Patrik Španěl

A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS

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.

Progress in SIFT-MS: Breath analysis and other applications

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

SIFT studies of the reactions of H3O+, NO+ and O2+ with a series of aldehydes and ketones

Abstract The results are reported of a selected ion flow tube (SIFT) study of the rate coefficients and the ionic products of the reactions of H3O+, NO+ and O2+ with some 11 aldehydes and nine ketones including the structural isomers of some. We assume that the 20 exothermic H3O+ proton transfer reactions proceed at the collisional rate and on this basis the large majority of the remaining 40 reactions included in this study also proceed close to the collisional rate. A variety of reaction processes are seen to occur. The H3O+ reactions proceed via proton transfer which for the ketones produces the protonated molecules only but which in the aldehyde reactions H2O elimination from the protonated molecule also occurs. The NO+ reactions with the aldehydes proceed largely via the process of hydride ion transfer whereas ion—molecule association is the dominant process in the NO+/ketone reactions with charge transfer also evident in some cases. The O2+ reactions with both the aldehydes and ketones proceed largely via charge transfer which in all reactions is partially dissociative producing several ionic products for the more polyatomic reactant molecules. Different products are observed in the reactions of O2+ with some of the structural isomers.

Analysis of formaldehyde in the headspace of urine from bladder and prostate cancer patients using selected ion flow tube mass spectrometry.

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.

Selected ion flow tube studies of the reactions of H3O+, NO+, and O2+ with several aromatic and aliphatic hydrocarbons

Abstract We describe the results of a selected ion flow tube study of the reactions of H 3 O + , NO + , and O 2 + with the 10 aromatic hydrocarbons benzene, toluene, 1,2-, 1,3-, and 1,4-dimethylbenzene, ethylbenzene, propylbenzene, 1,2,3-, 1,2,4-, and 1,3,5-trimethylbenzene, and 11 aliphatic hydrocarbons which are the alkanes n -butane and 2-methyl propane, n -pentane and 2-methyl butane, n -hexane, n -octane, n -decane and n -dodecane, the alkenes 1-pentene and 2-methyl-2-butene, and the dialkene 2-methyl butadiene (isoprene). All 30 reactions of the aromatic hydrocarbons are fast, the rate coefficients k being close to their respective collisional rate coefficients k c . The H 3 O + reactions all proceed by proton transfer producing the protonated parent molecules MH + , the NO + reactions proceed largely via nondissociative charge transfer producing M + ions, and the O 2 + reactions proceed via charge transfer which is partially dissociative in most cases producing M + and (M–CH 3 )+ ions. The k for the 33 aliphatic hydrocarbon reactions are much more varied, ranging from the immeasurable to k c . Proton transfer is endothermic in the reactions of H 3 O + with the smaller hydrocarbons whilst for the larger hydrocarbons reactions ion–molecule association occurs producing H 3 O + .M ions. The NO + reactions proceed largely via hydride ion transfer producing (M–H) + ions, although partial incorporation of the NO + into the larger hydrocarbons with subsequent fragmentation occurs producing minority ions like RHNO + (where R are radicals like C 3 H 7 , C 4 H 9 , etc). The O 2 + reactions all proceed by rapid dissociative charge transfer, the number of fragment ions increasing with the atomicity of the aliphatic hydrocarbon.

Analysis of breath, exhaled via the mouth and nose, and the air in the oral cavity

Analyses have been performed, using on-line selected ion flow tube mass spectrometry (SIFT-MS), of the breath of three healthy volunteers, as exhaled via the mouth and the nose and also of the air in the oral cavity during breath hold, each morning over a period of one month. Nine trace compounds have been quantified and concentration distributions have been constructed. Of these compounds, the levels of acetone, methanol and isoprene are the same in the mouth-exhaled and the nose-exhaled breath; hence, we deduce that these compounds are totally systemic. The levels of ammonia, ethanol and hydrogen cyanide are much lower in the nose-exhaled breath than in the mouth-exhaled breath and highest in the oral cavity, indicating that these compounds are largely generated in the mouth with little being released at the alveolar interface. Using the same ideas, both the low levels of propanol and acetaldehyde in mouth-exhaled breath appear to have both oral and systemic components. Formaldehyde is at levels in mouth- and nose-exhaled breath and the oral cavity that are lower than that of the ambient air and so its origin is difficult to ascertain, but it appears to be partially systemic. These results indicate that serious contamination of alveolar breath exhaled via the mouth can occur and if breath analysis is to be used to diagnose metabolic disease then analyses should be carried out of both mouth- and nose-exhaled breath to identify the major sources of particular trace compounds.

Application of ion chemistry and the SIFT technique to the quantitative analysis of trace gases in air and on breath

Abstract Our major objective in this paper is to describe a new method we have developed for the analysis of trace gases at partial pressures down to the ppb level in atmospheric air, with special emphasis on the detection and quantification of trace gases on human breath. It involves the use of our selected ion flow tube (Sift) technique which we previously developed and used extensively for the study of gas phase ionic reactions occurring in ionized media such as the terrestrial atmosphere and interstellar gas clouds. Before discussing this analytical technique we describe the results of our very recent Sift and flowing afterglow (FA) studies of the reactions of the H3O+ and OH− ions, of their hydrates H3O+(H2O)1,2,3 and OH− (H2O)1,2, and of NO+ and O2 +, with several hydrocarbons and oxygen-bearing organic molecules, studies that are very relevant to our trace gas analytical studies. Then follows a detailed discussion of the application of our Sift technique to trace gas analysis, after which we presen...

Selected ion flow tube – mass spectrometry: detection and real‐time monitoring of flavours released by food products

This paper is concerned with the application of our selected ion flow tube mass spectrometric analytical method (SIFT-MS) to the analysis of the complex aromas of some food products. This SIFT/MS chemical ionisation technique, to date mostly applied to breath analysis in medicine and health and safety practice, involves the use of pre-selected H3O+, NO+ and O2+ ions to ‘soft ionise’ the volatile organic compounds (VOCs) that constitute complex mixtures such as food aromas. The kinetics involved are well-defined thus allowing quantification of several trace gases simultaneously in an air sample in real time without the need for pre-calibration. In order to facilitate the interpretation of the spectra obtained for complex mixtures by SIFT/MS we have carried out detailed studies of the reactions of these three ion species with a wide variety of organic compounds including many alcohols, aldehydes, ketone, esters and organosulphur compounds. A large kinetics database has thus been created and general patterns of reactivity are seen which are shown to be invaluable for SIFT/MS analyses. Thus, the SIFT mass spectra for some specific food flavours and for the VOCs emitted by cut onion, crushed garlic and ripe banana are presented and interpreted. Finally, the temporal variations in the concentrations of some of the VOCs emitted by these food products, obtained in real time using SIFT/MS in the selected ion monitoring mode, are also presented, which demonstrate the value of this analytical technique in food research. Copyright

Compounds enhanced in a mass spectrometric profile of smokers' exhaled breath versus non-smokers as determined in a pilot study using PTR-MS

A pilot study has been carried out to define typical characteristics of the trace gas compounds in exhaled breath of non-smokers and smokers to assist interpretation of breath analysis data from patients who smoke with respiratory diseases and lung cancer. Exhaled breath was analyzed using proton transfer reaction-mass spectrometry (PTR-MS) for 370 volunteers (81 smokers, 210 non-smokers, 79 ex-smokers). Volatile organic compounds corresponding to product ions at seven mass-to-charge ratios (m/z 28, 42, 69, 79, 93, 97, 123) in the PTR-MS spectra differentiated between smokers and non-smokers. The Youden index (= maximum of sensitivity + specificity - 1, YI) as a measure for differentiation between smokers and non-smokers was YI = 0.43 for ions at the m/z values 28 (tentatively identified as HCN), YI = 0.75 for m/z = 42 (tentatively identified as acetonitrile) and YI = 0.53 for m/z = 79 (tentatively identified as benzene). No statistically significant difference between smokers and non-smokers was observed for the product ions at m/z = 31 and 33 (compounds tentatively identified as formaldehyde and methanol). When interpreting the exhaled breath of lung cancer or COPD patients, who often smoke, compounds appearing at the above-mentioned seven mass-to-charge ratios should be considered with appropriate care to avoid misdiagnosis. Validation studies in larger numbers of patients with more precise delineation of their smoking behavior and using additional analytical techniques such as GC/MS and SIFT-MS should be carried out.

The challenge of breath analysis for clinical diagnosis and therapeutic monitoring

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.