA simulants at room temperature; namely dimethyl methylphosphonate, diethyl methylphosphonate, diisopropyl methylphosphonate, dipropylene glycol monomethyl ether and 2-chloroethyl ethyl sulfide. Importantly, we demonstrate in this paper the potential to identify CWAs with a high level of confidence in complex chemical environments, where multiple threat agents and interferents could also be present in trace amounts, thereby reducing the risk of false positives. Instantaneous detection and identification of trace quantities of chemical threats using proton transfer reaction mass spectrometry could form the basis for a timely warning system capability with greater precision and accuracy than is currently provided by existing analytical technologies.

The synthesis of fifteen phosphylated compounds having P─OCD3, P─CD3, or P─OCD2CH3 groups is described. Selective chemistry for the precise placement of the deuterated groups was devised, and the products were isolated in a high purity in generally good yields. The compounds were required to study their behavior after electrospray ionization in an ion trap mass spectrometer.

The thermal bimolecular rate coefficients and product ion branching ratios for the reactions of the positive ions (in order of increasing recombination energy) H2O+, N2O+, O+, CO2+, CO+, N+, and N2+ with the bromine containing molecules CF3Br, CF2Br2, CFBr3, CF2BrCl, CFBr2Cl, CBrCl3, CH3Br, CH2Br2, CH2FBr, CHF2Br, CHFBr2, CH2BrCl, CHBrCl2, CHBr2Cl, CF3CF2Br, and CF2BrCF2Br at 300K are reported. This represents the most comprehensive investigation of the positive ion chemistry of brominated molecules to date, with nearly all of the experimental data being presented here for the first time. Also reported in this paper are the reactions of H2O+ with CH3CH2Br, CH2BrCH2Cl, and CH2BrCH2Br. All the reactions are efficient, with the experimental reaction rate coefficients being greater than 10−9cm3molecule−1s−1. Dissociative charge transfer is considered to be the dominant reaction mechanism.

The thermal bimolecular rate coefficients and product ion branching ratios for the reactions of H3O+ with the bromine containing molecules CH3Br, CH2Br2, CH2FBr, CHF2Br, CHFBr2, CH2BrCl, CHBrCl2, CHBr2Cl, CH3CH2Br, CH2BrCH2Cl, CH2BrCH2Br, CF3CF2Br and CF2BrCF2Br at 300K are reported. H3O+ reacts with an experimental rate coefficient (kexp) close to the collisional value (kc≈10−9cm3molecule−1s−1) with CHFBr2, CHBrCl2, CHBr2Cl, CH2BrCH2Cl, and CH2BrCH2Br, at a decreased efficiency with CH3CH2Br (kexp/kc≈0.3). The other neutral reactant molecules, CH3Br, CH2FBr, CHF2Br, CF3CF2Br, and CF2BrCF2Br react through a three-body associative process. There is no observable reaction with CH2Br2 and CH2BrCl. Mechanistic arguments are given that go some way to explaining the observed range in both reactivity and reaction pathways.

The reaction rate coefficients and ion products for the gas-phase reactions of O2−, O−, OH−, CF3−, and F− with trichloroethene (CCl2CHCl), 1,1-dichloroethene (CH2CCl2), and Z (cis) and E (trans)-1,2-dichloroethene (CHClCHCl) are presented. With the exception of CCl2CHCl, the O2− bimolecular reaction rate coefficients are substantially below the collisional values. All the other anions react with the molecules with rate coefficients at or close to (within a factor of two) the corresponding collisional values. The experimental results are interpreted in terms of pathways initiated by nucleophilic attack on carbon or by proton abstraction. Proton abstraction is an exothermic channel for the reactions of O−, OH−, CF3−, and F− with each of the three isomers of dichloroethene, but C2HCl2− was only directly observed for E-CHClCHCl. Orbital overlap arguments provide the explanation of this observation.

In this paper we report the reactions of O− and O2− with several saturated hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) in a 0.5 Torr helium buffer gas at about 300 K using a selected ion flow tube. The reaction rate coefficients and branching ratios determined for the large number of reactions studied are presented. O− is found to react with all the molecules studied, and several distinct reaction processes are observed. These include nucleophilic attack on chlorine, nucleophilic attack on carbon, and hydrogen, proton, and H2+ abstraction. Nucleophilic attack on carbon is found to dominate the O2− reactions with the HCFCs. Bimolecular reactions of O2− with the HFCs do not occur.

The bimolecular rate coefficients and ion products for the reactions of H3O+ and H2O+ with the bromine-containing molecules CF3Br, CF2Br2, CF2BrCl, CFBr3, CFBr2Cl, and CBrCl3 at 300 K are reported. With the exception of the reactions of H3O+ with CF3Br and CF2BrCl, the rate coefficients are near the collisional values (k approximate to 10(-9) cm(3) molecule(-1) s(-1)). The most efficient exit pathway for the majority of the H3O+ reactions is the formation of a trihalomethyl cation, together with water and a hydrogen halide as the neutral products. In each case, more than one trihalomethyl cation can be formed. The branching ratios are largest for the products resulting from the breaking of a C-F bond. This is attributed to the high bond strength of HF relative to HCl and HBr. Similarly for CBrCl3, the major product cation is CCl2Br+. The H2O+ reactions are found to proceed predominantly via charge transfer. For the reaction of H2O+ with CF3Br there is clear evidence for intimate reaction pathways in which bonds are broken and formed.

An ion mobility spectrometer (IMS), operating in air in the negative ion mode, has been shown to have potential for detecting and monitoring perfluoroisobutene (PFIB), a toxic perfluorocarbon and potential industrial hazard. Complex spectra with a variety of product ions are observed. Most of these ions result from reactions of PFIB with the negative reactant ions although some important product ions (particularly at high PFIB concentrations) are attributed to reactions with reactive transient species (including electrons) in the ionization region of the IMS system. The ions have been identified using mass spectrometry and a wide variety of isotopic tracers. The results of our parallel studies using a selected ion flow tube have been included where appropriate.

Rate coefficients and branching ratios have been measured for the reactions of O− and O2− with CCl4, CCl3F, CCl2F2, CClF3, CF4, CHCl3, CH2Cl2, and CH3Cl using a selected ioin flow tube at 300 K and 0.6 Torr. Measured rate coefficients for all reactions (except for O−2/CClF3 and O−2 and O−/CF4 which do not react) are at or close to the collisional rate. Where electron transfer is exoergic it is observed for the chlorofluoromethanes but not for the chloromethanes. It is suggested that nucleophilic attack of O− and O−2 on both chlorine and carbon (in the case of the chlorofluoromethanes) and on chlorine, carbon and hydrogen (in the case of the chloromethanes) are required to produce the observed products. It is also suggested that, with the exception of methyl chloride, the halide ion, X− (X = Cl or F), is not formed directly, but by the decomposition of ClX− which is formed with excess vibrational energy. Following a discussion of the relevance of our results to the effects of oxygen doping upon the response of an electron capture detector (ECD) to halocarbon, it is concluded that the currently accepted mechanism to explain the observed increased sensitivity of the ECD is partially in error.