Ion-molecule Reaction Mass Spectrometry Research Articles

Real-time determination of volatile organic compounds (VOCs) by ion molecule reaction – mass spectrometry (IMR-MS)

Comprehensive analytical validation studies of a developed ion molecule reaction – mass spectrometer (IMR-MS) were undertaken for the real-time determination of volatile organic compounds (VOCs) in air. The instrument was developed with a focus on promoting chemical ionization (CI) in the reaction chamber by direct sample loading and enhancing maintenance efficiency and reliability of the results. Instrument stability was assessed through a system check and pre-performance check process, and consequently, the instrumental and analytical conditions including the plasma generation, pressure, temperature, and flow rate were successfully optimized. Relevant performance characteristics, such as mass resolution, mass detection range, accuracy, and precision were also investigated by VOC standards composed of benzene, toluene, perfluorotoluene, propylbenzene, and octane. To evaluate whether the performance of the technology is comparable to already accepted techniques, the quantitative results of the IMR-MS were compared with those of a commercial mass spectrometer. This evaluation was successful and suggests the applicability of the technology for spillage accidents of hazardous chemicals and identification of odor-causing substances as well as for real-time gas analysis.

Perovskite Catalyst for In-Cylinder Coating to Reduce Raw Pollutant Emissions of Internal Combustion Engines.

Aiming to achieve the highest combustion efficiency and less pollutant emission, a catalytic coating for cylinder walls in internal combustion engines was developed and tested under several conditions. The coating consists of a La0.8Sr0.2CoO3 (LSCO) catalyst on an aluminum-based ceramic support. Atomic force microscopy was applied to investigate the surface roughness of the LSCO coating, while in situ diffuse infrared Fourier transform spectroscopy was used to obtain the molecular understanding of adsorption and conversion. In addition, the influence of LSCO-coated substrates on the flame quenching distance was studied in a constant-volume combustion chamber. Investigations conclude that an LSCO coating leads to a reduction of flame quenching at low wall temperatures but a negligible effect at high temperatures. Finally, the influence of LSCO coatings on the in-cylinder wall-near gas composition was investigated using a fast gas sampling methodology with sample durations below 1 ms. Ion molecule reaction mass spectrometry and Fourier transform infrared spectroscopy revealed a significant reduction of hydrocarbons and carbon monoxide when LSCO coating was applied.

On-Line Composition Analysis of Complex Hydrocarbon Streams by Time-Resolved Fourier Transform Infrared Spectroscopy and Ion-Molecule Reaction Mass Spectrometry.

On-line composition analysis of complex hydrocarbon mixtures is highly desirable to determine the composition of process streams and to study chemical reactions in heterogeneous catalysis. Here, we show how the combination of time-resolved Fourier transform infrared spectroscopy and ion–molecule-reaction mass spectrometry (IMR-MS) can be used for compositional analysis of processed plant biomass streams. The method is based on the biomass-derived model compound 2,5-dimethylfuran and its potential catalytic conversion to valuable green aromatics, for example, benzene, toluene, and xylenes (BTX) over zeolite β. Numerous conversion products can be determined and quantified simultaneously in a temporal resolution of 4 min–1 without separation of individual compounds. The realization of this method enables us to study activity, selectivity, and changes in composition under transient reaction conditions. For example, increasing isomerization of 2,5-dimethylfuran to 2,4-dimethylfuran, 2-methyl-2-cyclopenten-1-one, and 2-methyl-2-cyclopenten-1-one is observed as the catalyst is exposed to the reactant, while BTX and olefin formation is decreasing.

Exhaled Breath and Oxygenator Sweep Gas Propionaldehyde in Acute Respiratory Distress Syndrome

Background: Oxidative stress-induced lipid peroxidation (LPO) due to neutrophil-derived reactive oxygen species plays a key role in the early stage of the acute respiratory distress syndrome (ARDS). Monitoring of oxidative stress in this patient population is of great interest, and, ideally, this can be done noninvasively. Recently, propionaldehyde, a volatile chemical compound (VOC) released during LPO, was identified in the breath of lung transplant recipients as a marker of oxidative stress. The aim of the present study was to identify if markers of oxidative stress appear in the oxygenator outflow gas of patients with severe ARDS treated with veno-venous extracorporeal membrane oxygenation (ECMO). Methods: The present study included patients with severe ARDS treated with veno-venous ECMO. Concentrations of acetone, isoprene, and propionaldehyde were measured in inspiratory air, exhaled breath, and oxygenator inflow and outflow gas at corresponding time points. Ion-molecule reaction mass spectrometry was used to measure VOCs in a sequential order within the first 24 h and on day three after ECMO initiation. Results: Nine patients (5 female, 4 male; age = 42.1 ± 12.2 year) with ARDS and already established ECMO therapy (pre-ECMO PaO2/FiO2 = 44.0 ± 11.5 mmHg) were included into analysis. VOCs appeared in comparable amounts in breath and oxygenator outflow gas (acetone: 838 (422–7632) vs. 1114 (501–4916) ppbv; isoprene: 53.7 (19.5–244) vs. 48.7 (37.9–108) ppbv; propionaldehyde: 53.7 (32.1–82.2) vs. 42.9 (24.8–122) ppbv). Concentrations of acetone, isoprene, and propionaldehyde in breath and oxygenator outflow gas showed a parallel course with time. Conclusions: Acetone, isoprene, and propionaldehyde appear in breath and oxygenator outflow gas in comparable amounts. This allows for the measurement of these VOCs in a critically ill patient population via the ECMO oxygenator outflow gas without the need of ventilator circuit manipulation.

Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

BackgroundIn the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease.MethodsThe concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated.ResultsThe final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model.ConclusionsPancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity.

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry.

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds’ (VOCs) pattern when compared to controls. Patients 10–17 years of age, were divided into four groups: Crohn’s disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non–invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.

Exhaled breath volatile organic and inorganic compound composition in end-stage renal disease.

Patients with end-stage renal disease (ESRD) are characterized by uremia and increased oxidative stress. The aim of this study was to investigate the influence of hemodialysis on breath ammonia and volatile oxidative stress parameters. Breath analysis was performed in 18 ESRD patients prior, during, and 30minutes after a hemodialysis session. Parameters of hemodialysis efficiency and oxidative stress (lipid peroxides, total antioxidative capacity, myeloperoxidase, and malondialdehyde) were measured in blood at the beginning, after 30minutes, and at the end of the dialysis session. 11 healthy volunteers with normal renal function served as a control group. Ion-molecule reaction mass spectrometry was used for breath-gas analysis. Initial elevated concentrations of breath ammonia decreased during hemodialysis and correlated with serum urea levels (r2=0.74), whereas isoprene concentrations increased. Breath concentrations of malondialdehyde and pentane (MDA-P) were significantly elevated in ESRD patients (p <0.01). Within the blood, a significant decrease of malondialdehyde was notable during hemodialysis treatment, whereas levels of lipid peroxides and myeloperoxidase increased. Exhaled breath of patients with ESRD on regular hemodialysis treatment is characterized by an increase in ammonia and MDA-P. The efficient decrease of breath ammonia and its close correlation to serum urea during hemodialysis suggests its possible use as a noninvasive marker to monitor dialysis efficacy.

On line engine oil consumption monitoring via the gaseous total sulfur signal SO2 in the raw exhaust of the engine utilizing the sensitive ion molecule reaction mass spectrometry

The dynamic monitoring of oil consumption in IC engines is approached with various techniques ranging from radioactive counting to detection of halogenated tracer compounds or polyaromatic hydrocarbon tracers, to monitoring unburned hydrocarbons as residues from engine oil. This article discusses the method of gaseous SO2 measurement in raw exhaust its benefits and limitations of todays status. Modern engines consume about 2 to 5 g/h of engine oil under low and medium load but consumption may go up to 130 g/h in negative load conditions. Particulate filters must be desulfated every 5000 km even when sulfur free fuel is in use. For the oil measurement in the raw exhaust all possible Sulfur compounds are converted to SO2 in a hot oxidizing atmosphere. Additional pure oxygen in the form of ozone is added to the oxidizer for very low lambda engine conditions and the conversion of sulfur on particulates into SO2. A sensitive mass spectrometer operating in an ion molecule ionization mode measures gaseous SO2 from concentrations of 0.02 ppm to 50 ppm in measurement cycles from 2 Hz to 0.2 Hz depending on if long term measurement or dynamic operation is chosen. Technical description of pressure reduction, gas transfer, oxidation efficiencies and lower detection levels of the instrumentation are given as well as data on a complete engine map and data on reproducibility of the SO2 method are presented.

Monitoring variations of dimethyl sulfide and dimethylsulfoniopropionate in seawater and the atmosphere based on sequential vapor generation and ion molecule reaction mass spectrometry.

To monitor the fluctuations of dimethyl sulfur compounds at the seawater/atmosphere interface, an automated system was developed based on sequential injection analysis coupled with vapor generation-ion molecule reaction mass spectrometry (SIA-VG-IMRMS). Using this analytical system, dissolved dimethyl sulfide (DMS(aq)) and dimethylsulfoniopropionate (DMSP), a precursor to DMS in seawater, were monitored together sequentially with atmospheric dimethyl sulfide (DMS(g)). A shift from the equilibrium point between DMS(aq) and DMS(g) results in the emission of DMS to the atmosphere. Atmospheric DMS emitted from seawater plays an important role as a source of cloud condensation nuclei, which influences the oceanic climate. Water samples were taken periodically and dissolved DMS(aq) was vaporized for analysis by IMRMS. After that, DMSP was hydrolyzed to DMS and acrylic acid, and analyzed in the same manner as DMS(aq). The vaporization behavior and hydrolysis of DMSP to DMS were investigated to optimize these conditions. Frequent (every 30 min) determination of the three components, DMS(aq)/DMSP (nanomolar) and DMS(g) (ppbv), was carried out by SIA-VG-IMRMS. Field analysis of the dimethyl sulfur compounds was undertaken at a coastal station, which succeeded in showing detailed variations of the compounds in a natural setting. Observed concentrations of the dimethyl sulfur compounds both in the atmosphere and seawater largely changed with time and similar variations were repeatedly observed over several days, suggesting diurnal variations in the DMS flux at the seawater/atmosphere interface.

Quantification of propionaldehyde in breath of patients after lung transplantation

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia–reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart–lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde were performed in seven patients after lung (n=5) or heart–lung (n=2) transplantation, ventilated patients (n=12), and healthy volunteers (n=17) using online ion-molecule reaction mass spectrometry. Increased concentrations of acetone (transplanted: 3812 [2347–12498]; ventilated: 1255 [276–1959]; healthy: 631 [520–784] ppbv; P<.001) and propionaldehyde (transplanted: 270 [70–424]; ventilated: 82 [41.8–142]; healthy: 1.7 [0.1–11.8] ppbv; P<.001) were found in expiratory air of transplanted and ventilated patients. Propionaldehyde resulting from spontaneous fragmentation of peroxides due to free radical-induced LPO after I/R injury in patients after lung or heart–lung transplantation can be quantified in expired breath.

Monitoring of Bacterial Growth and Rapid Evaluation of Antibiotic Susceptibility by Headspace Gas Analysis

Testing of antibiotic resistance by conventional microbiological techniques can be very time-consuming. Measuring the release of volatile organic compounds (VOCs) in the headspace of bacterial culture using mass spectrometry or other gas sensing principles might provide a novel approach in detection of antibiotic susceptibility. In the present study VOCs produced by different strains of Escherichia coli and Staphylococcus aureus were monitored by Ion-molecule Reaction-Mass Spectrometry (IMR-MS). Methanethiol was identified as a marker for bacterial growth. Subsequently, various metal-oxide gas sensors were screened for sensitivity to methanethiol in order to select appropriate cost-efficient sensors for future application in clinical routine.

Minimal retarded Propofol signals in human breath using ion mobility spectrometry

Propofol is a short-acting, intravenously administered hypnotic agent. Since the introduction of propofol into clinical practice, it has become the intravenous induction agent of choice for anaesthesia providers (Fig. 1). The physicochemical properties of Propofol are given in Table 1. Currently, there are no simple, reliable and clinically useful measures available to quantify Propofol in humans at the bedside. For investigations in pharmacokinetics and dynamics Propofol is measured in serum samples, which are invasive, time-consuming and therefore results are not directly available. The level of Propofol in the exhaled air can potentially be used as an indicator of patients’ hypnotic depth and would provide the possibility to measure the Propofol concentration on-line. Generally, several methods are under investigation to monitor the concentration of Propofol in exhaled breath. For example, mass spectrometry with emphasis on proton transfer reaction mass spectrometry, ion-molecule reaction mass spectrometry or GC/MS have been described [1–7]. The detection of Propofol in exhaled air using ion mobility spectrometry coupled to multi-capillary (MCC) columns was shown most recently [8–11]. The MCC provides the possibility to work within humid environment. The reactant ion peak (RIP) is clearly separated from the peak of Propofol using MCC combined with an IMS. The identification uses the drift time of the ions formed from Propofol and the retention time within the MCC. The signal intensity can be related to the concentration range with relevance for clinical diagnostics[8] . Further details with respect to the advantages and disadvantages of MCC [12–17] and the IMS [18–25] are well known. With respect to the detection of Propofol, a retention time of about 10 min was realized keeping the MCC adjusted at 40 °C. Perl et al. [9] estimated, that at higher MCC temperatures, retention times in the range of 1 min could be achieved. Zhou et al. [26] used a membrane inlet system for on-line measurement of Propofol in an anesthetized mouse and showed direct Propofol concentration in a time series. In their mouse model, the time profile showed a gap of about 10 min before the Propofol signal was observable. A close relation to serum Propofol concentration in air was found using mass spectrometric methods [4, 7]. Recently, a strong correlation between the serum Propofol concentration and signal intensity of ion mobility spectrometry has also been shown [8, 9, 11]. The goal of the present pilot is to show that by modifying the MCC/IMS peak of Propofol values can be obtained online within 60 s. To demonstrate biologically meaningful variations the MCC/IMS was applied in a conventional operation room. The peak intensities delivered by BioScout could then directly be correlated to the BIS-values of brain activity, where Propofol is expected to have its major effects in vivo.

Breath isoprene concentrations in persons undergoing general anesthesia and in healthy volunteers

Human breath contains an abundance of volatile organic compounds (VOCs). Analysis of breath VOC may be used for diagnosis of various diseases or for on-line monitoring in anesthesia and intensive care. However, VOC concentrations largely depend on the breath sampling method and have a large inter-individual variability. For the development of breath tests, the influence of breath sampling methods and study subject characteristics on VOC concentrations has to be known. Therefore, we investigated the VOC isoprene in 62 study subjects during anesthesia and 16 spontaneously breathing healthy volunteers to determine (a) the influence of artificial and spontaneous ventilation and (b) the influence of study subject characteristics on breath isoprene concentrations. We used ion molecule reaction mass spectrometry for high-resolution breath-by-breath analysis of isoprene. We found that persons during anesthesia had significantly increased inspiratory and end-expiratory isoprene breath concentrations. Measured isoprene concentrations (median [first quartile–third quartile]) were in the anesthesia group: 54 [40–79] ppb (inspiratory) and 224 [171–309] ppb (end-expiratory), volunteer group: 14 [11–17] ppb (inspiratory) and 174 [124–202] ppb (end-expiratory). Higher end-tidal CO2 concentrations in ventilated subjects were associated with higher expiratory isoprene levels. Furthermore, inspiratory and end-expiratory isoprene concentrations were correlated during anesthesia (r = 0.603, p < 0.001). Multivariate analysis showed that men had significantly higher end-expiratory isoprene concentrations than women. Rebreathing of isoprene from the anesthesia machine possibly accounts for the observed increase in isoprene in the anesthesia group.

A New Method to Detect Pancreatic Ductal Adenocarcinoma by Analysis of Volatile Organic Compounds (VOCs) in Alveolar Air

Context Early diagnosis of pancreatic ductal adenocarcinoma (PDA) is still a challenge. In the last decade many studies showed that the air exhaled by subjects suffering from lung and breast tumor shows peculiar profiles of volatile organic compounds (VOCs). The possible causal factors of PDA are able to alter the concentration of some VOCs in the alveolar air which can be collected with an easy-to-use, cheap and reliable device. Objective To determine a VOCs profile in the alveolar air able to discriminate patients suffering from PDA. Methods Air samples were obtained from patients affected by PDA cyto-histologically confirmed admitted in the Surgical Unit B of Verona University Hospital (Study Group). Patients characteristics, clinical and biohumoral data, surgical procedures and histological specimen reports were prospectively collected. The same air samples were collected from healthy subjects (Control Group) and in the environmental air of the rooms where the subjects studied were staying. Air samples were analysed by an ion molecule reaction-mass spectrometry analysis (IMR-MS). Through principal components analysis and multivariate logistic regression, a predictive model was created to distinguish subjects with PDA from control subjects. Results The concentration of 92 compounds among VOCs and gases (CO 2 and O 2 included) was measured in 75 patients end-tidal breath and in 144 control subjects. The predictive model was built on 65 cases and 102 controls with ages between 40 and 75 years and was based on 10 VOCs significantly and independently associated with the outcome, showing sensitivity and specificity values of 98.67% and 95.10%, respectively and an area under the ROC curve of 0.9887. Conclusion Using a profile of some VOCs we identify an algorithm able to discriminate subjects with pancreatic adenocarcinoma from control subjects with the best sensitivity and specificity ever reported by a single test. The test is cheap, non invasive and reproducible. We believe that it could be applied extensively and it could represent a screening test in high risk population for pancreatic ductal adenocarcinoma.

Volatile compound profiling for the identification of Gram-negative bacteria by ion-molecule reaction-mass spectrometry

Fast and reliable methods for the early detection and identification of micro-organism are of high interest. In addition to established methods, direct mass spectrometry-based analysis of volatile compounds (VCs) emitted by micro-organisms has recently been shown to allow species differentiation. Thus, a large number of pathogenic Gram-negative bacteria, which comprised Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris and Serratia marcescens, were subjected to headspace VC composition analysis using direct mass spectrometry in a low sample volume that allows for automation. Ion-molecule reaction-mass spectrometry (IMR-MS) was applied to headspace analysis of the above bacterial samples incubated at 37°C starting with 10(2) CFU ml(-1) . Measurements of sample VC composition were performed at 4, 8 and 24 h. Microbial growth was detected in all samples after 8 h. After 24 h, species-specific mass spectra were obtained allowing differentiation between bacterial species. IMR-MS provided rapid growth detection and identification of micro-organisms using a cumulative end-point model with a short analysis time of 3 min per sample. Following further validation, the presented method of bacterial sample headspace VC analysis has the potential to be used for bacteria differentiation.

Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation

Approximately 50 % of all clinically proven infections in critically ill patients are caused by Gram-positive bacteria. The timely and appropriate treatment of these infections is vital in order to avoid negative outcomes. Hence, fast and reliable methods are needed for the early detection and identification of microorganisms. Recently, direct mass spectrometry-based analysis of volatile organic compounds emitted by microorganisms has been employed to study Gram-negative bacteria. Here, we report a feasibility study of ion molecule reaction mass spectrometry (IMR-MS) for in vitro growth detection and species differentiation of selected Gram-positive bacteria that are frequently isolated in blood culture samples, namely, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis. Ion molecule reaction mass spectrometry was used to analyze the headspace above cultures containing Gram-positive bacteria incubated at 37 °C starting with 10(2) colony-forming units (CFU)/ml. Measurements to determine the presence of volatile organic compounds were performed 4, 8, and 24 h after incubation, respectively. The detection of microbial growth was accomplished already after 8 h in cultures containing E. faecalis. After 24 h of incubation, characteristic mass spectra were obtained for all species. Processing these mass spectra by hierarchic clustering and principal component analysis (PCA) enabled us to differentiate between bacterial species. IMR-MS in conjunction with a cumulative end-point model provides the means for rapid growth detection and differentiation of Gram-positive bacteria on the species level, typically within an analysis time of less than 3 min per sample.

Determination of hazardous volatile organic compounds in the Hoffmann list by ion‐molecule reaction mass spectrometry

Off-line gas or liquid chromatographic mass spectrometry techniques are the most widely used method for analysis of hazardous, carcinogenic volatile organic compounds (VOCs) in mainstream cigarette smoke. However, these conventional techniques can lead to modification of VOCs during sample preparation due to the high reactivity of VOCs. Thus, the development of on-line mass spectrometric methods for analysis of VOCs is desirable to circumvent this problem. The accurate identification of VOCs is a critical step in the analysis of cigarette smoke. Here, we use ion-molecule reaction mass spectrometry (IMR-MS) to study the behavior of standard VOCs in the Hoffmann list during this analytical procedure, and then to profile the VOCs in mainstream cigarette smoke using this on-line mass spectrometric method. We first discuss and summarize the charge transfer (CT) ionization and further fragmentation of 20 standard VOCs in the Hoffmann list with the ion reagents Hg(+), Xe(+), and Kr(+). The IMR-MS instrument was then connected to a Borgwaldt-RM20H rotary smoking machine in order to study VOCs in mainstream cigarette smoke on-line. Using this procedure, more than 20 VOCs were identified by IMR-MS by comparison with experimental results obtained on standard VOCs. The IMR-MS technique can potentially result in reduced molecular fragmentation during analysis of VOCs. However, significant fragmentation still occurs during IMR-MS when the ionization energy (IE) of the ion reagent is much higher than the IE of the VOC, given that excess energy is stored in the newly formed ion during CT ionization. Given that IMR-MS cannot distinguish between isobaric compounds or isomers, we summarize the possible overlapping mass peaks from these isobaric species that may be present in analyses of VOCs. Selection of the ion reagent for IMR-MS should be based on the need to ensure CT ionization of the analytes, as well as avoiding their severe fragmentation.

Time course of expiratory propofol after bolus injection as measured by ion molecule reaction mass spectrometry

Propofol in exhaled breath can be detected and monitored in real time by ion molecule reaction mass spectrometry (IMR-MS). In addition, propofol concentration in exhaled breath is tightly correlated with propofol concentration in plasma. Therefore, real-time monitoring of expiratory propofol could be useful for titrating intravenous anesthesia, but only if concentration changes in plasma can be determined in exhaled breath without significant delay. To evaluate the utility of IMR-MS during non-steady-state conditions, we measured the time course of both expiratory propofol concentration and the processed electroencephalography (EEG) as a surrogate outcome for propofol effect after an IV bolus induction of propofol. Twenty-one patients scheduled for routine surgery were observed after a bolus of 2.5 mg kg(-1) propofol for induction of anesthesia. Expiratory propofol was measured using IMR-MS and the cerebral propofol effect was estimated using the bispectral index (BIS). Primary endpoints were time to detection of expiratory propofol and time to onset of propofol's effect on BIS, and the secondary endpoint was time to peak effect (highest expiratory propofol or lowest BIS). Expiratory propofol and changes in BIS were first detected at 43 ± 21 and 49 ± 11 s after bolus injection, respectively (P = 0.29). Peak propofol concentrations (9.2 ± 2.4 parts-per-billion) and lowest BIS values (23 ± 4) were reached after 208 ± 57 and 219 ± 62 s, respectively (P = 0.57). Expiratory propofol concentrations measured by IMR-MS have similar times to detection and peak concentrations compared with propofol effect as measured by the processed EEG (BIS). This suggests that expiratory propofol concentrations may be useful for titrating intravenous anesthesia.

Trace analysis of small gas samples in sealed containers with mass spectrometry using static dilution

A sampling method for the analysis of small amounts of gases from sealed containers is described. Liquefied pressurised gas samples were expanded into a vacuum box and statically diluted with ultrapure nitrogen. The equations for the sample dilution were established, relating the measured impurity amount fractions in the sample mixture to their partial pressures in the sealed container and, in the case of oxygen, to the air pressure. Ion–molecule reaction mass spectrometry allowed identification and measurement of trace impurities corresponding to partial pressures in the range of 1 hPa in the container. The method was applied for determining the identity and amount of gaseous impurities in n-butane used in implantable gas pressure–operated drug infusion pumps. Impurities from the n-butane supply cylinder or from decomposition products, for example due to the laser welding of the Ti plugs of the containers, could be excluded by the results of saturation vapour pressure measurements, FID gas chromatograms and IMR mass spectra. The variability in pressure versus volume among tested infusion pump samples was associated with excess oxygen, attributable to an excessive residual air pressure in the gas containers before they were filled with n-butane. The sample preparation method is principally applicable to measure the composition of small amounts of gas mixtures and gaseous impurities with identified IMR mass spectra down to trace levels—even for ubiquitous substances like oxygen. The volume of the produced gas mixtures allows characterisation of the gas by standard gas analytical methods and for impurities by trace gas analytical methods.

Time course of ethanol and propofol exhalation after bolus injection using ion molecule reaction–mass spectrometry

The transit of ethanol from blood to breath gas is well characterised. It is used for intraoperative monitoring and in forensic investigations. A further substance, which can be measured in breath gas, is the phenol propofol. After a simultaneous bolus injection, the signals (time course and amplitude) of ethanol and propofol in breath gas were detected by ion molecule reaction-mass spectrometry (IMR-MS) and compared. After approval by the regional authorities, eight pigs were endotracheally intubated after a propofol-free induction with etomidate. Boluses of ethanol (16 μg/kg) and propofol (4 or 2 mg/kg) were infused alone and in combination. For both substances, breath gas concentrations were continuously measured by IMR-MS; the delay time, time to peak and amplitude were determined and compared using non-parametric statistic tests. IMR-MS allows a simultaneous continuous measurement of both substances in breath gas. Ethanol appeared (median delay time, 12 vs 29.5 s) and reached its peak concentration (median time to peak, 45.5 vs 112 s) significantly earlier than propofol. Time courses of ethanol and propofol in breath gas can be simultaneously described with IMR-MS. Differing pharmacological and physicochemical properties of the two substances can explain the earlier appearance and time to peak of ethanol in breath gas compared with propofol.