Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis, part 2

In a recent paper we presented a simple two compartment model which describes the influence of inhaled concentrations on exhaled breath concentrations for volatile organic compounds (VOCs) with small Henry constants. In this paper we extend this investigation concerning the influence of inhaled concentrations on exhaled breath concentrations for VOCs with higher Henry constants. To this end we extend our model with an additional compartment which takes into account the influence of the upper airways on exhaled breath VOC concentrations

A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds

Isothermal rebreathing has been proposed as an experimental technique for estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs) in exhaled breath. Using the prototypic test compound acetone we demonstrate that the end-tidal breath profiles of such substances during isothermal rebreathing show characteristics that contradict the conventional pulmonary inert gas elimination theory due to Farhi. On the other hand, these profiles can reliably be captured by virtue of a previously developed mathematical model for the general exhalation kinetics of highly soluble, blood-borne VOCs, which explicitly takes into account airway gas exchange as major determinant of the observable breath output. This model allows for a mechanistic analysis of various rebreathing protocols suggested in the literature. In particular, it clarifies the discrepancies between in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yields further quantitative insights into the physiological components of isothermal rebreathing.Comment: 21 page

Physiological modeling of isoprene dynamics in exhaled breath

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.Comment: 14 page

Modeling of breath methane concentration profiles during exercise on an ergometer

We develop a simple three compartment model based on mass balance equations which quantitatively describes the dynamics of breath methane concentration profiles during exercise on an ergometer. With the help of this model it is possible to estimate the endogenous production rate of methane in the large intestine by measuring breath gas concentrations of methane.Comment: 17 pages, 4 figure

Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags

The stability of 41 selected breath constituents in three types of polymer sampling bags, Tedlar, Kynar, and Flexfilm, was investigated using solid phase microextraction and gas chromatography mass spectrometry. The tested molecular species belong to different chemical classes (hydrocarbons, ketones, aldehydes, aromatics, sulphurs, esters, terpenes, etc.) and exhibit close-to-breath low ppb levels (3–12 ppb) with the exception of isoprene, acetone and acetonitrile (106 ppb, 760 ppb, 42 ppb respectively). Stability tests comprised the background emission of contaminants, recovery from dry samples, recovery from humid samples (RH 80% at 37 °C), influence of the bag’s filling degree, and reusability. Findings yield evidence of the superiority of Tedlar bags over remaining polymers in terms of background emission, species stability (up to 7 days for dry samples), and reusability. Recoveries of species under study suffered from the presence of high amounts of water (losses up to 10%). However, only heavier volatiles, with molecular masses higher than 90, exhibited more pronounced losses (20–40%). The sample size (the degree of bag filling) was found to be one of the most important factors affecting the sample integrity. To sum up, it is recommended to store breath samples in pre-conditioned Tedlar bags up to 6 hours at the maximum possible filling volume. Among the remaining films, Kynar can be considered as an alternative to Tedlar; however, higher losses of compounds should be expected even within the first hours of storage. Due to the high background emission Flexfilm is not suitable for sampling and storage of samples for analyses aiming at volatiles at a low ppb level

Monitoring of selected skin-borne volatile markers of entrapped humans by selective reagent ionization time of flight mass spectrometry in NO+ mode

[Image: see text] Selective reagent ionization time-of-flight mass spectrometry with NO(+) as the reagent ion (SRI-TOF-MS (NO(+))) was applied for near real-time monitoring of selected skin-borne constituents which are potential markers of human presence. The experimental protocol involved a group of 10 healthy volunteers enclosed in a body plethysmography chamber mimicking the entrapment environment. A total of 12 preselected omnipresent in human scent volatiles were quantitatively monitored. Among them there were six aldehydes (n-propanal, n-hexanal, n-heptanal, n-octanal, n-nonanal, and 2 methyl 2-propenal), four ketones (acetone, 2-butanone, 3-buten-2-one, and 6-methyl-5-hepten-2-one), one hydrocarbon (2-methyl 2-pentene), and one terpene (DL-limonene). The observed median emission rates ranged from 0.28 to 44.8 nmol × person(–1) × min(–1) (16–1530 fmol × cm(–2) × min(–1)). Within the compounds under study, ketones in general and acetone in particular exhibited the highest abundances. The findings of this study provide invaluable information about formation and evolution of a human-specific chemical fingerprint, which could be used for the early location of entrapped victims during urban search and rescue operations (USaR)

Product ion distributions for the reactions of NO+ with some physiologically significant volatile organosulfur and organoselenium compounds obtained using a selective reagent ionization time-of-flight mass spectrometer

RATIONALE: The reactions of NO(+) with volatile organic compounds (VOCs) in Selective Reagent Ionization Time-of-Flight Mass Spectrometry (SRI-TOF-MS) reactors are relatively poorly known, inhibiting their use for trace gas analysis. The rationale for this product ion distribution study was to identify the major product ions of the reactions of NO(+) ions with 13 organosulfur compounds and 2 organoselenium compounds in an SRI-TOF-MS instrument and thus to prepare the way for their analysis in exhaled breath, in skin emanations and in the headspace of urine, blood and cell and bacterial cultures. METHODS: Product ion distributions have been investigated by a SRI-TOF-MS instrument at an E/N in the drift tube reactor of 130 Td for both dry air and humid air (4.9% absolute humidity) used as the matrix gas. The investigated species were five monosulfides (dimethyl sulfide, ethyl methyl sulfide, methyl propyl sulfide, allyl methyl sulfide and methyl 5-methyl-2-furyl sulfide), dimethyl disulfide, dimethyl trisulfide, thiophene, 2-methylthiophene, 3-methylthiophene, methanethiol, allyl isothiocyanate, dimethyl sulfoxide, and two selenium compounds – dimethyl selenide and dimethyl diselenide. RESULTS: Charge transfer was seen to be the dominant reaction mechanism in all reactions under study forming the M(+) cations. For methanethiol and allyl isothiocyanate significant fractions were also observed of the stable adduct ions NO(+)M, formed by ion-molecule association, and [M–H](+) ions, formed by hydride ion transfer. Several other minor product channels are seen for most reactions indicating that the nascent excited intermediate (NOM)(+)* adduct ions partially fragment along other channels, most commonly by the elimination of neutral CH(3), CH(4) and/or C(2)H(4) species that are probably bound to an NO molecule. Humidity had little effect on the product ion distributions. CONCLUSIONS: The findings of this study are of particular importance for data interpretation in studies of volatile organosulfur and volatile organoselenium compounds employing SRI-TOF-MS in the NO(+) mode. © 2014 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd

Emission rates of selected volatile organic compounds from skin of healthy volunteers

AbstractGas chromatography with mass spectrometric detection (GC–MS) coupled with solid phase micro-extraction as pre-concentration method (SPME) was applied to identify and quantify volatile organic compounds (VOCs) emitted by human skin. A total of 64 C4-C10 compounds were quantified in skin emanation of 31 healthy volunteers. Amongst them aldehydes and hydrocarbons were the predominant chemical families with eighteen and seventeen species, respectively. Apart from these, there were eight ketones, six heterocyclic compounds, six terpenes, four esters, two alcohols, two volatile sulphur compounds, and one nitrile. The observed median emission rates ranged from 0.55 to 4790fmolcm−2min−1. Within this set of analytes three volatiles; acetone, 6-methyl-5-hepten-2-one, and acetaldehyde exhibited especially high emission rates exceeding 100fmolcm−2min−1. Thirty-three volatiles were highly present in skin emanation with incidence rates over 80%. These species can be considered as potential markers of human presence, which could be used for early location of entrapped victims during Urban Search and Rescue Operations (USaR)

Product ion distributions for the reactions of NO+ with some N-containing and O-containing heterocyclic compounds obtained using SRI-TOF-MS

AbstractProduct ion distributions for the reactions of NO+ with nine O-containing and six N-containing heterocyclic compounds present in human volatilome have been determined under the conditions of a Selective Reagent Ionization Time of Flight Mass Spectrometer (SRI-TOF-MS) at E/N values in the drift tube reactor ranging from 90 to 130Td. This study was undertaken to provide the kinetics data by which these heterocyclic compounds could be analyzed in biogenic media using SRI-TOF-MS. The specific heterocyclic compounds are furan, 2-methylfuran, 3-methylfuran, 2,5-dimethylfuran, 2-pentylfuran, 2,3-dihydrofuran, 1,3-dioxolane, 2-methyl-1,3-dioxolane, γ-butyrolactone, pyrrole, 1-methylpyrrole, pyridine, 2,6-dimethylpyridine, pyrimidine, and 4-methylpyrimidine. Charge transfer was the dominant mechanism in the majority of these NO+ reactions generating the respective M+ parent cation, but in the pyridine, pyrimidine, and 4-methylpyrimidine reactions, stable NO+M adduct ions were the major products with M+ ions as minor products. The reactions of dioxolanes with NO+ proceeded by hydride ion transfer only producing (M−H)+ ions. Fragmentation of the excited nascent product ions (M+)* did not occur for the majority of these reactions under the particular chosen conditions of the SRI-TOF-MS reactor, but partial fragmentation did occur in the 2,3-dihydrofuran and 2-pentylfuran reactions. However, lowering of the E/N in the drift tube suppresses fragmentation of (M+)* ions and promotes the formation of NO+M adduct ions, whereas increasing E/N has the opposite effect, as expected. The product ion distributions were seen to be independent of the humidity of the sample gas