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A selected ion flow-drift tube mass spectrometric analytical technique, SIFDT-MS, is described that extends the established selected ion flow tube mass spectrometry, SIFT-MS, by the inclusion of a static but variable E-field along the axis of the flow tube reactor in which the analytical ion-molecule chemistry occurs. The ion axial speed is increased in proportion to the reduced field strength E/N (N is the carrier gas number density), and the residence/reaction time, t, which is measured by Hadamard transform multiplexing, is correspondingly reduced. To ensure a proper understanding of the physics and ion chemistry underlying SIFDT-MS, ion diffusive loss to the walls of the flow-drift tube and the mobility of injected H3O(+) ions have been studied as a function of E/N. It is seen that the derived diffusion coefficient and mobility of H3O(+) ions are consistent with those previously reported. The rate coefficient has been determined at elevated E/N for the association reaction of the H3O(+) reagent ions with H2O molecules, which is the first step in the production of H3O(+)(H2O)1,2,3 reagent hydrate ions. The production of hydrated analyte ion was also experimentally investigated. The analytical performance of SIFDT-MS is demonstrated by the quantification of acetone and isoprene in exhaled breath. Finally, the essential features of SIFDT-MS and SIFT-MS are compared, notably pointing out that a much lower speed of the flow-drive pump is required for SIFDT-MS, which facilitates the development of smaller cost-effective analytical instruments for real time breath and fluid headspace analyses.

The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls.The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies.A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs.Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal-were present at significantly higher concentrations (P 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ± 0.01 and 0.87 ± 0.03, respectively.Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.

Highlights • An integrated electrochemical platform was manufactured by bi-material 3D printing. • It was applied to investigate the reaction between hydrazine and carbon dioxide. • Experimental results were supported by finite-element method numerical simulations., The combination of computer assisted design and 3D printing has recently enabled fast and inexpensive manufacture of customized ‘reactionware’ for broad range of electrochemical applications. In this work bi-material fused deposition modeling 3D printing is utilized to construct an integrated platform based on a polyamide electrochemical cell and electrodes manufactured from a polylactic acid-carbon nanotube conductive composite. The cell contains separated compartments for the reference and counter electrode and enables reactants to be introduced and inspected under oxygen-free conditions. The developed platform was employed in a study investigating the electrochemical oxidation of aqueous hydrazine coupled to its bulk reaction with carbon dioxide. The analysis of cyclic voltammograms obtained in reaction mixtures with systematically varied composition confirmed that the reaction between hydrazine and carbon dioxide follows 1/1 stoichiometry and the corresponding equilibrium constant amounts to (2.8 ± 0.6) × 103. Experimental characteristics were verified by results of numerical simulations based on the finite-element-method., Graphical abstract Image, graphical abstract

Atmospheric concentrations of isoprene (2-methylbutadiene) in environmental research and in exhaled breath for medical research are usually measured by soft chemical ionization mass spectrometry that relies on a knowledge of the kinetics of the gas phase reactions of H

Rationale Oxidative stress of cell membranes leads to a number of pathological processes associated with some diseases and is accompanied by the release of volatile aldehydes, which, potentially, can be used as biomarkers. Thus, the aim was to investigate peroxidation of defined synthetic membranes by direct quantitative analysis of volatile aldehydes. Methods The concentration spectra of volatile compounds present in the headspace of synthetic membranes under peroxidation stress and following mechanical stress due to sonication were obtained using solid phase microextraction (SPME) in combination with Gas Chromatography Mass Spectrometry (SPME/GC/MS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS). The focus was on the direct, real time quantification of volatile aldehydes. In addition, the total aldehydes in the aqueous membrane suspensions were quantified using the TBARS method. Results Propanal, butanal, pentanal, hexanal, heptanal and malondialdehyde were detected and quantified in the humid headspace of the media containing the synthetic membranes following peroxidation. The composition and concentration of these saturated aldehydes strongly depend on the unsaturated fatty acids representation in the liposomes. Some protective effect of cholesterol was observed especially for membranes peroxidised by Fenton reagents and after application of a mechanical stress. Conclusions This study demonstrates that peroxidation of model synthetic membranes in vitro can be tracked in real time using direct quantification by SIFT-MS of several specific aldehydes in the headspace of the membrane suspensions. Cholesterol plays an important role in retaining membrane structure and can indirectly protect membranes from lipid peroxidation.

Rationale Selected ion flow tube mass spectrometry, SIFT-MS, used for trace gas analyses has certain fundamental limitations that could be alleviated by adding a facility that allows reaction times and ion interaction energies to be varied. Thus, a selected ion flow-drift tube, SIFDT, has been created to explore the influence of an embedded electric field on these parameters and on reaction processes. Methods The new SIFTD instrument was constructed using a miniature resistive glass drift tube. Arrival times of ions, t, analysed by a downstream quadrupole mass spectrometer over the m/z range 10–100 were studied by modulating the injected ion current using a gate lens. Single pulse modulation was compared with pseudorandom time multiplexing exploiting the Hadamard transformation. A simple model involving analysis of ethanol and water vapour mixture in air was used to explore the advantages of the SIFDT concept to SIFT-MS analysis. Results It is shown that the resistive glass drift tube is suitable for SIFDT experiments. The Hadamard transformation can be used to routinely determine reagent ion residence time in the flow-drift tube and also to observe differences in arrival times for different product ions. Two-dimensional data combining arrival time and mass spectra can be obtained rapidly. The calculated ion drift velocities vary with the reduced field strength, E/N, and the calculated ion mobilities agree with theoretical and previous literature values. Conclusions This study has provided evidence that the SIFDT-MS technique can be implemented in a miniature and low-cost instrument and two- or three-dimensional data can be obtained (product ion count rates as functions of m/z, t and E/N) using the Hadamard transformation thus providing exciting possibilities for further analytical additions and extensions of the SIFT-MS technique. Copyright © 2015 John Wiley & Sons, Ltd.

Rationale It has been proposed that malondialdehyde (MDA) reflects free oxygen-radical lipid peroxidation and can be useful as a biomarker to track this process. For the analysis of MDA molecules in humid air by selected ion flow tube mass spectrometry (SIFT-MS), the rate coefficients and the ion product distributions for the reactions of the SIFT-MS reagent ions with volatile MDA in the presence of water vapour are required. Methods The SIFT technique has been used to determine the rate coefficients and ion product distributions for the reactions of H3O+, NO+ and O2+• with gas-phase MDA. In support of the SIFT-MS analysis of MDA, solid-phase microextraction, SPME, coupled with gas chromatography/mass spectrometry, GC/MS, has been used to confirm the identification of MDA. Results The primary product ions have been identified for the reactions of H3O+, NO+ and O2+• with MDA and the formation of their hydrates formed in humid samples is described. The following combinations of reagent and the analyte ions (given as m/z values) have been adopted for SIFT-MS analyses of MDA in the gas phase: H3O+: 109; NO+: 89, 102; O2+•: 72, 90, 108, 126. The detection and quantification of MDA released by a cell culture by SIFT-MS are demonstrated. Conclusions This detailed study has provided the kinetics data required for the SIFT-MS analysis of MDA in humid air, including exhaled breath and the headspace of liquid-phase biogenic media. The detection and quantification by SIFT-MS of MDA released by a cell culture are demonstrated. Copyright © 2015 John Wiley & Sons, Ltd.

Flow tube reactors coupled with quantitative mass spectrometry have made, and continue to make, major contributions to gas phase ion–molecule chemistry, to recombination and electron attachment studies and, most recently, to gas phase trace gas analysis. This paper briefly reviews the concepts and principles of operation of flowing afterglow, FA, and flowing afterglow Langmuir probe, FALP, plasma reactors, and selected ion flow tube, SIFT, ion swarm reactors for the study of the above processes. This paved the way to our recent developments of the novel analytical methods that we call selected ion flow tube mass spectrometry, SIFT-MS, and flowing afterglow mass spectrometry, FA-MS. A time line of these developments during the last fifty years is presented. It is shown how exploitation of FA and SIFT has provided the essential kinetics data that allow modelling of the ion chemistry of naturally occurring plasmas, especially the terrestrial ionosphere and interstellar gas clouds, and has greatly facilitated the developments and evolution of SIFT-MS and FA-MS, which are contributing to the science of ambient trace gas analysis. The wide ranging applications of SIFT-MS are alluded to whilst focusing on the successful direct real time quantitative analysis of volatile metabolites in exhaled breath forcibly demonstrating the unique analytical features of SIFT-MS.

There is interest in the development of exhaled breath tests for the detection of lower airway infection in children with cystic fibrosis. The first stage of this process is the identification of volatile organic compounds (VOCs) released into the gas phase by CF pathogens that can be used as breath test biomarkers. Selected ion flow tube mass spectrometry (SIFT-MS) is ideally suited to these in vitro studies as it allows simultaneous quantification of multiple VOCs in real time. We review a decade of in vitro experiments using SIFT-MS to analyse the VOCs released by respiratory pathogens. This includes identification and quantification of VOCs and the investigation of the in vitro factors that affect their production. We also report on how our culture methodology has been refined over the years to better account for variations in bacterial mass. Finally, we discuss how these in vitro findings have been translated into clinical trials and assess possible future applications.

Studies have been carried out of the compounds generated from heated “street” cannabis in the commercial device known as the “Volcano” using the selected ion flow tube mass spectrometry (SIFT-MS) analytical method. Such vaporising devices are preferred for the delivery of the cannabis active ingredients for pain relief and therapeutic purposes since they remove from the smoke the harmful high molecular weight compounds such as tars and polycyclic aromatic hydrocarbons. Whilst it is known that smoking cannabis is associated with adverse health effects, little is known about risks of its inhalation of volatile compounds from vaporizers. In the present study, the concentrations of the volatile lower molecular weight compounds ammonia, methanol, acetic acid, methyl acetate, monoterpenes and sesquiterpenes present in the trapped air/vapour volume of the “Volcano” have been determined directly by SIFT-MS obviating sample collection/pre-concentration and delayed off-line analysis as used by most other analytical techniques. The concentrations of these compounds are compared to the tetrahydrocannabinol (THC; expected to be largely Δ-9-THC) content of the cannabis plant material as assayed using standard extraction/derivatisation/GC-MS analysis. The observed high concentrations of ammonia were strongly correlated with the THC which is largely contained in the buds of the cannabis plant, whereas the identified volatile organic compounds were predominantly released by the leaves. Whilst the “Volcano” device removes some toxic compounds from the smoke and reduces their inhalation by its user, it likely leads to enhanced ingestion of toxic ammonia known to result in neurobehavioral impairment.

The reactions of H

Much effort continues to be devoted to the development of devices to analyse breath ammonia with the anticipation that breath ammonia analyses will be useful in clinical practice. In this perspective we refer to the analytical techniques that have been used to measure breath ammonia, focusing on selected ion flow tube mass spectrometry, SIFT-MS, of which we have special knowledge and understanding. From the collected data obtained using the different techniques, we exam the origins of mouth- and nose-exhaled ammonia and conclude that mouth-exhaled ammonia is always elevated above a concentration that would be equilibrated with blood ammonia and is largely produced by the action of enzymes on salivary urea. Support to this conclusion is given by the reasonable correlation between blood urea concentration and mouth-exhaled ammonia concentration. Further, it is discussed that nose-exhaled ammonia largely originates at the alveolar interface and so its concentration more closely relates to the expected alveolar blood ammonia concentration. Ingestion of proteins results in increased blood/saliva urea and ultimately mouth-exhaled ammonia as does the generation of urease by H. pylori infection. It is also concluded that when mouth-exhaled ammonia is elevated then it may be due to either abnormally high blood urea, a high pH of the saliva/mouth/airways mucosa, poor oral hygiene or a combinations of these.

A study has been carried out on the volatile organic compounds (VOCs) in the exhaled breath of patients suffering from inflammatory bowel disease (IBD), comprising 136 with Crohn's disease (CD) and 51 with ulcerative colitis (UC), together with a cohort of 14 healthy persons as controls. Breath samples were collected by requesting the patients to inflate Nalophan bags, which were then quantitatively analysed using selected ion flow tube mass spectrometry (SIFT-MS). Initially, the focus was on n-pentane that had previously been quantified in single exhalations on-line to SIFT-MS for smaller cohorts of IBD patients. It was seen that the median concentration of pentane was elevated in the bag breath samples of the IBD patients compared to those of the healthy controls, in accordance with the previous study. However, the absolute median pentane concentrations in the bag samples were about a factor of two lower than those in the directly analysed single exhalations-a good illustration of the dilution of VOCs in the samples of breath collected into bags. Accounting for this dilution effect, the concentrations of the common breath VOCs, ethanol, propanol, acetone and isoprene, were largely as expected for healthy controls. The concentrations of the much less frequently measured hydrogen sulphide, acetic acid, propanoic acid and butanoic acid were seen to be more widely spread in the exhaled breath of the IBD patients compared to those for the healthy controls. The relative concentrations of pentane and these other VOCs weakly correlate with simple clinical activity indices. It is speculated that, potentially, hydrogen sulphide and these carboxylic acids could be exhaled breath biomarkers of intestinal bacterial overgrowth, which could assist therapeutic intervention and thus alleviate the symptoms of IBD.

It is argued that shortcomings of certain approaches to breath analysis research based on superficial interpretation of non-quantitative data are inadvertently inhibiting the progression of non-invasive breath analysis into clinical practice. The objective of this perspective is to suggest more clinically profitable approaches to breath research. Thus, following a discourse on the challenges and expectations in breath research, a brief indication is given of the analytical techniques currently used for the analysis of very humid exhaled breath. The seminal work that has been carried out using GC-MS revealed that exhaled breath comprises large numbers of trace volatile organic compounds, VOCs. Unfortunately, analysis of these valuable GC-MS data is mostly performed using chemometrics to distinguish the VOC content of breath samples collected from patients and healthy controls, and reliable quantification of the VOCs is rarely deemed necessary. This limited approach ignores the requirements of clinically acceptable biomarkers and misses the opportunity to identify relationships between the concentrations of individual VOCs and certain related physiological or metabolic parameters. Therefore, a plea is made for more effort to be directed towards the positive identification and accurate quantification of individual VOCs in exhaled breath, which are more physiologically meaningful as best exemplified by the quantification of breath nitric oxide, NO. Support for the value of individual VOC quantification is illustrated by the SIFT-MS studies of breath hydrogen cyanide, HCN, a biomarker of Pseudomonas aeruginosa infection, breath acetic acid as an indicator of airways acidification in cystic fibrosis patients, and n-pentane as a breath biomarker of inflammation in idiopathic bowel disease patients. These single VOCs could be used as non-invasive monitors of the efficacy of therapeutic intervention. The increase of breath methanol following the ingestion of a known amount of the sweetener aspartame impressively shows that accurate breath analysis is a reliable indicator of blood concentrations. However, using individual VOCs for specific disease diagnosis does have its problems and it is, perhaps, more appropriate to see their concentrations as proxy markers of general underlying physiological change. We dedicate this perspective to Lars Gustafsson for his seminal work on breath research and especially for his pioneering work on nitric oxide measurements in exhaled breath in asthma, which best shows the utility and value of the quantification of individual breath biomarkers on which this perspective focuses.

A selected ion flow tube, SIFT, study has been carried out of the reactions of H 3 O + , NO + and O 2 + with four carboxylic acids: formic acid, acetic acid, propionic acid and butyric acid. Ethanol was also included in order to provide data that could facilitate SIFT-MS analyses of formic acid in its presence. The product ion branching ratios of the primary reactions were obtained and compared with the already known values, thus improving the certainty of kinetic data for quantification of these compounds. The primary products of the H 3 O + reactions, the protonated molecules MH + , and the primary products of the NO + reactions, nitrosonated (MNO + ) and dehydroxidated (M−OH) + molecules, are observed to react with the molecules of water by three body association. Original data were obtained for the kinetics of these cluster-forming reactions. The three body rate constant for the associations of MH + with H 2 O in He have been determined in the units of 10 −27 cm 3 s −1 for formic, acetic, propionic and butyric acids as 1.4, 2.4, 3.8 and 4.9, respectively . The three body rate constant for the associations of MNO + with H 2 O in He were obtained in the same units as 2.1, 1.1, 0.15 and 0.7. Results will improve the certainty of identification and accuracy of quantification of vapors of carboxylic acids by SIFT-MS in medical and food science research.

The octanol–water partition coefficient, KOW, of 2-heptenal, 2-octenal, 2-nonenal, 2-nonanone and octanal was obtained from headspace vapour concentrations in a bubble column determined by selected ion flow tube mass spectrometry (SIFT-MS) with and without addition of 1-octanol to the water solution. Experimental values for log KOW at 299 K range from 2.06 ± 0.12 (2-heptenal) to 2.31 ± 0.14 (1-octanal). Partition enthalpies, −Δ0Hw→o, of 19.9 ± 6.2 kJ mol−1 (1-octanal) up to 118.1 ± 8.5 kJ mol−1 (2-nonanone) were obtained. In conjunction to the determination of KOW, Henry's law coefficients of (2.76 ± 0.38) × 10−3 molg moll mg−3 ml3 for 2-heptenal to (2.79 ± 0.16) × 10−2 molg moll mg−3 ml3 for 1-octanal were experimentally obtained.

A novel, non-invasive technique is reported for determining the numbers of cells in a culture by quantifying dimethyl sulphide (DMS) in the culture headspace as produced by the cellular enzymatic reduction of dissolved dimethyl sulphoxide (DMSO). Measured DMS concentrations, as performed using selected ion flow tube mass spectrometry (SIFT-MS), in the headspace of 2D and 3D cultures of four cell lines, viz. HEK293 (kidney), MG63 (bone), hepG2 (liver) and CALU-1 (lung), linearly correlate with starting cell number. Clear differences in the rates of production of DMS by the four cell types in both the 2D and 3D situations are seen. This novel analytical technique for cell enumeration offers a significant contribution to quality assessment across cell-based research and industry, including analysis of large scale culture systems, and for routine cell biology research.

Following our recent in vitro study of the volatile compounds emitted into the gas phase by the respiratory pathogens Pseudomonas aeruginosa (PA), and most recently Staphylococcus aureus (SA), Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI), we have extended this work to the investigation of the volatile compounds emitted by in vitro cultures of the common respiratory fungus Aspergillus fumigatus (AF). The measurements were achieved using selected ion flow tube mass spectrometry (SIFT-MS) by which real time analyses of trace volatile compounds can be achieved without disturbing the cultures. It is seen that copious amounts of ammonia and the organosulphur compounds methanethiol, dimethyl sulphide and dimethyl disulphide are produced by AF cultures. These may be sufficient to allow for non-invasive detection of the AF in the airways of infected patients by breath analysis. AF also efficiently absorbs and metabolises the aldehydes acetaldehyde, butanal and pentanal from the supportive medium (brain-heart infusion broth). Preliminary studies of the volatile compounds emitted by co-cultures of AF with PA, SA and SP revealed that the biomarker HCN (for PA) is not compromised by the presence of AF, and the organosulphur compounds (for AF) are not compromised by the presence of SA or SP.

The major features of the selected ion flow tube mass spectrometry (SIFT-MS) analytical method that was conceived and designed for the analysis, in real time, of air obviating sample collections into bags or extraction by pre-concentration of trace compounds onto surfaces are reviewed. The unique analytical capabilities of SIFT-MS for ambient analysis are stressed that allow quantification of volatile organic and inorganic compounds directly from the measurement of physical parameters without the need for regular instrumental calibration using internal or external standards. Then, emphasis is placed on the challenging real-time accurate analysis of single exhalations of humid breath, which is now achieved and readily facilitates wider applications of SIFT-MS in other fields where trace gas analysis has value. The quality of the data obtained by SIFT-MS is illustrated by the quantification of some exhaled breath metabolites that are of immediate relevance to physiology and medicine, including that of hydrogen cyanide in the breath of patients with cystic fibrosis. The current status of SIFT-MS is revealed by a form of a strengths, weakness, opportunities and threats (SWOT) analysis intended to present an objective view of this analytical technique and the likely way forward towards its further development and application.

RATIONALE Inflammatory bowel disease has a relatively large incidence in modern populations and the current diagnostic methods are either invasive or have limited sensitivity or specificity. Thus, there is a need for new non-invasive methods for its diagnosis and therapeutic monitoring, and breath analysis represents a promising direction in this area of research. Specifically, a method is needed for the absolute quantification of pentane in human breath. METHODS Selected ion flow tube mass spectrometry (SIFT-MS) has been used to study the kinetics of the O2+ reaction with pentane. Product ions at m/z 42 and 72 were chosen as characteristic ions useful for the quantification of pentane and the reactivity of these ions with water vapour was characterized. A pilot study has been carried out of pentane in the exhaled breath of patients with Crohn's disease (CD) and ulcerative colitis (UC) and of healthy volunteers. RESULTS Accurate data on the kinetics of the gas phase reaction of the O2+• ions with pentane have been obtained: rate coefficient 8 × 10–10 cm3 s–1 (±5%) and branching ratios into the following product ions C5H12+• (m/z 72, 31%); C4H9+ (m/z 57, 8%); C3H7+ (m/z 43, 40%), C3H6+• (m/z 42, 21%). A method of calculation of absolute pentane concentration in exhaled breath was formulated using the count rates of the ions at m/z 32, 42, 55 and 72. Pentane was found to be significantly elevated in the breath of both the CD (mean 114 ppbv) and the UC patients (mean 84 ppbv) relative to the healthy controls (mean 40 ppbv). CONCLUSIONS SIFT-MS can be used to quantify pentane in human breath in real time avoiding sample storage. This method of analysis can ultimately form the basis of non-invasive screening of inflammatory processes, including inflammatory bowel disease. Copyright © 2013 John Wiley & Sons, Ltd.

8 pages, 4 tables, 2 figures.-- Available online 29 June 2012, The objective of this work was to evaluate the use of a direct analysis technique (SIFT-MS) to measure the lipid oxidation process in beef meat packed under high oxygen atmosphere and compare it to conventional techniques such as gas chromatography–mass spectrometry analysis and TBARS values. Meat samples from two suppliers were selected and packaged under the same atmosphere conditions. The fatty acid content, the physicochemical (TBARS and volatile compounds) and sensory parameters were measured. The samples from supplier 2 had a highest content of PUFA and n6 fatty acids that was related with a highest oxidation during storage. SIFT-MS and SPME-GC–MS detected a significant increase for most of the volatiles compounds analyzed during storage especially, in aldehyde compounds. High correlation coefficients between TBARS values and linear aldehydes (C3–C7) measured by both techniques were obtained and this indicates that SIFT-MS can be used to monitor lipid oxidation changes., Financial support from MINECO (Spain) and Academy of Science of the Czech Republic for the joint project (project number 2010CZ0011) are fully acknowledged. Partial funding from AGL 2009-08787 from MINECO (Spain), Prometeo 2012-001 (GVA) and FEDER funds and by Grant Agency of the Czech Republic (projects number 203/09/P172 and 203/09/0256) are also gratefully acknowledged.

Alcohols are often present in foods and other biological media, including exhaled breath, urine and cell culture headspace. For their analysis by selected ion flow tube mass spectrometry (SIFT-MS), the ion chemistry initiated by the reactions of the reagent ions HThe reactions of HThe HThis detailed study has provided the kinetics data, including the secondary hydrated ion product distributions, for the reactions of a number of volatile primary alcohols with the SIFT-MS reagent ions H

Large-scale plasma was created in gas mixtures containing methane using high-power laser-induced dielectric breakdown (LIDB). The composition of the mixtures corresponded to a cometary and/or meteoritic impact into the early atmosphere of either Titan or Earth. A multiple-centimeter-sized fireball was created by focusing a single 100 J, 450 ps near-infrared laser pulse into the center of a 15 L gas cell. The excited reaction intermediates formed during the various stages of the LIDB plasma chemical evolution were investigated using optical emission spectroscopy (OES) with temporal resolution. The chemical consequences of laser-produced plasma generation in a CH4–N2–H2O mixture were investigated using high resolution Fourier-transform infrared absorption spectroscopy (FTIR) and gas selected ion flow tube spectrometry (SIFT). Several simple inorganic and organic compounds were identified in the reaction mixture exposed to ten laser sparks. Deuterated water (D2O) in a gas mixture was used to separate several of the produced isotopomers of acetylene, which were then quantified using the FTIR technique.

Non-invasive breath analysis has been used to search for volatile biomarkers of lungs and airways infection by Pseudomonas aeruginosa, PA, in cystic fibrosis patients. The exhaled breath of 20 PA-infected patients and 38 PA-negative patients was analysed using selected ion flow tube mass spectrometry, SIFT-MS. Special attention was given to the positive identification and accurate quantification of 16 volatile compounds (VOCs) as assured by the detailed consideration of their analytical ion chemistry occurring in the SIFT-MS reactor. However, the diagnostic sensitivity and specificity of the concentrations of any of the 16 compounds taken individually were found to be low. But when a linear combination of the concentrations of all 16 VOCs was used to construct an optimised receiver operating characteristics (ROC) curve using a linear logistic model, the diagnostic separation of PA-infected patients relative to the PA-negative patients was apparently good in terms of the derived sensitivity (89%), specificity (86%), and the area under the ROC curve is 0.91. Four compounds were revealed by the linear logistic model as significant, viz. malondialdehyde, isoprene, phenol and acetoin. The implications of these results to PA detection in the airways are assessed. Whilst such a metabolomics approach to optimise the ROC curve is widely used in breath analysis, it can lead to misleading indications. Therefore, we conclude that the results of the linear logistic model analyses are of limited immediate clinical value. The identified compounds should rather be considered as a stimulus for further independent studies involving larger patient cohorts.

As a contribution to the continuing search for breath biomarkers of lung and airways infection in patients with cystic fibrosis, CF, we have analysed the volatile metabolites released in vitro by Pseudomonas aeruginosa and other bacteria involved in respiratory infections in these patients, i.e. those belonging to the Burkholderia cepacia complex, Staphylococcus aureus or Stenotrophomonas maltophilia. These opportunistic pathogens are generally harmless to healthy people but they may cause serious infections in patients with severe underlying disease or impaired immunity such as CF patients. Volatile organic compounds emitted from the cultures of strains belonging to the above-mentioned four taxa were analysed by selected ion flow tube mass spectrometry. In order to minimize the effect of differences in media composition all strains were cultured in three different liquid media. Multivariate statistical analysis reveals that the four taxa can be well discriminated by the differences in the headspace VOC concentration profiles. The compounds that should be targeted in breath as potential biomarkers of airway infection were identified for each of these taxa of CF pathogens.

This article reflects our observations of recent accomplishments made using selected ion flow tube MS (SIFT-MS). Only brief descriptions are given of SIFT-MS as an analytical method and of the recent extensions to the underpinning analytical ion chemistry required to realize more robust analyses. The challenge of breath analysis is given special attention because, when achieved, it renders analysis of other air media relatively straightforward. Brief overviews are given of recent SIFT-MS breath analyses by leading research groups, noting the desirability of detection and quantification of single volatile biomarkers rather than reliance on statistical analyses, if breath analysis is to be accepted into clinical practice. A ‘strengths, weaknesses, opportunities and threats’ analysis of SIFT-MS is made, which should help to increase its utility for trace gas analysis.

Soft chemical ionisation techniques including selected ion flow tube mass spectrometry, SIFT-MS, and proton transfer reaction mass spectrometry, PTR-MS, cannot currently quantify individual isomers present simultaneously in samples, a notable example being atmospheric monoterpenes. A possible solution lies in integrating in-tube collision-induced dissociation, CID, into a selected ion flow-drift tube mass spectrometry, SIFDT-MS, instrument.In-tube CID was implemented by applying electrostatic potential difference between the resistive glass flow-drift tube downstream end and the nose cone of a quadrupole mass spectrometer. The resulting inhomogeneous electric field accelerates the product ions along the last 1 mm before the nose cone and causes their dissociation in collisions with molecules of the buffer gas (4% air, 96% helium, 2 mbar). Mass spectra of the product ions of NO(+) reactions with 3-carene, β-pinene, (S)-limonene and their mixture were obtained for variable potential difference.Potential difference up to 47.7 V resulted in dramatic changes in the mass spectra due to fragmentation of the monoterpene radical molecular cations. The main observed fragments correspond to logical losses from different isomeric structures. Fragmentation increases with the potential difference and can be interpreted as single collision dissociation on air molecules at centre-of-mass energies of several eV. Combination of fragmentation patterns at different CID enables distinction of isomers in the mixture on the basis of pseudoinversion.In-tube CID represents a simple and low-cost extension to SIFDT-MS that allows real-time identification of isomeric products of ion-molecule reactions on the basis of their structural differences and corresponding changes in fragmentation patterns with CID energy without significantly changing the net reaction time important for absolute quantification. Copyright © 2016 John WileySons, Ltd.

Reliable theoretical models of the chemical kinetics of the ionosphere of Saturn's moon, Titan, is highly dependent on the precision of the rates of the reactions of ambient ions with hydrocarbon molecules at relevant temperatures. A Variable Temperature Selected Ions Flow Tube technique, which has been developed primarily to study these reactions at temperatures within the range of 200-330 K, is briefly described. The flow tube temperature regulation system and the thermalisation of ions are also discussed. Preliminary studies of two reactions have been carried out to check the reliability and efficacy of kinetics measurements: (i) Rate constants of the reaction of CH3 (+) ions with molecular oxygen were measured at different temperatures, which indicate values in agreement with previous ion cyclotron resonance measurements ostensibly made at 300 K. (ii) Formation of CH3 (+) ions in the reaction of N2 (+) ions with CH4 molecules were studied at temperatures within the range 240-310 K which showed a small but statistically significant decrease of the ratio of product CH3 (+) ions to reactant N2 (+) ions with reaction temperature.

A selected ion flow tube, SIFT, study has been carried out of the reactions of H 3 O + , NO + and O 2 +• with seven structural isomers of hexanol with the common molecular formula C 6 H 14 O and molecular weight 102 that are commonly met in food science studies. The main objective is to provide the kinetic data, i.e., the rate constants and the product ion branching ratios to be included in the SIFT-MS kinetics database that would allow the separate identification and quantification of these compounds. The specific compounds involved are the primary alcohols 1-hexanol, CH 3 (CH 2 ) 5 OH; 2-ethyl-1-butanol, (C 2 H 5 ) 2 CHCH 2 OH; 4-methyl-1-pentanol, (CH 3 ) 2 CH(CH 2 ) 3 OH; secondary alcohols 2-hexanol, CH 3 (CH 2 ) 3 CH(OH)CH 3 ; 4-methyl-2-pentanol, (CH 3 ) 2 CHCH 2 CH(OH)CH 3 ; 3-hexanol, CH 3 (CH 2 ) 2 CH(OH)CH 2 CH 3 and a tertiary alcohol 3-methyl-3-pentanol, (CH 3 CH 2 ) 2 C(CH 3 )OH. The reactions of H 3 O + proceed via dissociative proton transfer invariably producing C 6 H 13 + hydrocarbon ions ( m / z 85). The reactions of NO + proceed predominantly via hydride ion transfer producing C 6 H 13 O + ions ( m / z 101) for the primary and secondary hexanols, with a minor fragmentation channel for the primary hexanols, when a H 2 O molecule is lost from the major product ion resulting in C 6 H 11 + ions ( m / z 83), and a minor channel representing the process of hydroxide ion transfer producing C 6 H 13 + ions ( m / z 85) for secondary alcohols. The latter reaction is also the dominant process for the tertiary alcohol. O 2 +• reacts by dissociative charge transfer in all reactions resulting in multiple product ions analogous to electron ionization. The differences in product ion branching ratios and fragmentation patterns can thus assist SIFT-MS identification of the different hexanol isomers in cases when they are not present in complex mixtures.

To summarize the recent progress made in noninvasive monitoring of volatile compounds in exhaled breath and above biological liquids, as they are becoming increasingly important in assessing the nutritional and clinical status and beginning to provide support to conventional clinical diagnostics and therapy. To indicate the potential of these developments in medicine and the specific areas which are currently under investigation.The significance of the following breath gases and their concentrations are reported: acetone and the influence of diet; ammonia confirmed as an indicator of dialysis efficacy; hydrogen and the (13)CO(2)/(12)CO(2) ratio (following the ingestion of (13)C-labeled compounds) as related to gastric emptying and bowel transit times; hydrogen cyanide released by Pseudomonas and its detection in breath of children with cystic fibrosis; and multiple trace compounds in breath of patients with specific pathophysiological conditions and 'metabolic profiling'.Advanced analytical methods, especially exploiting mass spectrometry, are moving breath analysis towards the clinical setting; some trace gas metabolites are already being exploited in diagnosis and therapy. Much effort is being given to the search for biomarkers of tumours in the body. HCN as an indicator of the presence of Pseudomonas in the airways has real potential in therapeutically alleviating the symptoms of cystic fibrosis.

Infection by Pseudomonas aeruginosa (PA) is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Breath analysis could potentially be a useful diagnostic of such infection, and analyses of volatile organic compounds (VOCs) emitted from PA cultures are an important part of the search for volatile breath markers of PA lung infection. Our pilot experiments using solid-phase microextraction, SPME and gas chromatography/mass spectrometric (GC/MS) analyses of volatile compounds produced by PA strains indicated a clear presence of methyl thiocyanate. This provided a motivation to develop a method for real-time online quantification of this compound by selected ion flow tube mass spectrometry, SIFT-MS. The kinetics of reactions of H3O+, NO+ and O2+• with methyl thiocyanate at 300 K were characterized and the characteristic product ions determined (proton transfer for H3O+, rate constant 4.6 × 10–9 cm3 s–1; association for NO+, 1.7 × 10–9 cm3 s–1 and nondissociative charge transfer for O2+•, 4.3 × 10–9 cm3 s–1). The kinetics library was extended by a new entry for methyl thiocyanate accounting for overlaps with isotopologues of hydrated hydronium ions. Solubility of methyl thiocyanate in water (Henry's law constant) was determined using standard reference solutions and the linearity and limits of detection of both SIFT-MS and SPME-GC/MS methods were characterized. Thirty-six strains of PA with distinct genotype were cultivated under identical conditions and 28 of them (all also producing HCN) were found to release methyl thiocyanate in headspace concentrations greater than 6 parts per billion by volume (ppbv). SIFT-MS was also used to analyze the breath of 28 children with CF and the concentrations of methyl thiocyanate were found to be in the range 2–21 ppbv (median 7 ppbv). Copyright © 2011 John Wiley & Sons, Ltd.

The purpose of this short review is to describe the origins and the principles of operation of selected-ion flow-tube mass spectrometry (SIFT-MS) and proton-transfer-reaction mass spectrometry (PTR-MS), and their application to the analysis of biogenic volatile organic compounds (BVOCs) in ambient air, the humid air (headspace) above biological samples, and other samples. We briefly review the ion chemistry that underpins these analytical methods, which allows accurate analyses. We pay attention to the inherently uncomplicated sampling methodologies that allow on-line, real-time analyses, obviating sample collection into bags or onto traps, which can compromise samples. Whilst these techniques have been applied successfully to the analysis of a wide variety of media, we give just a few examples of data, including for the analysis of BVOCs that are present in tropospheric air and those emitted by plants, in exhaled breath and in the headspace above cell and bacterial cultures (which assist clinical diagnosis and therapeutic monitoring), and the products of combustion. The very wide dynamic ranges of real-time analyses of BVOCs in air achieved by SIFT-MS and PTR-MS – from sub-ppbv to tens of ppmv – ensure that these analytical methods will be applied to many other media, especially when combined with gas-chromatography methods, as recently trialed.

Preliminary measurements have been made of the volatile compounds emitted by the bacterium E. coli JM109 cultured in the commonly used media Dulbecco's modified Eagle's medium (DMEM) and lysogeny broth (LB) using selected ion flow tube mass spectrometry, SIFT-MS, as a step towards the real time, non-invasive monitoring of accidental infections of mammalian cell cultures. In one procedure, the culture medium alone and the E. coli cells/medium combination were held at 37 °C in bottles sealed with septa for a given time period, usually overnight, to allow the bacterium to proliferate, after which the captured headspace was analysed directly by SIFT-MS. Several compounds were seen to be produced by the E. coli cells that depended on the liquid medium used: when cultured in DMEM, copious amounts of ethanol, acetaldehyde and hydrogen sulphide were produced; in LB ammonia is the major volatile product. In a second procedure, to ensure aerobic conditions prevailed in the cell culture, selected volatile compounds were monitored by SIFT-MS in real time for several hours above the open-to-air E. coli/DMEM culture held at close to 37 °C. The temporal variations in the concentrations of some compounds, which reflect their production rates in the culture, indicate maxima. Thus, the maxima in the ethanol and acetaldehyde production are a reflection of the reduction of glucose from the DMEM by the vigorous E. coli cells and the maximum in the hydrogen sulphide level is an indication of the loss of the sulphur-bearing amino acids from the DMEM. Serendipitously, emissions from DMEM inadvertently infected with the bacterium C. testosteroni were observed when large quantities of ammonia were seen to be produced. The results of this preliminary study suggest that monitoring volatile compounds might assist in the early detection of bacterial infection in large-scale bioreactors.

A study of the reactions of H 3 O + , NO + and O 2 + ions with two groups of four isobaric, biologically active compounds with molecular weights, MW, of 86u and 88u has been carried out using the selected ion flow tube, SIFT, technique in preparation for the analyses of these compounds in the headspace of bacterial and cell cultures using SIFT-MS. These compounds are: MW 86u: 2,3 butanedione (diacetyl), C 4 H 6 O 2 ; allyl ethyl ether, C 5 H 10 O, cyclopropane carboxylic acid, C 4 H 6 O 2 : γ-butyrolactone, C 4 H 6 O 2 . MW 88u: 3-hydroxybutanone (acetoin), C 4 H 8 O 2 ; n-butyric acid, C 4 H 8 O 2 ; ethyl acetate, C 4 H 8 O 2 ; pyruvic acid, C 3 H 4 O 3 . All 24 reactions proceed at the gas kinetic rate, the dominant primary product ions of the H 3 O + reactions being the protonated reactant molecules, MH + with a common mass-to-charge ratio, m / z , in each group of isobaric compounds; those of the NO + reactions being the adduct ions, NO + M, also with a common m / z value; for the O 2 + ion reactions, fragmentation ions of the nascent parent ion M + are produced. SIFT-MS analysis of each compound individually is straightforward, but when more than one isobaric compound is present, SIFT-MS analyses become more challenging. However, hydration of some, but not all, of the primary MH + and NO + M primary ions occurs, variously generating MH + (H 2 O) 1,2 and NO + MH 2 O ions, and the occurrence/non-occurrence of these hydrates can assist in distinguishing between some of the isobaric compounds. From the kinetic data obtained in this study, the required SIFT-MS kinetics library entries for each compound can be constructed that allow their quantification. As an example, SIFT-MS spectra are presented relating to the analysis of the headspace of incubated yoghurt, which show the presence of several volatile organic compounds, including acetoin and diacetyl.

Reactions of (14)N(+)((3)P), (15)N(+)((3)P), and Kr(+) with propane, propene, and propyne were studied using the selected ion flow tube, SIFT, technique. Thermal rate constants in all N(+)/C(3) systems were k = (2 ± 0.4) × 10(-9) cm(3) molecule(-1) s(-1), close to the collisional rate constants. With propane and propene, only hydrocarbon ions were found among the products of reactions with N(+); in propyne about 15% of the products were N-containing ions (C(3)H(2)N(+), C(2)H(4)N(+), C(2)H(3)N(+), C(2)H(2)N(+)), and the rest were hydrocarbon ions. A comparison with product ions from electron transfer between Kr(+) (of recombination energy similar to that for N(+)((3)P)) and the C(3) hydrocarbons and further analysis of the results led to an estimation of an approximate ratio of electron transfer vs hydride-ion transfer reactions leading to the hydrocarbon product ions: in propane the ratio was 2:1, in propene 3:1, and in propyne 5:1. A fraction of product ions resulted from reactions leading to the excited neutral product N*.

Time-resolved Fourier transform (FT) spectrometry was used to study the dynamics of radical reactions forming the HCN and HNC isomers in pulsed glow discharges through vapors of BrCN, acetonitrile (CH(3)CN), and formamide (HCONH(2)). Stable gaseous products of discharge chemistry were analyzed by selected ion flow tube mass spectrometry (SIFT-MS). Ratios of concentrations of the HNC/HCN isomers obtained using known transition dipole moments of rovibrational cold bands v(1) were found to be in the range 2.2-3%. A kinetic model was used to assess the roles the radical chemistry and ion chemistry play in the formation of these two isomers. Exclusion of the radical reactions from the model resulted in a value of the HNC/HCN ratio 2 orders of magnitude lower than the experimental results, thus confirming their dominant role. The major process responsible for the formation of the HNC isomer is the reaction of the HCN isomer with the H atoms. The rate constant determined using the kinetic model from the present data for this reaction is 1.13 (±0.2) × 10(-13) cm(3) s(-1).

The selected ion flow tube (SIFT) was used to study the reactions of the three SIFT-MS precursor ions H3O+, NO+ and O2+ with six phytogenic esters: hexyl acetate, phenethyl acetate, benzyl acetate, methyl salicylate, methyl benzoate and benzyl benzoate. These compounds are emitted into the atmosphere by various species of plants and play a role in communication between individual plants and also amongst different species. Thus, it is necessary to know the rate constants and branching ratios of the different ion products of these reactions for identification and quantification by SIFT-MS. The results of this study show that the reactions of H3O+ with the esters proceed via proton transfer, which is non-dissociative for methyl salicylate, entirely dissociative for benzyl benzoate and partly dissociative for the remaining four esters. All protonated esters readily associate with water molecules with the notable exception of methyl salicylate. All six NO+ reactions result in formation of adduct ions in parallel with charge transfer or with reactions leading to fragment ions. All six O2+ reactions proceed by charge transfer with the production of one or two major fragment ions; the parent molecular radical cation is formed in three reactions only. Kinetic library entries allowing unambiguous quantification of the six esters by SIFT-MS are presented together with their experimental validation.

In response to a need for the measurement of the deuterium (D) abundance in water and aqueous liquids exceeding those previously recommended when using flowing afterglow mass spectrometry (FA-MS) and selected ion flow tube mass spectrometry (SIFT-MS) (i.e. 1000 parts per million, ppm), we have developed the theory of equilibrium isotopic composition of the product ions on which these analytical methods are based to encompass much higher abundances of D in water up to 10,000 ppm (equivalent to 1%). This has involved an understanding of the number density distributions of the H, D, 16O, 17O and 18O isotopes in the isotopologues of H3O+(H2O)3 hydrated ions (i.e. H9O 4 + cluster ions) at mass-to-charge ratios (m/z) of 73, 74 and 75, the relative ion number densities of which represent the basis of FA-MS and SIFT-MS analyses of D abundance. Specifically, an extended theory has been developed that accounts for the inclusion of D atoms in the m/z 75 ions, which increasingly occurs as D abundance in the water is increased, and which is used as a reference signal for the m/z 74 ions in the measurement of D abundance. In order to investigate the efficacy of this theory, experimental measurements of deuterium abundance in standard mixtures were made by the SIFT-MS technique using two similar instruments and the results compared with the theory. It is demonstrated that the parameterization of experimental data can be used to formulate a simple calculation algorithm for real-time SIFT-MS measurements of D abundance to an accuracy of 1% below 1000 ppm and degrades to about 2% at 10,000 ppm.

The development of selected ion flow tube mass spectrometry, SIFT-MS, is described from its inception as the modified very large SIFT instruments used to demonstrate the feasibility of SIFT-MS as an analytical technique, towards the smaller but bulky transportable instruments and finally to the current smallest Profile 3 instruments that have been located in various places, including hospitals and schools to obtain on-line breath analyses. The essential physics and engineering principles are discussed, which must be appreciated to design and construct a SIFT-MS instrument. The versatility and sensitivity of the Profile 3 instrument is illustrated by typical mass spectra obtained using the three precursor ions H(3)O(+), NO(+) and O(2)(+)·, and the need to account for differential ionic diffusion and mass discrimination in the analytical algorithms is emphasized to obtain accurate trace gas analyses. The performance of the Profile 3 instrument is illustrated by the results of several pilot studies, including (i) on-line real time quantification of several breath metabolites for cohorts of healthy adults and children, which have provided representative concentration/population distributions, and the comparative analyses of breath exhaled via the mouth and nose that identify systemic and orally-generated compounds, (ii) the enhancement of breath metabolites by drug ingestion, (iii) the identification of HCN as a marker of Pseudomonas colonization of the airways and (iv) emission of volatile compounds from urine, especially ketone bodies, and from skin. Some very recent developments are discussed, including the quantification of carbon dioxide in breath and the combination of SIFT-MS with GC and ATD, and their significance. Finally, prospects for future SIFT-MS developments are alluded to.

A study has been carried out of the decay of ethanol in mouth-exhaled and nose-exhaled breath of two healthy volunteers following the ingestion of various doses of alcohol at different dilutions in water. Concurrent analyses of sequential single breath exhalations from the two volunteers were carried out using selected ion flow tube mass spectrometry, SIFT-MS, on-line and in real time continuously over some 200 min following each alcohol dose by simply switching sampling between the two volunteers. Thus, the time interval between breath exhalations was only a few minutes, and this results in well-defined decay curves. Inspection of the mouth-exhaled and nose-exhaled breath data shows that mouth contamination of ethanol diminished to insignificant levels after a few minutes. The detailed results of the analyses of nose-exhaled breath show that the peak levels and the decay rates of breath ethanol are dependent on the ethanol dose and the volume of ethanol/water mixture ingested. From these data, both the efficiency of the first-pass metabolism of ethanol and the indications of gastric emptying rates at the various doses and ingested volumes have been obtained for the two volunteers. Additionally and simultaneously, acetaldehyde, acetic acid and acetone were measured in each single breath exhalation. Acetaldehyde, the primary product of ethanol metabolism, is seen to track the breath ethanol. Acetic acid, a possible secondary product of this metabolism, was detected in the exhaled breath, but was shown to largely originate in the oral cavity. Breath acetone was seen to increase over the long period of measurement due to the depletion of nutrients.

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to investigate if absolute levels of trace compounds in the headspace of ethanol/water vapour mixture can be quantified. This case study was directed towards the analysis of methylamine in distilled ethanol of agricultural origin because of its relevance to quality control legislation in the distillery industry. This has required a detailed study of the ion chemistry occurring – initiated by H3O+ precursor ions – when ethanol/water vapour mixtures are introduced into the H3O+/helium carrier gas swarm and has resulted in the construction of a full scheme of the complex ionic reactions that occur. It has been found that under the SIFT-MS flow reactor conditions (He pressure 130 Pa and temperature 299 K) the terminating ions of the several parallel and sequential reactions that occur are the proton bound ethanol clusters ions, C2H5OH2+(C2H5OH)n, with n = 1,2,3, proton bound trimer (n = 2) being the dominant species. These ethanol cluster ions can be used as precursor (reagent) ions for the chemical ionisation of the methylamine present in the ethanol/water vapour, which produces two characteristic product ions CH3NH2H+(C2H5OH)1,2 that are used for the methylamine analysis. The ratio of the product ion count rate to the precursor ion count rate is used in an analogous way to the routinely used for SIFT-MS analyses to quantify the methylamine concentration. The results of calibration experiments show that using SIFT-MS it is possible to quantify methylamine in liquid ethanol/water mixtures at levels of 0.1 mg/L or greater.

Numerous analyses of exhaled breath using selected ion flow tube mass spectrometry, SIFT-MS, over the last few years have revealed the presence of volatile compounds with molecular weight 60 and the concern has been to identify which of the isobaric compounds from the set of 1-propanol, 2-propanol, acetic acid and methyl formate are present in human breath. The problem is compounded by the formation of hydrates of the characteristic primary product ions of the reactions of the H 3 O + and NO + precursor ions with these compounds, this being particularly efficient for humid samples such as exhaled breath. Thus, the resulting product ion spectra are complex and choices have to be made as to which of the characteristic product ions and their hydrates can best be used for the quantitative analyses. To facilitate this choice for the particular problem of identifying and quantifying the four aforementioned isobaric compounds, a study has been made of the ion chemistry of H 3 O + and NO + with the two propanol isomers, acetic acid and methyl formate for increasing sample humidity up to that of exhaled breath, which is about 6% by volume. The problems involved in the separate analysis of propanol have been met and solved by previous SIFT-MS studies and now the present study has revealed how acetic acid and methyl formate can be separately identified in a humid mixture using NO + precursor ions only. Following this work, the kinetics database entries for the SIFT-MS analyses of these compounds in breath have been constructed and the analysis of the exhaled breath of five healthy volunteers showed that, in addition to the propanol isomers, acetic acid was present at levels typically within the range from 30 to 60 parts-per-billion by volume and that methyl formate was not present above the limit of detection.

The reactions of carbon dioxide, CO(2), with the precursor ions used for selected ion flow tube mass spectrometry, SIFT-MS, analyses, viz. H(3)O(+), NO(+) and O(2) (+), are so slow that the presence of CO(2) in exhaled breath has, until recently, not had to be accounted for in SIFT-MS analyses of breath. This has, however, to be accounted for in the analysis of acetaldehyde in breath, because an overlap occurs of the monohydrate of protonated acetaldehyde and the weakly bound adduct ion, H(3)O(+)CO(2), formed by the slow association reaction of the precursor ion H(3)O(+) with CO(2) molecules. The understanding of the kinetics of formation and the loss rates of the relevant ions gained from experimentation using the new generation of more sensitive SIFT-MS instruments now allows accurate quantification of CO(2) in breath using the level of the H(3)O(+)CO(2) adduct ion. However, this is complicated by the rapid reaction of H(3)O(+)CO(2) with water vapour molecules, H(2)O, that are in abundance in exhaled breath. Thus, a study has been carried out of the formation of this adduct ion by the slow three-body association reaction of H(3)O(+) with CO(2) and its rapid loss in the two-body reaction with H(2)O molecules. It is seen that the signal level of the H(3)O(+)CO(2) adduct ion is sensitively dependent on the humidity (H(2)O concentration) of the sample to be analysed and a functional form of this dependence has been obtained. This has resulted in an appropriate extension of the SIFT-MS software and kinetics library that allows accurate measurement of CO(2) levels in air samples, ranging from very low percentage levels (0.03% typical of tropospheric air) to the 6% level that is about the upper limit in exhaled breath. Thus, the level of CO(2) can be traced through single time exhalation cycles along with that of water vapour, also close to the 6% level, and of trace gas metabolites that are present at only a few parts-per-billion. This has added a further dimension to the analysis of major and trace compounds in breath using SIFT-MS.

Urine is commonly analysed in clinical practice by a variety of liquid-phase techniques to check for excessive ketone bodies, proteins and salts to name just a few compounds. However, little work has been carried out to measure the volatile compounds emitted by urine since these do not yet have an established role in clinical diagnosis. There is, however, a growing body of evidence that these volatile compounds can be indicators of adverse physiological conditions and disease and with the advent of sensitive gas-phase analytical methods they can be quickly quantified in urine headspace and potentially provide valuable support for clinical diagnosis. Thus, we are developing selected ion flow tube mass spectrometry, SIFT-MS, for the real-time analysis of urine headspace, ultimately to support rapid diagnosis in the clinical environment. In this paper we focus on volatile ketones in the headspace of aqueous solutions and urine donated by three healthy volunteers. Using SIFT-MS, we have unambiguously quantified in urine headspace acetone, by far the most abundant ketone, butanone, pentanone, hexanone and heptanone using NO(+) precursor ions. Further to this, we have determined the Henry's Law coefficients, HLC, for these ketones in aqueous solution to allow the liquid-phase concentrations in urine to be estimated from headspace levels of their vapours. In addition, the influence of the addition of physiological amounts of dissolved urea, sodium chloride and hydrochloric acid on the partitioning of these ketones between the aqueous phase and gas phase has been investigated and found to be small, which gives greater credence to the use of the HLC obtained using aqueous solutions for the estimation of ketone concentrations in urine. Finally, parallel measurements of the levels of acetone in exhaled breath and urine headspace have been obtained and shown to be very similar, which gives support to the previous deduction from breath analysis that acetone is a truly systemic compound.

The major thrust of this paper is to describe how the current selected ion flow tube mass spectrometry (SIFT-MS) Profile 3 instruments can be configured to provide reliable quantification of the trace gases present in air and exhaled breath by accounting for the phenomena of differential diffusion of the analytical precursor and product ions in the flow tube reactor and mass discrimination in the ion sampling/analytical quadrupole mass spectrometer/detection system. If not accounted for these phenomena, especially the latter, can result in serious errors in quantification. Hence, it is described how H3O+ precursor ions are totally converted to a range of product ions within the mass-to-charge ratio, m/z, range from 18 to 201 and, thus, how the ion currents collected by the downstream ion sampling orifice disc and the count rates of these ions as determined by the analytical detection system at the various m/z are used to provide values of both the diffusion enhancement coefficient, De, and the mass discrimination factor, Mr, that are required to allow accurate trace gas analyses. It is indicated how all such SIFT-MS instruments can be properly configured using a similar but abbreviated procedure. Finally, it is shown how the properly configured Profile 3 instrument provides consistent and reliable analyses of acetone using H3O+, NO+ and O2+, 2-pentanone and 2-hexanone using H3O+ and NO+, and ammonia using H3O+ and O2+ precursor ions in (relatively dry) air samples and in (humid) single breath exhalations.

This paper describes how weakly bound adduct ions form when the precursor ions used in selected ion flow mass spectrometry, SIFT-MS, analyses, viz. H 3 O + , NO + and O 2 + , associate with the major components of air and exhaled breath, N 2 , O 2 and CO 2 . These adduct ions, which include H 3 O + N 2 , H 3 O + CO 2 , NO + CO 2 , O 2 + O 2 and O 2 + CO 2 , are clearly seen when dry air containing 5% CO 2 (typical of that in exhaled breath) is analysed using SIFT-MS. These adduct ions must not be misinterpreted as characteristic product ions of trace gases; if so, serious analytical errors can result. However, when exhaled breath is analysed these adduct ions are partly removed by ligand switching reactions with the abundant water molecules and the problems they represent are alleviated. But the small fractions of the adduct ions that remain in the SIFT-MS spectra, and especially when they are isobaric with genuine characteristic product ion of breath trace gases, can result in erroneous quantifications; such is the case for H 3 O + N 2 interfering with breath ethanol analysis and H 3 O + CO 2 with breath acetaldehyde analysis. However, these difficulties can be overcome when the isobaric adduct ions are properly recognised and excluded from the analyses; then these two important compounds can be properly quantified in breath. The presence of O 2 + CO 2 in the product ion spectra interferes with the analysis of CS 2 present at low levels in exhaled breath. It is likely that similar problems will occur as other trace compounds are detected in exhaled breath when consideration will have to be given to the possibility of overlapping between their characteristic product ions and ions produced by hitherto unknown reactions. Similar problems are evident in other systems; for example, H 3 O + CH 4 adduct ions are observed in both SIFT-MS analyses of methane rich mixtures like biologically generated waste gases and in model planetary atmospheres.

Aims To use selected ion flow tube mass spectrometry (SIFT-MS) to analyse the molecular species emitted by heated ‘street’ cannabis plant material, especially targeting ammonia. Materials and methods Samples of ‘street’ cannabis leaf, held under a UK Home Office licence, were prepared by finely chopping and mixing the material. The samples were then heated in commercially available devices. The air containing the released gaseous compounds was sampled into the SIFT-MS instrument for analysis. Smoke from standard 3% National Institute on Drug Abuse (NIDA) cannabis cigarettes was also analysed. Findings For ‘street’ cannabis, ammonia was present in the air samples from the devices at levels approaching 200 parts per million (p.p.m.). This is compared with peak levels of 10 p.p.m. using NIDA samples of known provenance and tetrahydrocannabinol content (3%). Several other compounds were present at lower levels, including acetaldehyde, methanol, acetone, acetic acid and uncharacterized terpenes. Conclusions Awareness of the risks of inhaling the smoke directly from burning cannabis has led to the development of a number of alternative methods of delivery, which are claimed to be safer than direct smoking. Ammonia at toxic levels is produced from heating ‘street’ cannabis in these commercially available devices. Thus, the use of these devices to deliver ‘street’ cannabis is now open to question and further research is needed to investigate their safety.

International audience; The industrial production of poly (ethylene terephthalate), PET, continues to increase and thus it is important to understand the composition of fumes resulting from its disposal as a part of incinerated waste. In this study samples of PET material were combusted in a furnace corresponding to the German standard DIN 53 436 at the temperatures of 500○C, 800○C (in an air flow) and also uncontrolled burning in air. The gaseous products were then analysed using three different analytical methods: high resolution Fourier transform infrared spectroscopy (FTIR), selected ion flow tube mass spectrometry (SIFT-MS) and gas chromatography mass spectrometry (GC-MS). Carbon dioxide, methane, ethylene, acetylene, formaldehyde (methanal) and acetaldehyde (ethanal) were detected by FTIR. Water, methane, acetaldehyde, ethylene, formaldehyde, methanol, acetone, benzene, terephthalic acid, styrene (ethenylbenzene), ethanol, toluene (methylbenzene), xylene (dimethylbenzene), ethylbenzene, naphthalene, biphenyl and phenol concentrations were all quantified by both SIFT-MS and GC-MS. Additionally, the fumes resulting from uncontrolled combustion in air were analysed by FTIR which resolves the rotation-vibration structure of the absorption bands of formaldehyde (2779.90 and 2778.48 cm-1) and propane, which was identified from characteristic vibrations of CH3 groups at 2977.00 and 2962.00 cm-1. The spectra were compared to the reference standards.

A study has been carried out of the reactions of three isomers of hydroxybutyric acid, giving special attention to 3-hydroxybutyric acid, 3-HBA, with H 3 O + and NO + ions to acquire the required kinetic data for a selected ion flow tube mass spectrometry, SIFT-MS, search for 3-HBA in the headspace of urine since it is known to be one of the “ketone bodies” important in the diagnosis of ketoacidosis. Thus, the product ions formed in the reactions of the H 3 O + and NO + precursor ions with the three hydroxy acids were established by sampling the headspace above the pure compounds over a range of absolute humidities from 1.5% (ambient air) to 6% (liquid headspace at 37 C and exhaled breath). Then these data, together with the rate coefficients for the reactions estimated by calculation, were used to detect and quantify 3-HBA in the headspace of an aqueous solution of this compound of known concentration and above urine donated by two volunteers. The level of 3-HBA above the urine samples after they were acidified with hydrochloric acid was seen to be typically 40 parts-per-billion, ppb, which is much lower than that for acetone seen to be typically 800 ppb. Exploiting the aqueous solution data as a reference, the 3-HBA concentration in the urine samples was estimated to be about 1–2 mmol/L, which is typical of the urine from healthy individuals.