Influence of water vapour on selected ion flow tube mass spectrometric analyses of trace gases in humid air and breath

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.     

Ambient analysis of trace compounds in gaseous media by SIFT-MS

The topic of ambient gas analysis has been rapidly developed in the last few years with the evolution of the exciting new techniques such as DESI, DART and EESI. The essential feature of all is that analysis of trace gases can be accomplished either in the gas phase or those released from surfaces, crucially avoiding sample collection or modification. In this regard, selected ion flow tube mass spectrometry, SIFT-MS, also performs ambient analyses both accurately and rapidly. In this focused review we describe the underlying ion chemistry underpinning SIFT-MS through a discourse on the reactions of different classes of organic and inorganic molecules with H(3)O(+), NO(+) and O(2)(+)˙ studied using the SIFT technique. Rate coefficients and ion products of these reactions facilitate absolute SIFT-MS analyses and can also be useful for the interpretation of data obtained by the other ambient analysis methods mentioned above. The essential physics and flow dynamics of SIFT-MS are described that, together with the reaction kinetics, allow SIFT-MS to perform absolute ambient analyses of trace compounds in humid atmospheric air, exhaled breath and the headspace of aqueous liquids. Several areas of research that, through pilot experiments, are seen to benefit from ambient gas analysis using SIFT-MS are briefly reviewed. Special attention is given to exhaled breath and urine headspace analysis directed towards clinical diagnosis and therapeutic monitoring, and some other areas researched using SIFT-MS are summarised. Finally, extensions to current areas of application and indications of other directions in which SIFT-MS can be exploited for ambient analysis are alluded to.     

Selected ion flow tube mass spectrometry for on-line trace gas analysis in biology and medicine

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.     

On-line measurement of the absolute humidity of air, breath and liquid headspace samples by selected ion flow tube mass spectrometry

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.     

Quantification of hydrogen sulphide in humid air by selected ion flow tube mass spectrometry

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.     

Selected ion flow tube studies of the reactions of H3O+, NO+ and O2+ with the anaesthetic gases halothane,isoflurane and sevoflurane

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.     

The analysis of 1-propanol and 2-propanol in humid air samples using selected ion flow tube mass spectrometry

Following the observation that propanol is present in the breath samples of cystic fibrosis (CF) patients infected by Pseudomonas aeruginosa (PA), a study of the reactions of H(3)O(+), NO(+) and O(2) (+.) with 1-propanol and 2-propanol has been conducted using selected ion flow tube mass spectrometry (SIFT-MS). In this study the number and the distribution of the product ions from NO(+) reactions with the two propanol isomers under humid air conditions were able to differentiate between the two isomers. The reaction mechanisms and the structures of the product ions for these reactions, especially those with H(3)O(+) and NO(+), have been proposed. As an example, 2-propanol was shown to be present in a breath sample from one CF patient infected with PA, and also in a PA isolate from another CF patient grown on Pseudomonas-selective media. The results of this study allow an analytical procedure to be advanced for the analysis of the two propanol isomers, which can also be utilised in other applications.     

Influence of weakly bound adduct ions on breath trace gas analysis by selected ion flow tube mass spectrometry (SIFT-MS)

This paper describes how weakly bound adduct ions form when the precursor ions used in selected ion flow mass spectrometry, SIFT-MS, analyses, viz. H₃O⁺, NO⁺ and O₂⁺, associate with the major components of air and exhaled breath, N₂, O₂ and CO₂. These adduct ions, which include H₃O⁺N₂, H₃O⁺CO₂, NO⁺CO₂, O₂⁺O₂ and O₂⁺CO₂, are clearly seen when dry air containing 5% CO₂ (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 H₃O⁺N₂ interfering with breath ethanol analysis and H₃O⁺CO₂ 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 O₂⁺CO₂ in the product ion spectra interferes with the analysis of CS₂ 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, H₃O⁺CH₄ adduct ions are observed in both SIFT-MS analyses of methane rich mixtures like biologically generated waste gases and in model planetary atmospheres.     

Combined use of gas chromatography and selected ion flow tube mass spectrometry for absolute trace gas quantification

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.     

On-line determination of the deuterium abundance in breath water vapour by flowing afterglow mass spectrometry with applications to measurements of total body water

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.     

The quantification of carbon dioxide in humid air and exhaled breath by selected ion flow tube mass spectrometry

The reactions of carbon dioxide, CO₂, with the precursor ions used for selected ion flow tube mass spectrometry, SIFT‐MS, analyses, viz. H₃O⁺, NO⁺ and O, are so slow that the presence of CO₂ 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, H₃O⁺CO₂, formed by the slow association reaction of the precursor ion H₃O⁺ with CO₂ 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 CO₂ in breath using the level of the H₃O⁺CO₂ adduct ion. However, this is complicated by the rapid reaction of H₃O⁺CO₂ with water vapour molecules, H₂O, 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 H₃O⁺ with CO₂ and its rapid loss in the two‐body reaction with H₂O molecules. It is seen that the signal level of the H₃O⁺CO₂ adduct ion is sensitively dependent on the humidity (H₂O 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 CO₂ 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 CO₂ 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. Copyright © 2009 John Wiley & Sons, Ltd.     

Analysis of ketones by selected ion flow tube mass spectrometry

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.     

On-line, real time monitoring of exhaled trace gases by SIFT-MS in the perioperative setting: a feasibility study

A study is described of the first on line, real time analyses of the exhaled breath of five anaesthetized patients during the complete perioperative periods of laparoscopic surgery. These breath analyses were achieved using a selected ion flow tube, SIFT-MS, instrument, located in the operating theatre at an acceptable distance from the operating table, and coupled to the endotracheal tube in the ventilation circuit via a 5 metre long capillary tube. Thus, inhalation/exhalation breathing cycles, set to be at a frequency of 10 per minute, were sampled continuously for water vapour, the metabolites acetone and isoprene and the propofol used to induce anaesthesia for each operating period that ranged from 20 min (shortest) to 80 min (longest). Whilst there was some loss of water vapour along the long sampling line, the concentrations of the other trace compounds were not diminished. The breath acetone was essentially at a constant level for each patient, but increased somewhat over the longest operating period due to the onset of lipolysis. Most interesting is the clear increase of breath isoprene following abdomen inflation with carbon dioxide. The vapour of the intravenously injected propofol was detected in the exhaled breath and remained essentially constant during the perioperative period. These analyses were performed totally non-invasively and the data were immediately and constantly available to the anaesthetist and surgeon. Exploitation of this development could influence decision making and potentially improve patient safety within the perioperative setting.     

选择离子流动管质谱及其在痕量气体分析中的应用

选择离子流动管质谱(SIFT-MS)结合流动管技术、化学电离和质谱,有选择地使用F13O^ 、NO^ 和O2^ 初始离子,可在几秒之内对空气、呼吸气体和液表蒸气中的痕量气(如乙醇、乙醛、丙酮、氨和2-甲基丁二烯等,行多组分实时在线分析。介绍了选择离子流动管(SIFT)技术、SIFT-MS的分析方法及其物理和离子化学基础、SIFT-MS在不同领域的痕量气体分析中的应用。     

Selected ion flow tube mass spectrometry of exhaled breath condensate headspace

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. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Direct, rapid quantitative analyses of BVOCs using SIFT-MS and PTR-MS obviating sample collection

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.     

Determination of the Deuterium Abundances in Water from 156 to 10,000 ppm by SIFT-MS

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, (16)O, (17)O and (18)O isotopes in the isotopologues of H(3)O(+)(H(2)O)(3) hydrated ions (i.e. H(9)O (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.     

Selected ion flow tube mass spectrometry analyses of stable isotopes in water: Isotopic composition of H3O+ and H3O+(H2O)3 ions in exchange reactions with water vapor

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%.     

Quantification of methane in humid air and exhaled breath using selected ion flow tube mass spectrometry

In selected ion flow tube mass spectrometry, SIFT‐MS, analyses of humid air and breath, it is essential to consider and account for the influence of water vapour in the media, which can be profound for the analysis of some compounds, including H₂CO, H₂S and notably CO₂. To date, the analysis of methane has not been considered, since it is known to be unreactive with H₃O⁺ and NO⁺, the most important precursor ions for SIFT‐MS analyses, and it reacts only slowly with the other available precursor ion, O. However, we have now experimentally investigated methane analysis and report that it can be quantified in both air and exhaled breath by exploiting the slow O/CH₄ reaction that produces CH₃O ions. We show that the ion chemistry is significantly influenced by the presence of water vapour in the sample, which must be quantified if accurate analyses are to be performed. Thus, we have carried out a study of the loss rate of the CH₃O analytical ion as a function of sample humidity and deduced an appropriate kinetics library entry that provides an accurate analysis of methane in air and breath by SIFT‐MS. However, the associated limit of detection is rather high, at 0.2 parts‐per‐million, ppm. We then measured the methane levels, together with acetone levels, in the exhaled breath of 75 volunteers, all within a period of 3 h, which shows the remarkable sample throughput rate possible with SIFT‐MS. The mean methane level in ambient air is seen to be 2 ppm with little spread and that in exhaled breath is 6 ppm, ranging from near‐ambient levels to 30 ppm, with no significant variation with age and gender. Methane can now be included in the wide ranging analyses of exhaled breath that are currently being carried out using SIFT‐MS. Copyright © 2010 John Wiley & Sons, Ltd.     

An investigation of the reactions of H3O+ and O2+ with NO, NO2, N2O and HNO2 in support of selected ion flow tube mass spectrometry

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.