Detection of isoprene in expired air from human subjects using proton-transfer-reaction mass spectrometry

Abstract

A new analytical method using proton-transfer-reaction mass spectrometry (PTRMS) is described for the determination of trace constituents in human breath. PTRMS is sufficiently sensitive and specific that it does not require preconcentration or separation. At its present stage of development it is capable of detecting trace constituents present in air at the part-per-billion level. These capabilities are illustrated for isoprene, one of the most abundant endogenous hydrocarbons. Our results confirm recent observations of a diurnal level variation associated with sleep or wakefulness; a new finding is that young children have much lower levels of isoprene in breath than adults. To address the metabolic origin of human isoprene, we used PTRMS to analyze expired air for allylic C5 alcohols that have been proposed to be non-enzymatic precursors of isoprene. The lack of correlation between peak breath isoprene and these alcohols suggests that the hydrocarbon is formed by some other mechanism.

Potential applications of breath isoprene as a biomarker in modern medicine: a concise overview

“…Several gas chromatographic methods coupled to flame ionization detection (FID), UV detection, photoionization detector (PID) or mass spectrometry (MS) [1,23,24], proton transfer MS (PTR-MS) [14], or selected ion flow tube (SIFT)-MS [25] have been described in the literature for determination of isoprene in expired breath, which appear to have variable levels of sensitivity and specificity. The PTR-MS was developed as an analytical method for the determination of trace constituents in human breath, including isoprene, at the ppb level [14,[26][27][28].…”

“…The PTR-MS was developed as an analytical method for the determination of trace constituents in human breath, including isoprene, at the ppb level [14,[26][27][28]. Compared to gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS) methods [29], PTR-MS is sufficiently sensitive and specific that it doesn't require pre-concentration or separation of the sample and therefore the volatile organic compounds can be measured on line and breath isoprene levels can be obtained every few seconds [14].…”

“…The PTR-MS was developed as an analytical method for the determination of trace constituents in human breath, including isoprene, at the ppb level [14,[26][27][28]. Compared to gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS) methods [29], PTR-MS is sufficiently sensitive and specific that it doesn't require pre-concentration or separation of the sample and therefore the volatile organic compounds can be measured on line and breath isoprene levels can be obtained every few seconds [14]. In addition, SIFT-MS analyses breath for the major breath metabolites and provides a measure of their alveolar concentration, both simply and directly, from only a single exhalation in real time, without the need to collect large volumes of breath, which are sometimes difficult to acquire, and without preconcentration of the breath metabolites on some form of trap as is generally required for analysis by GC-MS, and also avoiding bag sampling [30][31][32][33].…”

“…It is a major hydrocarbon found in human breath [12]; however the breath concentration of isoprene has a large inter-individual variability. Children, aged 4-6 y, have an average breath isoprene concentration of < 20 parts per billion (ppb) [13]; whereas adult values range from ~50 up to 1,000 ppb [14,15]. Within the adult age-group, there is little evidence for an age dependence of breath isoprene concentration [15][16][17].…”

“…Within the adult age-group, there is little evidence for an age dependence of breath isoprene concentration [15][16][17]. Furthermore, the amount of isoprene eliminated via the breath does not appear to be influenced by gender, diet or fasting [12], but rather by smoking [18], physical exercise [19], sleep and wakefulness patterns [14,19].…”