An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.
Atomization of hydrides and their methylated analogues in a dielectric barrier discharge (DBD) plasma atomizer was investigated. Selected ion flow tube mass spectrometry (SIFT-MS) was chosen as a detector being capable of selective detection of non-atomized original volatile species allowing thus direct quantification of atomization efficiency. Selenium hydride (SeH2) and three volatile arsenic species, namely arsenic hydride (AsH3), monomethylarsane (CH3AsH2) and dimethylarsane ((CH3)2AsH), were selected as model analytes. The mechanistic study performed contributes to understanding of the atomization processes in atomic absorption spectrometry (AAS). The presented results are compatible with a complete atomization of arsenic hydride as well as its methylated analogues and with atomization efficiency of SeH2 below 80%. Using AsH3 as a model analyte and a combination of AAS and SIFT-MS detectors has revealed that the hydride is not atomized, but decomposed in the DBD atomizer in absence of hydrogen fraction in the carrier gas. Apart from investigation of analyte atomization, the SIFT-MS detector is capable of quantitative determination of water vapor content being either transported to, or produced in the atomizer. This information is crucial especially in the case of the low-power/temperature DBD atomizer since its performance is sensitive to the amount of water vapor introduced into the plasma.
- MeSH
- Arsenic * MeSH
- Mass Spectrometry MeSH
- Nebulizers and Vaporizers MeSH
- Spectrophotometry, Atomic MeSH
- Hydrogen MeSH
- Publication type
- Journal Article MeSH
The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.
- MeSH
- Breath Tests methods MeSH
- Adult MeSH
- Mass Spectrometry methods MeSH
- Ions MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Volatile Organic Compounds analysis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Volatile breath metabolites serve as potential disease biomarkers. Online mass spectrometry (MS) presents real-time quantification of breath volatile organic compounds (VOCs). The study aims to assess the relationship between two online analytical mass spectrometry techniques in the quantification of target breath metabolites: selected ion flow tube mass spectrometry (SIFT-MS) and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). The two following techniques were employed: (i) direct injection with bag sampling using SIFT-MS and PTR-ToF-MS and (ii) direct injection and thermal desorption (TD) tube comparison using PTR-ToF-MS. The concentration of abundant breath metabolites, acetone and isoprene, demonstrated a strong positive linear correlation between both mass spectrometry techniques (r = 0.97, r = 0.89, respectively; p < 0.001) and between direct injection and TD tube (r = 0.97, r = 0.92, respectively; p < 0.001) breath sampling techniques. This was reflected for the majority of short chain fatty acids and alcohols tested (r > 0.80, p < 0.001). Analyte concentrations were notably higher with the direct injection of a sampling bag compared to the TD method. All metabolites produced a high degree of agreement in the detection range of VOCs between SIFT-MS and PTR-ToF-MS, with the majority of compounds falling within 95% of the limits of agreement with Bland-Altman analysis. The cross platform analysis of exhaled breath demonstrates strong positive correlation coefficients, linear regression, and agreement in target metabolite detection rates between both breath sampling techniques. The study demonstrates the transferability of using data outputs between SIFT-MS and PTR-ToF-MS. It supports the implementation of a TD platform in multi-site studies for breath biomarker research in order to facilitate sample transport between clinics and the laboratory.
- MeSH
- Acetone analysis MeSH
- Butadienes analysis MeSH
- Breath Tests instrumentation methods MeSH
- Adult MeSH
- Hemiterpenes analysis MeSH
- Mass Spectrometry instrumentation methods MeSH
- Humans MeSH
- Volatile Organic Compounds analysis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
RATIONALE: The volatile compounds generated by the electrochemical reduction of atmospheric carbon dioxide and nitrogen include isobaric methanol (CH3 OH) and, potentially, hydrazine (N2 H4 ). To achieve quantification of hydrazine molecules by selected ion flow tube mass spectrometry (SIFT-MS), its reactions with H3 O+ , NO+ and O2+ reagent ions must be understood. METHODS: A SIFT study (using a SIFT-MS instrument) was carried out to obtain rate coefficients and product ions for the reactions of H3 O+ , NO+ and O2+ reagent ions with N2 H4 and CH3 OH molecules present in the humid headspace of their aqueous solutions. Using the kinetics data obtained, solution headspace concentrations were determined for both compounds as a function of their liquid-phase concentrations at 10, 20 and 35°C. RESULTS: Both compounds react with H3 O+ ions via rapid proton transfer to produce CH3 OH2+ and H5 N2+ ions with the common m/z value of 33. It is revealed that NO+ rapidly transfers charge to N2 H4 (rate coefficient k = 2.3 × 10-9 cm3 s-1 ) but only slowly associates with CH3 OH (k2eff = 7.1 × 10-11 cm3 s-1 ). Thus, selective analysis can be achieved using both H3 O+ and NO+ reagent ions. The headspace methanol vapour concentration was found to increase with increasing solution temperature, but that of hydrazine decreased with an associated increase of ammonia (NH3 ) as measured with O2+ reagent ions. CONCLUSIONS: The isobaric compounds methanol and hydrazine can be separately analysed in real time by SIFT-MS using H3 O+ and NO+ reagent ions, even when they co-occur in humid air. The evolution of hydrazine from aqueous solutions can be quantitatively monitored together with its decomposition at elevated temperatures.
- Publication type
- Journal Article MeSH
A new time-integrated thermal desorption technique has been developed that can be used with selected ion flow tube mass spectrometry, TI-TD/SIFT-MS, for off-line quantitative analyses of VOCs accumulated onto sorbents. Using a slow desorption temperature ramp, the absolute amounts of desorbed compounds can be quantified in real time by SIFT-MS and constitutional isomers can be separated. To facilitate application of this technique to environmental atmospheric monitoring, method parameters were optimised for quantification of the three common atmospheric monoterpenes: β-pinene, R-limonene and 3-carene. Three sorbent types, Tenax TA, Tenax GR and Porapak Q, were tested under 26 different desorption conditions determined by the "design of experiment", DOE, systematic approach. The optimal combination of type of sorbent, bed length, sampling flow rate, sample volume and the initial desorption temperature was determined from the experimental results by ANOVA. It was found that Porapak Q exhibited better efficiency of sample collection and further extraction for total monoterpene concentration measurements. On the other hand, Tenax GR or TA enabled separation of all three monoterpenes. The results of this laboratory study were tested with the sample accumulated from a branch of a Pinus nigra tree. Graphical abstract.
- Publication type
- Journal Article MeSH
RATIONALE: The major objective of this exploratory study was to implement selected ion flow tube mass spectrometry, SIFT-MS, as a method for the on-line quantification of the volatile organic compounds, VOCs, in the headspace of the ground roasted coffee. METHODS: The optimal precursor ions and characteristic analyte ions were selected for real-time SIFT-MS quantification of those VOCs that are the most abundant in the headspace or known to contribute to aroma. NO+ reagent ion reactions were exploited for most of the VOC analyses. VOC identifications were confirmed using gas chromatography/mass spectrometry, GC/MS, coupled with solid-phase microextraction, SPME. RESULTS: Thirty-one VOCs were quantified, including several alcohols, aldehydes, ketones, carboxylic acids, esters and some heterocyclic compounds. Variations in the concentrations of each VOC in the seven regional coffees were typically less than a factor of 2, yet concentrations patterns characteristic of the different regional coffees were revealed by heat map and principal component analyses. The coefficient of variation in the concentrations across the seven coffees was typically below 24% except for furfural, furan, methylfuran and guaiacol. CONCLUSIONS: The SIFT-MS analytical method can be used to quantify in real time the most important odoriferous VOCs in ground coffee headspace to sufficient precision to reveal some differences in concentration patterns for coffee produced in different countries.
- MeSH
- Aldehydes analysis MeSH
- Alcohols analysis MeSH
- Principal Component Analysis MeSH
- Food Analysis methods MeSH
- Coffea chemistry MeSH
- Mass Spectrometry methods MeSH
- Coffee chemistry MeSH
- Ketones analysis MeSH
- Food Handling MeSH
- Solid Phase Microextraction methods MeSH
- Gas Chromatography-Mass Spectrometry methods MeSH
- Volatile Organic Compounds analysis chemistry MeSH
- Publication type
- Journal Article MeSH
Much effort continues to be devoted to the development of devices to analyse breath ammonia with the anticipation that breath ammonia analyses will be useful in clinical practice. In this perspective we refer to the analytical techniques that have been used to measure breath ammonia, focusing on selected ion flow tube mass spectrometry, SIFT-MS, of which we have special knowledge and understanding. From the collected data obtained using the different techniques, we exam the origins of mouth- and nose-exhaled ammonia and conclude that mouth-exhaled ammonia is always elevated above a concentration that would be equilibrated with blood ammonia and is largely produced by the action of enzymes on salivary urea. Support to this conclusion is given by the reasonable correlation between blood urea concentration and mouth-exhaled ammonia concentration. Further, it is discussed that nose-exhaled ammonia largely originates at the alveolar interface and so its concentration more closely relates to the expected alveolar blood ammonia concentration. Ingestion of proteins results in increased blood/saliva urea and ultimately mouth-exhaled ammonia as does the generation of urease by H. pylori infection. It is also concluded that when mouth-exhaled ammonia is elevated then it may be due to either abnormally high blood urea, a high pH of the saliva/mouth/airways mucosa, poor oral hygiene or a combinations of these.
- MeSH
- Ammonia analysis MeSH
- Breath Tests methods MeSH
- Physiology * MeSH
- Medicine * MeSH
- Humans MeSH
- Mouth chemistry MeSH
- Exhalation MeSH
- Procedures and Techniques Utilization * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
A study has been carried out on the volatile organic compounds (VOCs) in the exhaled breath of patients suffering from inflammatory bowel disease (IBD), comprising 136 with Crohn's disease (CD) and 51 with ulcerative colitis (UC), together with a cohort of 14 healthy persons as controls. Breath samples were collected by requesting the patients to inflate Nalophan bags, which were then quantitatively analysed using selected ion flow tube mass spectrometry (SIFT-MS). Initially, the focus was on n-pentane that had previously been quantified in single exhalations on-line to SIFT-MS for smaller cohorts of IBD patients. It was seen that the median concentration of pentane was elevated in the bag breath samples of the IBD patients compared to those of the healthy controls, in accordance with the previous study. However, the absolute median pentane concentrations in the bag samples were about a factor of two lower than those in the directly analysed single exhalations-a good illustration of the dilution of VOCs in the samples of breath collected into bags. Accounting for this dilution effect, the concentrations of the common breath VOCs, ethanol, propanol, acetone and isoprene, were largely as expected for healthy controls. The concentrations of the much less frequently measured hydrogen sulphide, acetic acid, propanoic acid and butanoic acid were seen to be more widely spread in the exhaled breath of the IBD patients compared to those for the healthy controls. The relative concentrations of pentane and these other VOCs weakly correlate with simple clinical activity indices. It is speculated that, potentially, hydrogen sulphide and these carboxylic acids could be exhaled breath biomarkers of intestinal bacterial overgrowth, which could assist therapeutic intervention and thus alleviate the symptoms of IBD.
- MeSH
- Biomarkers analysis MeSH
- Butadienes analysis MeSH
- Crohn Disease diagnosis MeSH
- Breath Tests methods MeSH
- Adult MeSH
- Hemiterpenes analysis MeSH
- Acetic Acid analysis MeSH
- Carboxylic Acids analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Steam analysis MeSH
- Pentanes analysis MeSH
- Aged MeSH
- Hydrogen Sulfide analysis MeSH
- Volatile Organic Compounds analysis MeSH
- Colitis, Ulcerative diagnosis MeSH
- Exhalation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
RATIONALE: Peroxidation of lipids in cellular membranes results in the release of volatile organic compounds (VOCs), including saturated aldehydes. The real-time quantification of trace VOCs produced by cancer cells during peroxidative stress presents a new challenge to non-invasive clinical diagnostics, which as described here, we have met with some success. METHODS: A combination of selected ion flow tube mass spectrometry (SIFT-MS), a technique that allows rapid, reliable quantification of VOCs in humid air and liquid headspace, and electrochemistry to generate reactive oxygen species (ROS) in vitro has been used. Thus, VOCs present in the headspace of CALU-1 cancer cell line cultures exposed to ROS have been monitored and quantified in real time using SIFT-MS. RESULTS: The CALU-1 lung cancer cells were cultured in 3D collagen to mimic in vivo tissue. Real-time SIFT-MS analyses focused on the volatile aldehydes: propanal, butanal, pentanal, hexanal, heptanal and malondialdehyde (propanedial), that are expected to be products of cellular membrane peroxidation. All six aldehydes were identified in the culture headspace, each reaching peak concentrations during the time of exposure to ROS and eventually reducing as the reactants were depleted in the culture. Pentanal and hexanal were the most abundant, reaching concentrations of a few hundred parts-per-billion by volume, ppbv, in the culture headspace. CONCLUSIONS: The results of these experiments demonstrate that peroxidation of cancer cells in vitro can be monitored and evaluated by direct real-time analysis of the volatile aldehydes produced. The combination of adopted methodology potentially has value for the study of other types of VOCs that may be produced by cellular damage.
- MeSH
- Aldehydes analysis metabolism MeSH
- Cell Culture Techniques methods MeSH
- Electrochemical Techniques MeSH
- Mass Spectrometry methods MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasms metabolism MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
