Abstract: We report a fast, sensitive, real-time method to measure monobromamine, monochloramine and dichloramine using selected ion flow tube mass spectrometry (SIFT-MS). Relative rate coefficients and product distributions are reported for the reagent ions H3O+ and O2 +. Rapid reactions with the haloamines were observed with H3O+ and O2 + but no fast reaction was found with NO+. A slow reaction between NO+ and dichloramine was observed. We demonstrate the feasibility of determining these compounds in a single human breath for which the limit of detection is approaching 10 parts per billion (ppb). We also report preliminary measurements of these compounds in the breath of individuals where the concentrations of bromamine and chloramine ranged from 10 to 150 ppb.

Abstract: ABSTRACT: BACKGROUND: Selected ion flow tube mass spectrometry (SIFT-MS) allows the real time quantification of trace gases in air. Due to its tolerance of high humidity levels the technique is particularly suited to the chemical analysis of breath. The detection limit of SIFT-MS has previously reported to be approximately 5 - 10 PPBV which is insufficient for the measurement of some low abundance constituents of breath. Recent developments in the design of SIFT-MS instruments have increased the ion precursor count rates. It is, however, unclear as to how these advances will affect instrument sensitivity for breath analysis. FINDINGS: Standard gases were prepared by adding known quantities of compounds present at zero or very low levels in breath (xylene and toluene) to either humidified bottled air or actual human breath. These were then analysed by SIFT-MS to calculate the limits of detection for each compound under conditions which mimic a single breath exhalation. For xylene and toluene the limits of detection was approximately 0.5 PPBV per 10 seconds of analysis time. Results gained using this level of sensitivity suggested the presence of low levels of the compounds indole and methylindole in human alveolar and static oral air, although further studies are necessary to confirm these findings. CONCLUSION: Recent advances in SIFT-MS have increased the techniques sensitivity for breath analysis into the sub PPBV range enabling the real time quantification of low level trace gases in human breath.

Abstract: Collection of exhaled breath condensate (EBC) is a relatively simple noninvasive method of breath analysis; however, no data have been reported that would relate concentration of volatile compounds in EBC to their gaseous concentrations in exhaled air. The aim of the study was to investigate which volatile compounds are present in EBC and how their concentrations relate to results of direct breath analysis. Thus, samples of EBC were collected in a standard way from several subjects and absolute levels of several common volatile breath metabolites (ammonia, acetone, ethanol, methanol, propanol, isoprene, hydrogen cyanide, formaldehyde and acetaldehyde) were then determined in their headspace using selected ion flow tube mass spectrometry (SIFT-MS). Results are compared with those from on-line breath analyses carried out immediately before collecting the EBC samples. It has been demonstrated that SIFT-MS can be used to quantify the concentrations of volatiles in EBC samples and that, for methanol, ammonia, ethanol and acetone, the EBC concentrations correlate with the direct breath levels. However, the EBC concentrations of isoprene, formaldehyde, acetaldehyde, hydrogen cyanide and propanol do not correlate with direct breath measurements.

Abstract: 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.

Abstract: A study has been carried out, involving three healthy volunteers, of the ammonia levels in breath exhaled via the mouth and via the nose and in the static oral cavity using on-line, selected ion flow tube mass spectrometry (SIFT-MS), obviating the problems associated with sample collection of ammonia. The unequivocal conclusion drawn is that the ammonia appearing in the mouth-exhaled breath of the three volunteers is largely generated in the oral cavity and that the ammonia originating at the alveolar interface in the lungs is typically at levels less than about 100 parts-per-billion, which is a small fraction of the total breath ammonia. This leads to the recommendation that exhaled breath analyses should focus on nose-exhaled breath if the objective is to use breath analysis to investigate systemic, metabolic disease.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) has been used to carry out a pilot parallel study on five volunteers to determine changes occurring in several trace compounds present in exhaled breath and emitted from skin into a collection bag surrounding part of the arm, before and after ingesting 75 g of glucose in the fasting state. SIFT-MS enabled real-time quantification of ammonia, methanol, ethanol, propanol, formaldehyde, acetaldehyde, isoprene and acetone. Following glucose ingestion, blood glucose and trace compound levels were measured every 30 min for 2 h. All the above compounds, except formaldehyde, were detected at the expected levels in exhaled breath of all volunteers; all the above compounds, except isoprene, were detected in the collection bag. Ammonia, methanol and ethanol were present at lower levels in the bag than in the breath. The aldehydes were present at higher levels in the bag than in breath. The blood glucose increased to a peak about 1 h post-ingestion, but this change was not obviously correlated with temporal changes in any of the compounds in breath or emitted by skin, except for acetone. The decrease in breath acetone was closely mirrored by skin-emitted acetone in three volunteers. Breath and skin acetone also clearly change with blood glucose and further work may ultimately enable inferences to be drawn of the blood glucose concentration from skin or breath measurements in type 1 diabetes.

Abstract: BACKGROUND: Despite its importance, total body water (TBW) is usually estimated rather than measured due to the complexity of isotope dilution methods. The aim of this study was to demonstrate the applicability in haemodialysis (HD) patients of a recently developed on-line breath test, previously validated in healthy subjects, that uses the gold standard deuterium dilution method to measure TBW. In particular we wished to show that a pre-dialysis estimation was as good as a post-dialysis equilibrated measurement in order to avoid patients needing to remain behind after dialysis treatment. METHODS: The dispersal kinetics of breath HDO, measured using a flowing afterglow mass spectrometer (FA-MS) following ingestion of D(2)O immediately post-dialysis, were determined in 12 haemodialysis patients and used to calculate the absolute TBW(PostHD) after full equilibration. TBW(PreHD) was then determined from breath samples taken immediately prior to the next dialysis. This measurement was adjusted for the interdialytic weight change and urine output (TBW(PreHD-adjusted)) and compared to the TBW(PostHD). The accuracy and precision of FA-MS was also assessed using known concentrations of deuterium-enriched water samples. RESULTS: Mean TBW(PostHD) was 50.0 +/- 9.3 L and TBW(PreHD-adjusted) was 50.7 +/- 9.0 L. They were highly correlated (R = 0.99, P < 0.001) with a CV of 2.6%. The mean difference was +0.74 L (SEM 0.35, 95% CI -0.03 to 1.51 L, P = 0.059), compatible with a daily insensible loss of 0.37 L. Accuracy and precision of FA-MS were comparable to the previous validation work. CONCLUSIONS: This non-invasive adaptation of the D isotope dilution method for determining TBW can be applied to haemodialysis patients who show deuterium equilibration kinetics identical to normal subjects; a pre-dialysis estimation may be used to determine TBW, and so avoiding the necessity to remain behind after dialysis making this suitable for application in the clinical setting.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) has been employed to study the ion-molecule reactions of 17 alkyl esters reacting with the common SIFT-MS reagent ions, H3O+, H3O+.nH2O (n = 1, 2, 3), NO+, and O2+. The majority of reactions were observed to proceed at or near collision rate, with the exception of H3O+.3H2O, which was found to be slow for 8 of 17 alkyl esters. Unexpected product ions in the form of the parent carboxylic acid cation were observed to arise from the H3O+ and NO+ reactions of some alkyl esters. The observed reactions have been probed by the ab initio CBS-4M and G2(MP2,SVP) methods. The postulated reaction pathway involves a 1,5 H atom migration from a beta-carbon onto the carbonyl oxygen.

Abstract: Thermal desorption (TD) is commonly employed for volatile chemical analysis, it being the method of choice for occupational health and safety monitoring. TD allows for offline capture of volatiles onto a solid sorbent followed by desorption and analysis at a later time. Although TD is routinely used in conjunction with gas chromatography (TD-GC), the assay throughput is low and requires the use of gas standards for quantification. Another technique increasingly employed for volatile chemical analysis, selected ion flow tube mass spectrometry (SIFT-MS), is capable of real-time absolute (i.e. without calibration standards) quantification of volatile chemicals present at single digit parts per billion or higher concentrations. SIFT-MS is, however, normally used for online direct analysis of gas samples rather than offline collection and analysis. The goal of this study was to determine whether a combination of TD and SIFT-MS could be used to quantify volatile compounds, specifically xylene and toluene, more rapidly than TD-GC and without the need for calibration standards. SIFT-MS was able to quantify xylene and toluene levels within 45 s of desorption. Due to the robustness of the SIFT-MS analysis in the presence of water vapour and other major components of air, the purging of tubes usually required to remove these constituents during the TD cycle was not required, therefore reducing the TD cycle time. Comparing the quantity of xylene and toluene applied to the TD tube with the absolute levels quantified by SIFT-MS subsequent to desorption suggested a recovery of over 95% of the applied compound. We conclude that the combination of TD and SIFT-MS allows more rapid and accurate quantification of xylene and toluene (compared with TD-GC) to be achieved without the need for calibration standards, features which may be advantageous in applications requiring rapid analysis and high throughput.

Abstract: The emergence of primary and secondary oxidation products in New Zealand extra virgin olive oil during accelerated thermal oxidation was measured and correlated with the concentrations of 13 headspace volatile compounds measured by selected ion flow tube mass spectrometry (SIFT-MS). SIFT-MS is a mass spectrometric technique that permits qualitative and absolute quantitative measurements to be made from whole air, headspace, or breath samples in real-time down to several parts per billion (ppb). It is well-suited to high-throughput analysis of headspace samples. Propanal, hexanal, and acetone were found at high concentrations in a rancid standard oil, while propanal, acetone, and acetic acid showed marked increases with oxidation time for the oils used in this study. A partial least-squares (PLS) regression model was constructed, which allowed the prediction of peroxide values (PV) for three separate oxidized oils. Sensory rancidity was also measured, although the correlations of headspace volatile compounds with sensory rancidity score were less satisfactory, and too few results were available for the construction of a PLS regression model. A fast (approximately 1 min), reliable method for prediction of olive oil PVs by SIFT-MS was developed.

Abstract: The rate coefficients of the ion-molecule reactions between H3O+, NO+, O2+, and phosphine were determined using a selected ion flow tube. Using these data, the selected ion flow tube mass spectrometry (SIFT-MS) method was applied to the real-time measurement of phosphine in nitrogen without sample preparation down to concentrations in the mid parts per trillion range. This is the first reported measurement using SIFT-MS in the parts per trillion range. Linear dependencies on concentration were found from 190 ppt to the ppm range, and the limit of detection for a 10-s scan was 190 ppt (0.27 pg/mL).

Abstract: Exhaled breath analysis for clinical diagnosis and therapeutic monitoring is described with special reference to the techniques used and the underlying chemistry and physics involved. Brief outlines are given of the research carried out to date, and prospects for the future of this potentially valuable non-invasive technique are indicated.

Abstract: Selected ion flow tube mass spectrometry, (SIFT-MS), is a technique for simultaneous real-time quantification of several trace gases in air and exhaled breath. It relies on chemical ionization of the trace gas molecules in air/breath samples introduced into helium carrier gas, using H(3)O(+), NO(+) and O(2)(+) reagent (precursor ions). Reactions between the precursor ions and the trace gas molecules proceed for an accurately defined time, the precursor and product ions being detected and counted by a downstream mass spectrometer. Absolute concentrations of trace gases in single breath exhalation can be determined by SIFT-MS down to parts-per-billion (ppb) levels, obviating sample collection into bags or onto traps. Calibration using chemical standards is not required, as the concentrations are calculated using the known reaction rate constants and measured flow rates and pressures. SIFT-MS has been used for many pilot investigations in several areas of research, especially as a non-invasive breath analysis tool to investigate physiological processes in humans and animals, for clinical diagnosis and for therapeutic monitoring. Examples of the results obtained from several such studies are outlined to demonstrate the potential of SIFT-MS for trace gas analysis of air, exhaled breath and the headspace above liquids.

Abstract: The potential of breath analysis for clinical diagnosis and the strengths and weaknesses of the analytical methods used are discussed. Special attention is given to selected ion flow tube mass spectrometry, SIFT-MS, using which on-line real-time analyses of single breath exhalations can be carried out. Illustrative data on the concentration distributions of several breath metabolites amongst the healthy population are presented and their relations to disease when elevated above the normal are alluded to.

Abstract: A fast, efficient, real-time method for the quantitative analysis of the peroxide explosive, TATP, is described. The method utilizes rapid ion-molecule reactions of chemical reagent ions with the vapor above solid TATP. The reactions of three reagent ions (H3O+, O2+, NO+) were examined. Although all three ions exhibited a near-collision-rate reaction with TATP, only NO+ showed product ions that provide unequivocal evidence for a TATP-based explosive. The limit of detection of TATP in the gas phase is 10 ppb (4 x 10(-10) mol L(-1)).

Abstract: Samples (210 in total) of broncholaveolar lavages (BALs), obtained from patients hospitalized with pneumonia in various departments of two hospitals, were analysed using the method of solid phase microextraction-gas chromatography (SPME-GC) with FID detection. Up to 20% (9% unequivocally, 11% probably) of these samples was found to contain volatile fatty acids (VFAs) in the series from acetic acid to heptanoic acid. Importantly, the presence of these acids indicates the presence of fermenting anaerobic bacteria, which were not detected by the conventional microbiological examination. Other compounds, namely the heptanol and cyclohexanone, were also detected by this method in some samples. Cyclohexanone occurred almost exclusively in samples from patients receiving intensive care with mechanical ventilation, and is suspected to originate from plastic parts of ventilators. Selected representative samples were also analysed using further methods, namely gas chromatography-mass spectrometry (GC-MS) of native and silylated samples, and selected ion flow tube mass spectrometry (SIFT-MS). These methods confirmed the identities of above mentioned compounds, and detected numerous other compounds tentatively identified as various alcohols, aldehydes, ketones, esters and hydrogen cyanide, HCN. Most of these compounds occurred in small amounts and their origin and diagnostic significance remains uncertain, except, that is, for the HCN, which indicates the presence of Pseudomonas aeruginosa.

Abstract: Selected ion flow tube mass spectrometry, SIFT-MS, has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 males, 11 females) over a 6 month period. Volunteers provided breath samples each week between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ammonia, acetone and propanol. It was found that the concentration distributions of these compounds in breath were close to log-normal. The median ammonia level estimated as a geometric mean for all samples was 833 parts per billion (ppb) with a multiplicative standard deviation of 1.62, the values ranging from 248 to 2935 ppb. Breath ammonia clearly increased with increasing age in this volunteer cohort. The geometric mean acetone level for all samples was 477 parts per billion (ppb) with a multiplicative standard deviation of 1.58, the values ranging from 148 to 2744 ppb. The median propanol level for all samples was 18 ppb, the values ranging from 0 to 135 ppb. A weak but significant correlation between breath propanol and acetone levels is apparent in the data. The findings indicate the potential value of SIFT-MS as a non-invasive breath analysis technique for investigating volatile compounds in human health and in the diseased state.

Abstract: The value of the gas chromatography (GC) and selected ion flow tube mass spectrometry (SIFT-MS) combination for the analysis of trace gases is demonstrated by the quantification of acetone in air samples using the three precursor ions available to SIFT-MS, viz. H3O+, NO+ and O2+, and by the separation of the isomers 1-propanol and 2-propanol, and their analysis using H3O+ precursor ions. It is shown that the GC/SIFT-MS combination allows for accurate trace gas quantification obviating the regular, time-consuming calibrations that are usually required for the more commonly used detectors of GC systems, and the positive identification of isomers in mixtures that is often challenging using SIFT-MS alone. Thus, the GC/SIFT-MS combination paves the way to more confident analyses of complex mixtures such as exhaled breath.

Abstract: The ingestion of relatively large doses of the vitamin niacin by healthy volunteers results in a reddening of the skin, a skin 'flush'. Thus, we have carried out a study of the breath metabolites of two healthy volunteers following (i) the ingestion of 200 mg of immediate-release niacin, (ii) as (i) but preceded by the ingestion of 325 mg of aspirin that diminishes the skin 'flush', (iii) ingestion of 500 mg of slow-release niacin. On-line breath analysis was carried out using selected ion flow tube mass spectrometry, SIFT-MS. The interesting new observation is that the breath ammonia levels of both volunteers clearly increased following (i) and (ii), and an obvious skin flush did occur following (i) but not following (ii). The slow-release niacin (iii) did not result in a flush and the breath ammonia levels increased more slowly and did not reach the higher levels produced by (i) and (ii). The results of these experiments demonstrate that breath ammonia levels are dependent on the blood/plasma levels of niacin, but are not directly related to the flushing phenomenon, and that the observed increases in blood/breath ammonia levels are consistent with current knowledge of the metabolic pathways of niacin. The parallel measurements of breath isoprene are presented, which demonstrate the quality of breath analyses that can be achieved using SIFT-MS.

Abstract: Selected ion flow tube mass spectrometry, SIFT-MS, has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a six-month period. Volunteers provided breath samples each week between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on methanol in breath. The median methanol level determined using the H(3)O(+) precursor ions for all samples was 461 parts-per-billion (ppb), the concentrations for all the samples ranging from 32 to 1684 ppb. The distribution of breath methanol concentration is seen to be log-normal for this healthy population; the geometric mean was 450 ppb, close to the median value, and the multiplicative (geometric) standard deviation was 1.62. Breath methanol is not correlated with age, breath ethanol or ethanol consumed in the previous 24 h, but there was an inverse correlation with body mass index (BMI) for the cohort of volunteers recruited for this study. Observed breath methanol levels are well compatible with the previously published blood methanol levels. Some tentative suggestions are made concerning the origin of endogenous methanol.

Abstract: BACKGROUND: Selected ion flow tube mass spectrometry allows trace gas quantification in exhaled breath and in the air/vapor above liquids (headspace) down to the 10 parts-per-billion level. During selected ion flow tube mass spectrometry investigation of the volatile compounds emitted by urine, high acetone levels were incidentally identified in the headspace of urine from healthy female volunteers around their mid-cycle. Hence, this study was designed to measure urine headspace acetone levels throughout the menstrual cycle. METHODS: Using selected ion flow tube mass spectrometry we measured daily urine headspace acetone concentrations of seven ovulating (group 1) and three postmenopausal volunteers (group 2). RESULTS: A several-fold increase in urine headspace acetone level was detected 2-3 days after the predicted day of ovulation in 5 of the 7 volunteers in group 1. No such rise was detected in group 2. CONCLUSION: This study provides the basis for future research to understand the reason for and the potential utility of this phenomenon.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) has been used to measure simultaneously the concentrations of both carbon disulphide and acetone in exhaled breath following the ingestion of a single dose of disulfiram (Antabuse). Carbon disulphide is a product of the metabolism of disulfiram and is excreted mainly through the lungs. Acetone is a product of normal metabolism and appears in the breath of all individuals. These breath analyses were performed in single exhalations and the results were available in real time. The levels of breath acetone and carbon disulphide were compared with levels obtained from a control subject who had not ingested disulfiram. Breath carbon disulphide was seen to increase from 15 p.p.b. to 618 p.p.b. over a 28-hour period, in the single individual tested, following ingestion of disulfiram, while acetone levels increased from 300 p.p.b. (normal) to over 4000 p.p.b. (greatly elevated). No such increases were seen in the breath of the control subject over the same period. An obvious positive correlation between breath carbon disulphide and acetone concentrations following disulfiram ingestion is seen and discussed.

Abstract: Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volunteers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H3O+ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard deviation of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to providing the breath samples, but no increase was apparent when alcohol had been consumed the previous evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clinical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde).

Abstract: The increase in ammonia and ethanol in the exhaled breath stream following mouthwashes by aqueous solutions of urea and sugar (sucrose), respectively, has been investigated by analysing exhaled breath in real time using selected ion flow tube mass spectrometry, SIFT-MS. It is shown that the measured levels of these compounds in the stream of exhaled breath can be much greater than the endogenous levels originating at the alveolar boundary. Thus, it is concluded that without careful preparation, mouth production of these compounds, and other compounds as yet unidentified, can seriously compromise the quantification of truly endogenous trace compounds present in blood and in the alveolar breath, as required for clinical diagnosis, and can probably introduce additional compounds into the breath stream that could seriously mislead breath analysis. The concentrations of both the urea and sucrose solutions used to enhance the ammonia and ethanol levels were larger than normally present in food and drinks and so in most situations such severe enhancements will not occur.

Abstract: Thirty volunteers (19 males, 11 females) were recruited for a 6-month study of the volatile compounds in their exhaled breath using the selected ion flow tube mass spectrometry (SIFT-MS) analytical technique. Volunteers provided weekly breath samples between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper, we focus on the isoprene in alveolar breath, which was monitored by SIFT-MS using NO(+) precursor ions. The mean isoprene level for all samples was 118 parts per billion (ppb) with a standard deviation of 68 ppb and the range of values for breath samples given is 0-474 ppb. Variability in isoprene levels was similar in most volunteers. Isoprene levels increased immediately after moderate exercise, but returned to normal within 2-3 min for those few volunteers that were investigated. Cholesterol levels analysed for only three of the subjects were not obviously correlated with isoprene concentration in breath. Differences in isoprene levels were not directly correlated to gender, age or body mass index.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) is a technique that is well suited to the real-time analysis of head-space. SIFT-MS gives a non-discriminatory snapshot of the volatiles present and their amounts, and is considered to display less bias than chromatographic techniques as neither sample pre-treatment nor separation are necessary in most cases. The technique has been used for analysis of virgin olive oil head-space on more than 100 different oils. Twenty of these are reported. The results obtained using this technique differ from those normally reported from chromatographic analyses in that the dominant species in the head-space of all oils tested were methanol and ethanol. These volatiles were present in the head-space in the concentration ranges of 2.8-11.3 ppm (methanol) and 0.4-4.9 ppm (ethanol). (E)-2-Hexenal, normally reported as the dominant olive oil volatile, is found in significantly lower concentrations and is in the range of 0.02-1.6 ppm.

Abstract: We describe a new method, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) for the rapid and sensitive real-time detection and quantification of volatile organic compounds from medically important fungi, grown on a range of laboratory media. SIFT-MS utilises the chemical ionisation reactions of mass-selected ions to characterise volatile organic compounds (VOCs) that are produced as metabolites from fungi. This technique has the distinct advantage over others in that it readily detects low molecular weight, reactive volatiles, and allows for real-time, quantitative monitoring. The fungi examined in this study were Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Mucor racemosus, Fusarium solani, and Cryptococcus neoformans grown on or in malt extract agar, Columbia agar, Sabouraud's dextrose agar, blood agar, and brain-heart infusion broth. Common metabolites (ethanol, methanol, acetone, acetaldehyde, methanethiol, and crotonaldehyde) were detected and quantified. We found the fingerprint of volatiles, in terms of presence and quantity of volatiles to be strongly dependent on the culture medium, both in terms of variety and quantity of volatiles produced, but may form the basis for species specific identification of medically important fungi.

Abstract: A coordinated study of the dispersal of water between the various body compartments (stomach and gut, blood stream and tissue) and the similar dispersal kinetics of ethanol and its metabolism has been carried out involving two healthy volunteers using flowing afterglow mass spectrometry, FA-MS, and selected ion flow tube mass spectrometry, SIFT-MS. Thus, using these techniques, the variations of HDO and ethanol in breath, measured in successive single exhalations, were followed in real time after the ingestion of measured quantities of D2O and ethanol in proportion to the body weights of the subjects at the dose rates D2O approximately 0.283 g kg-1, ethanol approximately 0.067 g kg-1. During the FA-MS experimental periods (about 2 h), the dispersion of HDO into the body water and finally its equilibration in the total body water is observed from which total body water for each subject was determined. In the SIFT-MS measurements, the dispersion of ethanol into the body water and its loss via metabolism was observed until the physiological (pre-dose) breath level of ethanol for each individual was restored. A simple linear transformation is used to derive the time variations of the blood levels of HDO and ethanol. This has allowed a comparison of the fractions of the ingested ethanol that are metabolized during first-pass metabolism for the two subjects. Thus, in one subject 30% and in the other subject 40% of the ingested alcohol is metabolized in the first 20 min following ingestion. The good time resolution allowed by non-invasive breath analysis ensures that the rates of processes such as ethanol metabolism can be accurately measured. Simultaneous measurements of breath acetaldehyde (largely formed via the ethanol metabolism) and acetone were also performed during the SIFT-MS single breath exhalations.

Abstract: Pseudomonas aeruginosa (PA) is associated with a distinctive smell produced by a combination of volatile compounds (VCs). Selected ion flow tube mass spectrometry (SIFT-MS) provides a novel and rapid methodology for rapid, accurate detection of trace quantities (parts per billion; ppb) of VCs in air. We studied the VCs produced by different isolates of PA cultures in vitro from patients with cystic fibrosis. Twenty-one patients with cystic fibrosis provided sputum and cough swab samples for culture. These were used to inoculate blood agar (BA) and Pseudomonas-selective media (PSM). These plates were incubated for 48 hr at 37 degrees C inside sealed plastic bags. The air surrounding the samples after 48 hr (headspace) was analyzed using SIFT-MS. PA growth was commonly associated with the production of significant quantities of VCs, notably hydrogen cyanide gas (HCN). This was detectable in the headspace of 15/22 of PA-positive samples. In contrast, it was only seen in the headspace of 1/13 control samples (6 sterile plates and 7 plates with only mixed upper respiratory tract flora). The concentration of HCN was significantly higher above PA-positive samples than above other bacterial growth (P < 0.01), and in our study, levels of HCN greater than 100 ppb were a sensitive (68%) and highly specific (100%) biomarker of PA. SIFT-MS can detect a range of VCs from PA in vitro. HCN may be a specific indicator of PA infection in vivo, and offers promise as a biomarker for noninvasive detection of PA infection by breath analysis.

Abstract: The three-pore model of peritoneal membrane physiology predicts sieving of small solutes as a result of the presence of a water-exclusive pathway. The purpose of this study was to measure the diffusive and convective components of small solute transport, including water, under differing convection. Triplicate studies were performed in eight stable individuals using 2-L exchanges of bicarbonate buffered 1.36 or 3.86% glucose and icodextrin. Diffusion of water was estimated by establishing an artificial gradient of deuterated water (HDO) between blood/body water and the dialysate. (125)RISA (radio-iodinated serum albumin) was used as an intraperitoneal volume marker to determine the net ultrafiltration and reabsorption of fluid. The mass transfer area coefficient (MTAC) for HDO and solutes was estimated using the Garred and Waniewski equations. The MTAC of HDO calculated for 1.36% glucose and icodextrin were similar (36.8 versus 39.7 ml/min; P = 0.3), whereas for other solutes, values obtained using icodextrin were consistently higher (P < 0.05). A significant increase in the MTAC of HDO was demonstrated with an increase in the convective flow of water when using 3.86% glucose (mean value, 49.5 ml/min; P < 0.05). MTAC for urea was also increased with 3.86% glucose. The identical MTAC for water using 1.36% glucose and icodextrin indicates that diffusion is predominantly through small pores, whereas the difference in MTAC for the remaining solutes is a reflection of their sieving. The increase in the MTAC of water and urea associated with an increase in convection is most likely due to increased mixing within the interstitium.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) is a new analytical technique for the real-time quantification of several trace gases simultaneously in air and breath. It relies on chemical ionization of the trace gas molecules in air/breath samples introduced into helium carrier gas using H(3)O(+), NO(+), and O(2) (+.) precursor ions. Reactions between the precursor ions and trace gas molecules proceed for an accurately defined time, the precursor and product ions being detected and counted by a downstream mass spectrometer, thus effecting quantification. Absolute concentrations of trace gases in single breath exhalation can be determined by SIFT-MS down to ppb levels, obviating sample collection and calibration. Illustrative examples of SIFT-MS studies include (i) analysis of gases from combustion engines, animals and their waste, and food; (ii) breath and urinary headspace studies of metabolites, ethanol metabolism, elevated acetone during ovulation, and exogenous compounds; and (iii) urinary infection and the presence of tumors, the influence of dialysis on breath ammonia, acetone, and isoprene, and acetaldehyde released by cancer cells in vitro. Flowing afterglow mass spectrometry (FA-MS) is briefly described, which allows on-line quantification of deuterium in breath water vapor.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) has been used to analyse on-line and in real time the exhaust gas emissions from a Caterpillar 3304 diesel engine under different conditions of load (idle and 50% of rated load) and speed (910, 1500 and 2200 rpm) using three types of fuel: an ultra-low-sulphur diesel, a rapeseed methyl ester and gas oil. SIFT-MS analyses of the alkanes, alkenes and aromatic hydrocarbons in the headspace of these fuels were also performed, but the headspace of the rapeseed methyl ester consists mainly of methanol and a compound with the molecular formula C4H8O. The exhaust gases were analysed for NO and NO2 using O2+* reagent ions and for HNO2 using H3O+ reagent ions. The following aldehydes and ketones in the exhaust gases were quantified by using the combination of H3O+ and NO+ reagent ions: formaldehyde, acetaldehyde, propenal, propanal, acetone, butanal, pentanal, butanone and pentanone. Formaldehyde, acetaldehyde and pentenal, all known respiratory irritants associated with sensitisation to asthma of workers exposed to diesel exhaust, are variously present within the range 100-2000 ppb. Hydrocarbons in the exhaust gases accessible to SIFT-MS analyses were also quantified as total concentrations of the various isomers of C3H4, C3H6, C4H6, C5H8, C5H10, C6H8, C6H10, C7H14, C6H6, C7H8, C8H10 and C9H12.

Abstract: Following our recent observation that Pseudomonas bacteria in vitro emit hydrogen cyanide, we have found it necessary to investigate the ion chemistry of this compound and to extend the kinetics database for selected ion flow tube mass spectrometry (SIFT-MS) to allow the accurate quantification of HCN in moist air samples, including exhaled breath. Because of the proximity of the proton affinities of HCN and H2O molecules, the presence of water vapour can significantly distort HCN analysis in the presence of water vapour and a more sophisticated analytical procedure has to be developed. Thus, the reactions of H3O+(H2O)0,1,2,3 ions with HCN molecules have been studied in the presence of varying concentrations of water vapour, reactions on which SIFT-MS analysis of HCN relies. The results of these experiments have allowed an analytical procedure to be developed which has extended the kinetics database of SIFT-MS, such that HCN can now be quantified in humid air and in exhaled breath.

Abstract: The new technique of selected ion flow tube-mass spectrometry (SIFT-MS) has been applied to the measurement of Henry's Law constants for the volatile organic chemicals o-xylene and trichloroethylene that both have low solubility in aqueous solvents. The method is validated by measurements in water at 298 K using the equilibrium partitioning in closed systems (EPICS) methodology in which the equilibrium headspace concentrations for the volatile organic compounds (VOCs) are measured in two sealed bottles containing different liquid volumes of very dilute solutions of the VOC. The range of solvents is then extended to human body fluids at 309 K including urine, saline, whole blood, red cells in saline, and plasma. The dimensionless distribution coefficients for these solvents vary markedly in the different fluids. For o-xylene they range from k(H) = 0.12-0.15 for water, saline, and urine; 0.53 for red cells in saline; 1.9 for whole blood; to 2.4 for plasma. For trichloroethylene the distribution coefficients range from k(H) = 0.070-0.091 for water, saline, and urine; 0.28 for red cells in saline; 0.35 for plasma; to 0.48 in whole blood. The very different solubilities of organic solvents in body fluids influence the uptake of solvents in workers exposed to VOCs. Some implications of these measurements are briefly discussed.

Abstract: INTRODUCTION: Mechanisms of water flow across the peritoneal membrane include diffusion, convection, and reabsorption. OBJECTIVES: To understand these processes more clearly we have developed a method to measure transport of water across the peritoneal membrane. METHODS: An artificial gradient of deuterated water (HDO) between blood and dialysate compartments was created in five subjects who took 0.3g per kg of body weight of D2O, which was allowed to equilibrate with total body water. During a test dwell (2 L, bicarbonate:lactate buffer, 1.36% glucose to minimize convection), frequent dialysate samples were drawn to determine the abundance of deuterium and other solutes and to calculate their time constants. Dialysate deuterium abundance was measured using flowing afterglow mass spectrometry (FA-MS). The method was combined with 125iodine-labeled albumin (RISA) to enable simultaneous estimates of intraperitoneal volume and thus calculation of the mass transfer area coefficient (MTAC) for small solutes using the Garred equation. RESULTS: The appearance of HDO in dialysate in four subjects is described by a single exponential fit with residuals of <1%, similar to method precision. In a fifth subject, the resolution of this method demonstrated that the best fit was a double exponential. When compared to other solutes, the time constant for water was as predicted by its molecular weight, with a MTAC of 38.7 +/- 4.4 mL/min. Total body water could also be estimated from the equilibrated dialysate deuterium abundance, with repeat estimates within 0.5%. CONCLUSION: Transport of water across the peritoneum can be measured with remarkable accuracy and when combined with an intraperitoneal volume estimation can be used to determine mass transfer. In conditions of low convection, the relative rate of deuterium appearance and mass transfer compared to other solutes suggests that water diffuses predominantly through the intercellular small pores.

Abstract: A study of the concentrations of the common breath metabolites ammonia, acetone, isoprene, ethanol and acetaldehyde in the breath of five subjects over a period of 30 days has been carried out. Breath samples were taken and analysed in the early morning on arrival at the laboratory. The real time analyses of three consecutive breath exhalations were carried out using selected ion flow tube mass spectrometry (SIFT-MS) on line to the instrument. Sufficient data were obtained to allow meaningful concentration distributions to be obtained for ammonia, acetone, isoprene and ethanol. These showed that the ammonia, acetone and isoprene concentrations exhibited sensibly normal distributions, with coefficients of variation of typically 0.3. Obvious and statistically significant (p < 0.01) differences are apparent in the mean concentrations of these metabolites between the five individuals. The acetaldehyde concentrations were relatively low and close to the instrument detection limit, and the differences between the mean concentrations of the five subjects were not statistically significant (p = 0.4), so distributions were not obtained. The mean concentrations, in parts per billion (ppb), of each metabolite range amongst the five subjects are as follows: ammonia, 422-2389: acetone, 293-870; isoprene, 55-121; ethanol, 27-153; acetaldehyde, 2-5. There are no obvious patterns in the distributions of these particular metabolites for these individuals, except that the ammonia levels were greatest in the breath of the two oldest subjects.

Abstract: The production of volatile compounds from cancer cell lines in vitro has been investigated using selected ion flow tube mass spectrometry (SIFT-MS). This technique enables on-line quantitative analyses of the headspace above cell/medium cultures. This paper reports the discovery that acetaldehyde is released by the lung cancer cell lines SK-MES and CALU-1. The concentration of acetaldehyde in the headspace of the medium/cell culture was measured after 16 h incubation at 37 degrees C and found to be proportional to the number of cancer cells in the medium (typically 10(8)). From these data, the acetaldehyde production rates of the SK-MES cells and the CALU-1 cells in vitro are determined to be 1 x 10(6) and 1.5-3 x 10(6) molecules/cell/min, respectively. The potential value of this new technique in cell biology and in industrial cell biotechnology is discussed.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) has been used for a detailed study of the daily variations in the acetone and ammonia content of the headspace above urine from a healthy female subject over the course of three separate menstrual cycles. Midstream urine samples were taken every morning prior to any food intake and the headspace subsequently analysed for a number of metabolites. Concurrent with the time of ovulation, a 3-to- 12-fold increase in the level of acetone in the urine headspace was observed. The successive peaks in acetone level and the subsequent return to baseline values were mirrored by similar increases in the ammonia levels, but these were a day out of phase. Interestingly, parallel breath analyses at ovulation showed no great increase in either acetone or ammonia above their normal morning levels, suggesting that these metabolites had been removed from the body during the night by the usual metabolic and physiological processes. The results of this study reveal what may be an important phenomenon at the time of ovulation and illustrate the potential and power of online SIFT-MS analysis in this area of research.

Abstract: A selected ion flow tube mass spectrometry (SIFT-MS) study of the reactions of H3O+, NO+ and O2+* ions with the ketones (M) 2-heptanone, 2-octanone, 2-nonanone, 2-undecanone and 2-aminoacetophenone has been conducted in preparation for studies of volatile emissions from bacteria. The H3O+ reactions all proceed rapidly via exothermic proton transfer, producing only MH+ ions that form their monohydrates when water vapour is present in the helium carrier gas. The O2+* reactions proceed rapidly via dissociative charge transfer producing parent cations M+* and some fragment ions. The NO+ reactions form the NO+M adduct ions at rates which are dependent on the pressure of the helium carrier gas. Combining the present NO+ kinetic data with those available from previous SIFT studies, the phenomenon of charge transfer complexing is clearly demonstrated. This results in adduct formation in these NO+/ketone reactions at or near the collisional rate. SIFT-MS spectra are presented to illustrate the simplicity of SIFT-MS analysis of ketones using both H3O+ and NO+ precursor ions.

Abstract: We describe a method by which the concentrations of volatile compounds in the headspace of their dilute aqueous solutions in sealed containers can be determined using on-line selected ion flow tube mass spectrometry (SIFT-MS). Thus, the changing number density of the molecules of the volatile compound in the carrier gas of the SIFT-MS instrument is described in terms of its changing flow rate as the pressure in the sealed container decreases during the sampling procedure. It is shown that the best analytical procedure is to determine the mean concentration of the trace gas in the liquid headspace over a given sampling time and relate this to the required concentration, which is the initial equilibrium concentration established before the pressure in the sealed container reduces significantly. To test the validity of this analytical approach, the headspace concentrations of acetaldehyde, ethanol and acetone above aqueous solutions of known concentrations have been determined. Hence, the Henry's Law constants for these compounds have been determined and found to agree with the published values. The confirmation of the quality of this sampling methodology combined with SIFT-MS for the analysis of volatile compounds in liquid headspace paves the way for the rapid analyses of biological liquids such as urine and serum for clinical diagnosis and physiological monitoring.

Abstract: BACKGROUND: We developed a new near-subject approach, using flowing afterglow-mass spectrometry (FA-MS) and deuterium dilution, which enables the immediate measurement of total body water (TBW) from single exhalations. OBJECTIVES: The objectives were to show the efficacy of the new FA-MS method in measuring TBW in healthy subjects and to compare these measurements with values derived from multifrequency bioelectrical impedance analysis, skinfold-thickness (SFT) measurements, and both recent and historical published regression equations. DESIGN: After baseline measurement of breath deuterium abundance, 24 healthy subjects ingested 0.3 g D(2)O/kg body wt. A second breath sample was taken after 3 h to measure the increase in deuterium, from which TBW was calculated. Bioelectrical impedance analysis was carried out with a multifrequency analyzer, and SFT was measured by a single trained observer. Methods were compared with the use of Pearson's correlation coefficient and Bland-Altman analyses. RESULTS: TBW measures obtained by all methods were highly correlated (r = 0.95-0.98, P < 0.001), especially those between FA-MS, SFT measurement, and recent regression equations. The mean values obtained were within 2% of those published for age-matched control subjects and varied by 1-6% when all methods were compared. Systematic bias was greatest when FA-MS was compared with bioelectrical impedance analysis, which tended to underestimate TBW in smaller, female subjects. No bias related to subject size was observed in a comparison of FA-MS with SFT measurement or with more recent regression equations. CONCLUSIONS: FA-MS is a simple and effective new approach to TBW measurement in healthy subjects. The difficulty of using population-derived equations to estimate TBW in individual subjects is emphasized.

Abstract: We have carried out a study of the reactions of H(3)O(+), NO(+) and O(2) (+), the commonly used precursor ions for selected ion flow tube mass spectrometry (SIFT-MS), with three anaesthetic gases, halothane, isoflurane and sevoflurane. The motivation for this study was to provide the necessary kinetic data that would allow the quantification of these anaesthetic gases in operating theatre air and in the breath of theatre staff and post-operative patients. A clear negative result from these experiments is that NO(+), although undergoing the simplest chemistry, is unsuitable for this SIFT-MS application. However, although the ion chemistry of H(3)O(+) and O(2) (+) with these compounds is very complex, there being several product ions in each reaction, many of which react rapidly with water molecules, monitor ions have been identified for all three anaesthetic gases when using H(3)O(+) and O(2) (+) as precursor ions. The detailed ion chemistry is discussed and the specific monitor ions are indicated. Hence, the feasibility of on-line breath monitoring is demonstrated by simple examples. These studies have opened the way to measurements in the clinical environment.

Abstract: Selected ion flow tube mass spectrometry, SIFT-MS, has been used to measure simultaneously the concentrations in exhaled breath of ethanol, acetaldehyde, ammonia, acetone and, routinely, water vapour, following the ingestion of various amounts of ethanol in 500 ml of water. These breath analyses were obtained from only single exhalations, the results being available immediately in real time. The breath ethanol reaches concentrations that are only approximately consistent with its dilution in blood and body water. For moderate ethanol doses the decay quickly exhibits first-order kinetics (a single exponential decay) whereas for relatively large ethanol doses, the initial decay of ethanol from the breath is slow, indicating saturation kinetics. For smaller doses, and following a meal, the breath ethanol increases only slightly indicating that it is largely metabolized in the stomach. We suggest that the time delay (following ethanol ingestion) before the breath ethanol begins to increase is an indicator of the gastric emptying rate. Then the rate of decay of ethanol from the breath/blood is related to its rate of metabolism subsequent to its dispersal into the body water. The much lower breath acetaldehyde levels correlate well with the ethanol levels indicating that it is mostly formed from the metabolism of the ethanol. The breath ammonia is seen to 'dip' following the water/alcohol drink and this is consistent with previous work in which this same phenomenon was observed following the ingestion of comparable volumes of liquid meals. The simultaneous breath acetone concentrations increase somewhat with time as is expected during the fasting state. The water vapour measurements are indicators of the precision and accuracy of the breath analyses, these being sufficient to show the differences between the breath (body) temperatures of the individuals of less than 1 degrees C. This study demonstrates the potential of SIFT-MS for non-invasive physiological measurement.

Abstract: As a prelude to investigations of the emission of metabolites from human cell lines in vitro, we have conducted a study using selected ion flow tube mass spectrometry (SIFT-MS) of the acetaldehyde and ethanol that appear in the headspace above a fermenting yeast/glucose/water mixture in sealed glass bottles at a temperature of 30 degrees C. A fixed quantity of yeast (10 mg) and varying amounts (2, 4, 8 and 16 mg) of both non-deuterated glucose and glucose-6,6-d2 in 5 mL of water were used and the emission of the acetaldehyde and the ethanol were observed as a function of time. The ethanol and acetaldehyde concentrations in the headspace were obtained from the magnitudes of their characteristic ions on the accumulated SIFT mass spectra and, when the deuterated glucose was used, characteristic singly and doubly deuterated ions were obvious. This study indicates, as expected, that ethanol is the major species generated and that acetaldehyde is a relatively minor component of the headspace and a very minor component of the liquid phase. We estimate that about 10(8) ethanol molecules are produced per minute per cell in this yeast fermentation process. The distribution of the non-deuterated and partially deuterated ethanol under these fermentation conditions is observed to be C2H5OH (66 +/- 4)%, C2H4DOH(6 +/- 1)%, C2H3D2OH(28 +/- 4)%, and the analogous distribution for the acetaldehyde is the same, within error. These results indicate that the D atoms in the glucose-6,6-d2 are mostly retained by the 6-C atom, but the appearance of the singly deuterated ethanol and acetaldehyde indicates that some D/H mixing must be occurring in the enzymatic reactions. The results of this study illustrate the potential and power of on-line SIFT-MS analysis in this area of research.

Abstract: We report measurements of residual vapour levels of xylenes and trimethylbenzenes, present following a floor re-surfacing procedure, using the technique of selected ion flow tube mass spectrometry (SIFT-MS). A subject exposed to controlled amounts of xylene and mesitylene was monitored by direct breath exhalation over a 4-hour period after exposure to the volatile organic compounds (VOCs) had stopped. The headspace gases above 5 mL blood samples taken over this period were also monitored. The decays of the solvent levels with time were fitted to a two-compartment model with residence times for xylene and mesitylene of 0.37 h and 0.38 h, respectively (compartment one) and 2.5 h and 2.8 h, respectively (compartment two).

Abstract: A new technique is presented for the rapid, high-resolution identification and quantification of multiple trace gases above soils, at concentrations down to 0.01 microL L(-1) (10 ppb). The technique, selected ion flow tube mass spectrometry (SIFT-MS), utilizes chemical ionization reagent ions that react with trace gases but not with the major air components (N2, O2, Ar, CO2). This allows the real-time measurement of multiple trace gases without the need for preconcentration, trapping, or chromatographic separation. The technique is demonstrated by monitoring the emission of ammonia and nitric oxide, and the search for volatile organics, above containerized soil samples treated with synthetic cattle urine. In this model system, NH3 emissions peaked after 24 h at 2000 nmol m(-2) s(-1) and integrated to approximately 7% of the urea N applied, while NO emissions peaked about 25 d after urine addition at approximately 140 nmol m(-2) s(-1) and integrated to approximately 10% of the applied urea N. The monitoring of organics along with NH3 and NO was demonstrated in soils treated with synthetic urine, pyridine, and dimethylamine. No emission of volatile nitrogen organics from the urine treatments was observed at levels >0.01% of the applied nitrogen. The SIFT method allows the simultaneous in situ measurement of multiple gas components with a high spatial resolution of < 10 cm and time resolution <20 s. These capabilities allow, for example, identification of emission hotspots, and measurement of localized and rapid variations above agricultural and contaminated soils, as well as integrated emissions over longer periods.

Abstract: We have used selected ion flow tube mass spectrometry (SIFT-MS) to analyse the vapours emitted by petrol and diesel fuels and the exhaust gases from petrol (spark ignition) and diesel (compression ignition) engine vehicles fitted with catalytic converters. Only those components of these media that have significant vapour pressures at ambient temperatures were analysed and thus particulates were obviously not detected. These media have been analysed using the full scope of SIFT-MS, i.e., with the three available precursor ions H3O+, NO+ and O2+. The combination of the H3O+ and NO+ analyses is seen to be essential to distinguish between different product ions at the same mass-to-charge ratio (m/z) especially in identifying aldehydes in the exhaust gases. The O2+ precursor ions are used to detect and quantify the large amount of nitric oxide present in the exhaust gases from both engine types. The petrol and diesel vapours consist almost exclusively of aliphatic alkanes, alkenes and alkynes (and dienes) and aromatic hydrocarbons. Some of these compounds appear in the exhaust gases together with several aldehydes, viz. formaldehyde, acetaldehyde, pentanal, pentenal (acrolein), butenal, and also methanol and ethanol. Acetone, nitric oxide and ammonia are also present, acetone and nitric oxide being much more abundant in the diesel exhaust gas than in the petrol exhaust gas. These data were obtained from samples collected into pre-evacuated stainless steel vessels. Trapping of the volatile compounds from the gas samples is not required and analysis was completed a few minutes later. All the above compounds are detected simultaneously, which demonstrates the value of SIFT-MS in this area of research.

Abstract: We report the results of a flowing afterglow ion source-selected ion flow tube study (FA-SIFT) of the reactions of the methoxymethyl cation, CH3OCH2+. Rate coefficients and product branching ratios are reported for twenty nine reagent molecules including those that constitute the major ingredients of air, the hydrocarbons CH4, C2H6, C3H8, n-C4H10, C2H2, C2H4, C3H4 (allene and propyne), C6H6, and the S-containing molecules H2S, CH3SH, C2H5SH, (CH3)2SH, and (C2H5)2SH. In addition, we examined the reactions with the N-containing molecules NH3, CH3NH2, (CH3)2NH, (CH3)3N, pyrrole, pyridine as well as CH3COCH3. The results can be summarized under three general reaction types: Reaction at the CH3 carbon, reaction at the CH2 carbon, and association. The results also indicate that the methoxymethyl cation can be used as a chemical ionization source for the detection of trace levels of S-containing compounds in saturated hydrocarbons.

Abstract: In this paper we compare the amounts of ethanol in breath and in blood after ingestion of whisky using analysis by selected ion flow tube mass spectrometry (SIFT-MS). Blood ethanol concentrations were also obtained using standard hospital forensic procedures for blood alcohol analyses. We demonstrate the quantitative nature of SIFT-MS analysis by correlating the observed alcohol content of the headspace above 5-mL amounts of venous blood and aqueous solution to which known trace amounts of alcohol have been added. This procedure provides a Henry's Law coefficient for ethanol in aqueous solution at 298 +/- 3 K of 209 +/- 7 mol/kg*bar. We also demonstrate that measurement of the ethanol concentration in the alveolar portion of a single breath using the SIFT-MS technique gives an accurate measure of blood alcohol and could obviate the need for blood samples in forensic processing. The storage performance of breath samples in Mylar bags with a volume greater than 1 L has been shown to maintain the mixture integrity for ethanol but not for some other species.

Abstract: The selected ion flow tube mass spectrometry (SIFT-MS) technique enables real time analysis of trace volatiles at ppb levels without preconcentration steps or chemical derivatization. Most previous studies of trace compounds on the breath were analyzed using gas chromatography where enhanced detection sensitivity was achieved by concentrating the breath using cryogenic or adsorption trapping techniques. In this paper, we have examined volatile organic substances, isoprene, acetone, ammonia and ethanol in breath before and after smoking a cigarette. It is interesting that isoprene levels increased in all the subjects after smoking one cigarette with a mean increase of 70%. The mean increase for acetone was found to be 22%. In contrast to isoprene, a decreasing ethanol level was observed in all the subjects except one with the negative mean decrease of 28%. Further SIFT-MS studies also have high-lighted some organic substances produced even by unburned cigarettes, US and New Zealand products. Certain US brands have shown much higher levels of volatile species than cigarettes produced in New Zealand.

Abstract: This work investigated the potential to use measurement of the concentration of certain gases in the rumen headspace to gain information about rumen processes and as a potential diagnostic tool. We used new equipment (selected-ion-flow-tube mass spectrometer) that allows rapid and precise analysis of many of the gases present in a sample. Samples of rumen headspace gas and corresponding samples of rumen liquor were taken from three lactating cows, prepared with rumen fistulae, at intervals after receiving their morning feed allocation (grass silage and concentrates). Hydrogen sulfide, methyl sulfide, and dimethyl sulfide, were the predominant gases that were measured in the rumen headspace by this technique. The concentrations of these sulfur compounds declined over the interval after feeding, mirroring ammonia concentrations measured in rumen liquor, reflecting their common dependence on the fermentation of sulfur amino acids. Ammonia concentrations in rumen headspace gas varied in the opposite direction to the concentration of ammonia in rumen liquor and likely depend more on the pH of rumen liquor. Consideration of the pKa of ammonia suggests that ammonia concentrations in rumen gas will be very low below pH 6, representing a useful diagnostic for subacute ruminal acidosis. Low concentrations of volatile fatty acids were detected in rumen gas. The molar proportions of volatile fatty acids were similar in gas and liquor samples, with rumen gas containing slightly less acetic acid and disproportionately more valeric and caproic acids.

Abstract: BACKGROUND: Isoprene is the most abundant hydrocarbon present in breath, and recent reports indicate that breath concentrations increase following haemodialysis. The purpose of this study was to establish whether selected ion flow tube mass spectrometry (SIFT-MS), a newly established technique in breath analysis, may be used to quantify breath isoprene in haemodialysis patients in the clinical setting. SIFT-MS is compared and contrasted with the established gas chromatography mass spectrometric technique for this purpose. METHODS: Three consecutive exhalations from 19 haemodialysis patients (12 males, seven females) undergoing a morning dialysis shift were analysed just prior to commencing treatment. Within 5 min of completing their usual dialysis regimen, using polysulphone membranes, the breath of each patient was analysed again. Additional contemporary samples were obtained from 17 normal controls. Breath isoprene was quantified using SIFT-MS, a method previously validated quantitatively using neat isoprene. RESULTS: Successful measurements of breath isoprene were obtained for each subject within 2 min, with minimum disruption to a busy dialysis environment. The coefficient of variation of triplicate measurements of breath isoprene was <10%. Prior to dialysis, the mean (+/-SD) breath isoprene concentration (138+/-63 parts per billion (ppb)) was significantly greater than for normal controls (89+/-36 ppb; P=0.016). Immediately following treatment, breath isoprene increased significantly to 184+/-95 ppb (P=0.023). CONCLUSIONS: SIFT-MS permits the accurate and rapid measurement of breath isoprene in haemodialysis patients in the clinical setting. The previously reported increase in breath isoprene following dialysis treatment is confirmed. SIFT-MS is the ideal analytical tool to investigate this phenomenon further.

Abstract: We have developed a new method for the on-line quantification of deuterium in water vapour. We call this method flowing afterglow mass spectrometry (FA-MS). A swarm of H3O+ precursor ions is created in flowing helium carrier gas by a microwave discharge. These precursor ions react with the H2O, HDO, H2(17)O and H2(18)O molecules in a water vapour sample that is introduced into the carrier gas/H3O+ ion swarm. The hydrated ions, H3O+.(H2O)3 at m/z 73, and their isotopic variant ions H8DO4(+) and H9(17)OO(3)(+) at m/z 74 and H9(18)OO(3)(+) at m/z 75, are thus formed. By adopting the known fractional abundance of 18O in water vapour, and accounting for the contribution of the isotopic ions H9(17)OO(3)(+) to the ion signal at m/z 74, a measurement of the 74/75 ion signal ratio under equilibrium conditions provides the fractional deuterium abundance in the water vapour sample. Using this technique, the deuterium abundance in the water vapour present in single exhalations of breath can be determined. Thus, from the temporal variations of breath deuterium following the ingestion of a known quantity of D(2)O, we show that total body water can be determined non-invasively and the kinetics of water flow around the body can be tracked.

Abstract: We describe how selected ion flow tube mass spectrometry (SIFT-MS) can be used to determine the absolute humidity of air, breath and liquid headspace samples. This involves the determination of the relative count rates of the H3O+ ions and those H3O+.(H2O)(1,2,3) hydrate ions that inevitably form in the helium carrier gas when humid samples are being analysed by SIFT-MS using H3O+ precursor ions. This requires an understanding of the kinetics of hydrated hydronium ion formation, the involvement of mass discrimination in the analytical quadrupole mass spectrometer and the decreased diffusive loss of the heavier hydrates along the flow tube. Thus, we show that the humidity of breath and liquid headspace samples, typically at the few percent level, can be directly obtained on-line to the SIFT-MS instrument along with the concentrations of trace gases, which are present at much lower levels. We emphasise the value of parallel humidity measurements in ensuring good real-time sampling of breath and liquid headspace and the value of such measurements to trace gas analysis using SIFT-MS.

Abstract: We have assessed the accuracy and precision of our flowing afterglow mass spectrometric method (FA-MS) for absolute measurements of deuterium abundance in water using standardised tap water/D(2)O mixtures within the D/H range from 155 ppm (local tap water) to 1104 ppm, prepared by the gravimetric method. The results of this study show that a precision and accuracy of 1% can be achieved for the deuterium abundance in water samples. This is quite adequate for the main application, which is the rapid, non-invasive measurement of total body water by deuterium analysis of breath water vapour using the D(2)O dilution method.

Abstract: The ability to measure total body water accurately, non-invasively and rapidly with results that are immediately available would represent an important advance in body composition research. Flowing afterglow mass spectrometry (FA-MS) has been developed to enable immediate measurement of deuterium content in breath water from single exhalations, which when combined with oral D2O loading enables measurement of total body water. We report here its first use in normal subjects, demonstrating the dispersal kinetics of deuterium in the body by monitoring deuterium in breath water following ingestion. Ten studies were performed in six normal subjects. After obtaining baseline samples, each subject ingested 0.3 g x kg(-1) of 99.9% pure D2O. Subsequently, breath samples were obtained every 3-5 minutes until equilibration had occurred. Three distinct phases in breath deuterium content were observed: an initial immediate peak due to HDO remaining in the oral cavity, a secondary peak reflecting gastrointestinal absorption and finally equilibration with the body water. The incremental increase in breath deuterium abundance between baseline and equilibration was used to calculate the total body water. Mathematical fitting of this final equilibration phase demonstrated that the measured deuterium abundance was within 0.2% of the ideal (asymptotic) value within 2 hours in all cases. We conclude that FA-MS is a powerful new method that, when combined with oral D2O loading, enables measurement of the dispersal kinetics of HDO and the calculation of total body water within 2 hours.

Abstract: Selected ion flow tube mass spectrometry, (SIFT-MS), involves the partial conversion of mass-selected precursor ions to product ions in their reactions with the trace gases in an air sample that is introduced into helium carrier gas in a flow tube. The precursor and product ions are then detected and counted by a downstream quadrupole mass spectrometer. Quantification of particular trace gases is thus achieved from the ratio of the total count rate of the product ions to that for the precursor ions. However, it is important to appreciate that in this ion chemistry the light precursor ions (usually H3O+ ions) are invariably converted to heavier product ions. Hence, the product ions diffuse to the flow tube walls more slowly and thus they are more efficiently transported to the downstream mass spectrometer sampling orifice. This phenomenon we refer to as diffusion enhancement. Further, it is a well-known fact that discrimination can occur against ions of large mass-to-charge ratio, (m/z), in quadrupole mass spectrometers. If not accounted for, diffusion enhancement usually results in erroneously high trace gas concentrations and mass discrimination results in erroneously low concentrations. In this experimental investigation, we show how both these counteracting effects can be accounted for to increase the accuracy of SIFT-MS quantification. This is achieved by relating the currents of ions of various m/z that arrive at the downstream mass spectrometer sampling orifice disc to their count rates at the ion detector after mass analysis. Thus, both diffusion enhancement and mass discrimination are parameterized as a function of m/z and these are combined to provide an overall discrimination factor for the particular analytical instrument.

Abstract: Selected ion flow tube mass spectrometry (SIFT-MS) detects and quantifies in real time the trace gases, M, in air/breath samples introduced directly into a flow tube. Inevitably, relatively large partial pressures of water vapour are introduced with the sample and the water molecules become involved in the ion chemistry on which this analytical technique depends. When H(3)O(+) ions are used as the precursors for chemical ionisation and SIFT mass spectrometric analyses of M, they generally result in the formation of MH(+) ions. Also, when water vapour is present the H(3)O(+) ions are partially converted to hydrated hydronium ions, H(3)O(+).(H(2)O)(1,2,3). The latter may act as precursor ions and produce new product ions like MH(+).(H(2)O)(1,2,3) via ligand switching and association reactions. This ion chemistry and the product ions that result from it must be accounted for in accurate analyses by SIFT-MS. In this paper we describe the results of a detailed SIFT study of the reactions involved in the quantification of acetone, ethyl acetate, diethyl ether, methanol, ethanol, ammonia and methyl cyanide by SIFT-MS in the presence of water vapour. This study was undertaken to provide the essential data that allows more accurate analyses of moist air and breath by SIFT-MS to be achieved. It is shown using our standard analysis procedure that the error of SIFT-MS quantification caused by the presence of water vapour is typically 15%. An improved analysis procedure is then presented that is shown to reduce this error to typically 2%. Additionally, some fundamental data have been obtained on the association reactions of protonated organic molecules, MH(+) ions, with water molecules forming MH(+).H(2)O monohydrate ions. For some types of M, reaction sequences occur that lead to the formation of dihydrate and trihydrate ions.

Abstract: We show how the concentration of the breath gases ammonia, acetone, and isoprene vary with time during exercise using the new selected ion flow tube mass spectrometry (SIFT-MS) technique. The expired breath concentrations of ammonia, acetone and isoprene were observed within the range of 50-500, 100-1400 and 5-400 ppb, respectively. Increasing acetone levels were observed for most subjects during the exercise period. However, isoprene levels decreased with time during exercise. Older subjects showed higher levels of isoprene compared with younger subjects. The ammonia time profile with exercise showed both decreasing and increasing patterns for different subjects.

Abstract: A new method has been developed for the determination of the isotope abundance ratios of deuterium, D, and oxygen-18, 18O, in water vapor (and water) using selected ion flow tube mass spectrometry (SIFT-MS). H3O+ ions are injected into the helium carrier gas where they associate with the H2O and HDO molecules in a sample of water introduced into the carrier gas. The D and 18O contents of the product cluster ions H8DO4+ and H9(18)OO3+ at m/e = 74 and 75, respectively, are determined by reference to the majority cluster ion H9O4+ at m/e = 73. Allowance is made for the contribution of the H8(17)OO3+ ions to the m/z = 74 ions. Absolute isotopic ratios are measured within seconds without the need for precalibration of the SIFT-MS instrument, currently to an accuracy of better than 2%.

Abstract: We report the results of a study of the reactions of H(3)O(+), NO(+) and O(2)(+.) ions with H(2)S. This study was undertaken to provide a thorough understanding of the ion chemistry required for accurate quantification of H(2)S in humid air by selected ion flow tube mass spectrometry (SIFT-MS). It shows that slow reactions occur between H(3)S(+), the primary product ions of the H(3)O(+)/H(2)S reaction, and the abundant H(2)O molecules present in humid air and breath. These reactions disturb somewhat the quantification of H(2)S by this analytical method, but the kinetic data obtained in this study facilitate precise quantification of H(2)S in humid air. This study also shows that NO(+) does not react with H(2)S, and that O(2)(+.) does react rapidly with H(2)S, but the product H(2)S(+.) ions react rapidly with H(2)O. Thus, NO(+) and O(2)(+.) cannot be used as precursor ion for analysis of H(2)S in moist air by SIFT-MS. A sample SIFT mass spectrum is shown from which H(2)S and several other volatile compounds have been quantified in a sample of cow rumen gas.

Abstract: A selected ion flow tube (SIFT) experimental investigation has been carried out of the reactions of H3O+, NO+ and O2+ with NO, NO2, N2O and HNO2, in order to obtain the essential kinetic data for the analyses of these compounds in air using selected ion flow tube mass spectrometry (SIFT-MS). These investigations show that NO+ ions do not react at a significant rate with any of these NOx compounds and that H3O+ ions react only with HNO2 (product ions H2NO2+ (75%) and NO+ (25%)). O2+ ions react with NO (product ion NO+), NO2 (product ion NO2+) and HNO2 (product ions NO+ (75%), NO2+ (25%)), but not with N2O. We conclude that both NO and NO2 can be accurately quantified in air using only O2+ precursor ions and SIFT-MS when HNO2 is not present. However, when HNO2 is present it invariably co-exists with both NO and NO2 and then both H3O+ and O2+ precursor ions are needed to determine the partial pressures of NO, NO2 and HNO2 in the air mixture. We also conclude that currently N2O cannot be analysed in air using SIFT-MS.

Abstract: We have used selected ion flow tube mass spectrometry (SIFT-MS) to determine the concentration of formaldehyde in the headspace of urine from patients suffering from bladder and prostate cancer and from several healthy subjects as controls. We address the potential problems associated with the use of ion chemistry to quantify formaldehyde in the presence of the relatively large number densities of water molecules and show that formaldehyde can be quantified in urine headspace using analysis by SIFT-MS. These studies show that formaldehyde is clearly elevated in the headspace of the urine from the cancer patients as compared with urine from the healthy controls. Thus, with further improvements in the methodology and the sensitivity of our SIFT-MS technique, formaldehyde quantification in urine headspace using this new analytical method could be a valuable non-invasive indicator of the presence of early-stage tumours in the body.

Abstract: We have used our selected ion flow tube mass spectrometric method (SIFT-MS) to study isoprene levels in the alveolar breath of 29 healthy volunteers during normal working hours at the varying states of nutrition occurring during this period. Quantification of the breath isoprene was achieved using O(2)(+) precursor ions to avoid complications which can arise when using H(3)O(+) precursor ions for isoprene analysis. The present data indicate that the spread of the alveolar isoprene levels in this sample of healthy individuals is 22 to 234 ppb and that the mean value is 83 ppb with a standard deviation of 45 ppb. These levels are compared with those previously determined using other techniques and are seen to be at the low end of the values previously reported. The present studies are a prelude to an investigation of the proposed correlation of breath isoprene levels with psychological, physical and biochemical stress.

Abstract: We describe the use of our selected ion flow tube mass spectrometric technique (SIFT-MS) for the analysis of the headspace above urine. Ammonia, nitric oxide, acetone, ethanol and methanol are identified as the dominant species. As expected, the ammonia is increased in the headspace by making the urine alkaline and the nitric oxide is increased by making the urine acidic. Nitric oxide is abnormally high in the headspace of acidified bacterially infected urine and nitrous acid is also detected. The potential clinical implications of analyses of urine by SIFT-MS are alluded to.

Abstract: The selected ion flow tube technique was used to quantify in breath the trace gases acetone, ammonia, ethanol, isoprene, and methanol during single exhalations while fasting and in response to feeding. Six normal volunteers were fasted for 12 h, and, after baseline breath samples were obtained, were fed a liquid protein-calorie meal to provide 0.47 g/kg of protein (Fortisip). Further breath samples were obtained at 20, 40, and 60 min, and then hourly for a further 5 h. Breath acetone concentrations fell from a maximum during fasting, reaching their nadir between 4 and 5 h. Breath ammonia concentrations fell immediately to one-half their fasting levels before a steady increase to two or three times baseline values at 5 h. There was a brief increase in breath ethanol concentrations after feeding, reflecting detectable ethanol contamination of the food. Subsequently, breath ethanol levels remained low throughout the experimental protocol. Isoprene concentrations did not change significantly, whereas changes in methanol concentrations reflected those in the ambient air. This preliminary study indicates that the selected ion flow tube technique may be used to detect changes in the trace gases present in breath and define their concentrations in the fasting and replete state. Of particular interest is the biphasic response of the breath ammonia concentration after feeding.

Abstract: We show how our selected ion flow tube mass spectrometric technique for trace gas analysis can be used to determine the concentrations of ammonia in alveolar breath from single exhalations using both H30+ and 02+ precursor ions for chemical ionization. Thus, data are presented of the alveolar ammonia concentrations in the breath of six healthy volunteers following the ingestion of a liquid protein meal, which show that consistent values are obtained using these two precursor ions. Alveolar breath ammonia concentrations (which range from 200 to 1750 ppb in these individuals) are compared with those obtained from bag samples of breath from the same individuals.

Abstract: BACKGROUND: Oilseed rape has been associated by rural dwellers with seasonal symptoms, such as sneezing, coughing, headache and eye irritation, during its flowering season, for a number of years. This study was performed to identify the volatile chemicals emitted from oilseed rape in the field. OBJECTIVE: The objective of this study was to establish which volatile chemicals may be causative factors of oilseed rape allergy/toxicity. METHODS: The volatile organic compounds were sampled over the flowering period using a modified entrainment technique for headspace analysis under field conditions. These volatiles were then identified using thermal desorption-gas chromatography-mass spectrometry. RESULTS: The major constituents identified were the monoterpenes limonene, sabinene, beta-myrcene, and cis-3-hexen-l-ol acetate, a 'green leaf' volatile. The minor constituents included monoterpenes, sesquiterpenes, short chain aldehydes and ketones, other 'green leaf' volatiles and organic sulphides including the respiratory irritant, dimethyl disulphide. CONCLUSIONS: This report highlights the diversity of volatile chemicals emitted by oilseed rape and confirms field emissions to be broadly similar to those found previously in laboratory studies. A review is carried out on the scientific literature already published on oilseed rape flower headspace analysis.

Abstract:

Abstract: The selected ion flow tube (SIFT) technique for trace gas analysis of air and breath is based on soft chemical ionisation of the trace gases to the exclusion of the major air and breath gases, in fast-flowing inert carrier gas, exploiting the ion-molecule reactions that occur between the trace gases and the pre selected precursor ions (H3O+, NO+ and O2+). The physics and ion chemistry involved in the SIFT technique are described, as are the kinetics of the ion-molecule reactions that are exploited to quantitatively analyse the trace gases. Fast on-line data-acquisition hardware and software have been developed to analyse the mass spectra obtained, from which partial pressures of the trace gases down to about 10 parts per billion can be measured. The time response of the instrument is 20 ms, allowing the profiles of the trace gas concentrations on breath to be obtained during a normal breathing cycle. Pilot results obtained with this SIFT technique include detection and quantification of the most abundant breath trace gases, analysis of cigarette smoke, detection of gases present on smokers' breath and accurate measurement of the partial pressures of NH3, NO and NO2 in air. The simultaneous analysis of several breath trace gases during a single exhalation is clearly demonstrated, and thus different elution times for isoprene and methanol along the respiratory tract are observed. This technique has great potential in many clinical and biological disciplines, and in health and safety monitoring.

Abstract: We describe the use of our selected ion flow tube (SIFT) technique for the rapid detection and quantification of trace gases in atmospheric air, with special reference to the analysis of human breath. It is based on the chemical ionization of the breath trace gases to the exclusion of the major breath gases, using 'soft' proton transfer from H3O+ ions. Breath samples can either be introduced into the SIFT from bags or by direct breathing into the apparatus, the advantage of the latter approach being that surface active gases such as ammonia and many organic vapours which adsorb onto bag surfaces can be more accurately quantified. We present examples of the analysis of laboratory air, the breath of a non-smoker and of a smoker taken from bag samples, and illustrate the rapid time response of the technique by showing the time profile of acetone on breath during direct breathing into the apparatus. The current partial pressure sensitivity of our SIFT method is within the range 30 ppb to in excess of 100 ppm, but with further development the device could be made more sensitive, 1 ppb being well within reach. A transportable SIFT device is under development which will have applications in environmental, medical and biological research, health and safety monitoring, and in clinical diagnosis.

Abstract: We present an overview of the development and use of our selected-ion flow tube (SIFT) technique as a sensitive, quantitative method for the rapid, real-time analysis of the trace gas content of atmospheric air and human breath, presenting some pilot data from various research areas in which this method will find valuable application. We show that it is capable of detecting and quantifying trace gases, in complex mixtures such as breath, which are present at partial pressures down to about 10 parts per billion. Following discussions of the principles involved in this SIFT method of analysis, of the experiments which we have carried out to establish its quantitative validity, and of the air and breath sampling techniques involved, we present sample data on the detection and quantification of trace gases on the breath of healthy people and of patients suffering from renal failure and diabetes. We also show how breath ammonia can be accurately quantified from a single breath exhalation and used as an indicator of the presence in the stomach of the bacterium Helicobacter pylori. Health and safety applications are exemplified by analyses of the gases of the gases of cigarette smoke and on the breath of smokers. The value of this analytical method in environmental science is demonstrated by the analyses of petrol vapour, car exhaust emissions and the trace organic vapours detected in town air near a busy road. Final examples of the value of this analytical method are the detection and quantification of the gases emitted from crushed garlic and from breath following the chewing of a mint, which demonstrate its potential in food and flavour research. Throughout the paper we stress the advantages of this SIFT method compared to conventional mass spectrometry for trace gas analysis of complex mixtures, emphasizing its selectivity, sensitivity and real-time analysis capability. Finally, we note that whilst the current SIFT is strictly laboratory based, both transportable and portable instruments are under construction and development. These instruments will surely extend the application of this analytical technique into more areas and allow greater exploitation of their on-line and real-time features.

Abstract: Reactivities of the structural isomers CCN+ and CNC+ were examined in a selected-ion flow tube at 300 +/- 5 K. The less reactive CNC+ isomer was identified as the product of the reactions of C(+) + HCN and C(+) + C2N2; in these reactions only CNC+ can be produced because of energy constraints. Rate coefficients and branching ratios are reported for the reactions of each isomer with H2, CH4, NH3, H2O, C2H2, HCN, N2, O2, N2O, and CO2. Ab initio calculations are presented for CCN+ and CNC+; a saddle point for the reaction CCN+ --> CNC+ is calculated to be 195 kJ mol-1 above the CNC+. The results provide evidence that the more reactive CCN+ isomer is unlikely to be present in measurable densities in interstellar clouds.