Real-time breath gas analysis for pharmacokinetics: monitoring exhaled breath by on-line proton-transfer-reaction mass spectrometry after ingestion of eucalyptol-containing capsules

Abstract

Eucalyptol (1,8-cineole) is a common active agent in non-prescription pharmaceutical products that is employed to clear the airways during mucus blockages. Following ingestion of a eucalyptol-containing capsule, the capsule dissolves in the gut and transfers eucalyptol into the blood, which is subsequently expelled via the lungs, thus exposing this decongesting and inflammation-abating compound to the airways. The breath gas concentrations of eucalyptol in 11 healthy adult volunteers were monitored at regular intervals after capsule ingestion using on-line proton-transfer-reaction mass spectrometry (PTR-MS). Eucalyptol appeared in exhaled breath gas at varying times following ingestion, with its onset ranging from 1 h and 6 min to 4 h and 48 min (mean ± SD: 2.1 ± 0.5 h). Maximum concentrations also varied greatly, with peak eucalyptol levels between 106 and 1589 ppb(v) (mean ± SD: 489 ± 319 ppb(v)). These variations were not only inter-subject, but also intra-subject, i.e. repeated tests with the same participant yielded different onset times and a broad range of concentration maxima. A considerable contribution to these variations from infrequent sampling and analysis is discussed. This study characterized the temporal transfer of eucalyptol via the blood into the airways by examining exhaled breath and thereby demonstrated the suitability of on-line breath gas analyses, particularly PTR-MS, for certain pharmacokinetic investigations.

Allergic asthma exhaled breath metabolome: A challenge for comprehensive two-dimensional gas chromatography

“…From these, 134 compounds belonging to linear, ramified and cycloalkanes, alkenes, aldehydes, ketones and a group of miscellaneous compounds, were selected for further studies. The remaining compounds were considered as possible contaminants, as for example, aromatic compounds from environmental cumulative exposure [57], whereas terpenoids and esters can have its origin in ingested foods [58]. Otherwise, the linear, ramified and cycloalkanes, alkenes, aldehydes and ketones have been reported to be associated to several biochemical processes that may occur in humans [59].…”

Analytical challenges in breath analysis and its application to exposure monitoring

“…Some of these real-time methodologies allow responses to be obtained in less than 1 s [52]. Although most studies indicate LODs as being at the g/m 3 level [15,16,52,[54][55][56][57][58], some have proposed LODs at the ng/m 3 level [52,59,60]. Reynolds et al [55] have proposed the coupling of a thermal desorption unit to a real-time IMS instrument, as many compounds of interest are present at concentrations below the LODs for direct breath analysis.…”

Real-time breath gas analysis of CO and CO2 using an EC-QCL

“…True real-time detection requires a sampling and analysis system with low volume to ensure fast gas exchange times. Breath-cycle resolved, simultaneous detection of 1-3 compounds can today be achieved with the soft-ionization MS techniques [22,23] and laser spectroscopy [24][25][26][27], but only the latter method also offers the potential for compact and affordable instrumentation, which is desired in medical research and clinical practice.…”