Detection of Volatile Organic Compounds in Breath Using Thermal Desorption Electrospray Ionization-Ion Mobility-Mass Spectrometry

Abstract

A thermal desorption unit has been interfaced to an electrospray ionization-ion mobilitytime-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L-1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other. The combination of temperature programmed thermal desorption and ion mobility improved the response of selected species against background ions. Analysis of breath samples resulted in the identification of breath metabolites, based on ion mobility and accurate mass measurement using siloxane peaks identified during the analysis as internal lockmasses. IntroductionThe development of electrospray ionization (ESI) by Fenn and co-workers in 19841enabled the routine analysis of macromolecules and revolutionized the role mass spectrometry plays in the analysis of biological samples. It was suggested as early as 19862 that volatile organic compounds (VOCs) could also be ionized and detected with a high degree of sensitivity using ESI. However the first effective demonstration of the application of ESI to VOC analysis was not reported until 1994,3 when an ESI source was interfaced to an ion mobility spectrometer. Hill and co-workers further developed this approach, termed, secondary electrospray ionization (SESI),4 in conjunction with a hybrid ion mobility-quadrupole mass spectrometer, which they used to study a number of illicit 2 drugs. The charged droplets from the electrospray were reacted with the VOCs in a reaction cell placed immediately before the ion mobility drift cell. This work demonstrated that SESI could be used as an effective ionization method for both gas chromatography (GC) and liquid chromatography-mass spectrometry (LC-MS) experiments and that it was also more sensitive than standard electrospray for the analysis of VOCs. SESI was also later used to analyze vapors from explosives with detection limits at the sub-parts per trillion level, further demonstrating the high sensitivity of the approach.5 Recent work has shown that VOCs may be detected down to parts per quadrillion levels using electrospray ionization and that the ESI source parameters can be optimized to give selectivity toward specific ion species.6 Cooks et al. proposed an alternative approach, showed that EESI could be used to follow the concentration of an exhaled breath metabolite (urea) from breath to breath.12 In the same year, Zenobi and co-workers used EESI to look directly at exhaled breath and were able to detect involatile species such as carbohydrates which were present after eating a meal.13 The analysis of breath samples using gas chromatography/ mass spectrometry (GC/MS) has shown that a large number of VOCs may be detected and that VOC profiles in human breath are characterized by a huge degre...

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.…”

“…Pre-concentration on solid sorbents followed by thermal desorption (TD) is the most frequent method for the analysis of VOCs in breath samples [9][10][11][12][13]16,[19][20][21][22][23][24][25][26][27][28][43][44][45]47,55,62,75,[81][82][83][84][85]95,96]. Sorbent traps present the advantages that they can be prepared on a micro-scale and coupled on-line with a GC system to allow near real-time measurements [97][98][99][100][101], and the sorbent configuration can be easily changed to adapt to different compounds.…”

Real-Time Monitoring of Exhaled Volatiles Using Atmospheric Pressure Chemical Ionization on A Compact Mass Spectrometer

“…Moreover, the equipment required for GC-MS tends to be large, bulky and laboratory based that requires operation by specialist users. Interfacing of exhaled breath sampling to MS using ambient ionization techniques such as extractive electrospray ionization [14][15][16][17][18], atmospheric pressure chemical ionization (APCI-MS) [19][20][21] and glow discharge [22] has also been accomplished. These approaches can be readily interfaced to mass spectrometers with atmospheric pressure ionization sources to allow analysis of volatiles.…”

High throughput volatile fatty acid skin metabolite profiling by thermal desorption secondary electrospray ionisation mass spectrometry

“…The potential for rapidly generating high-fidelity mass spectra of exhaled breath VOC without a lengthy chromatography step was demonstrated [39], and the current work is informed by this approach, with the aim of describing the targeted analysis of VFAs present in and on human skin. The current research combined the sampling attributes of a 'skin patch' with thermal desorption secondary electrospray ionisation-mass spectrometry (TD-SESI-MS) [39]. TD-SESI-MS was found to have limits of detection no higher than 1 ng per sample, with an in-vivo RSD of 13.5%.…”