A novel coupling technique based on thermal desorption gas chromatography with mass spectrometry and ion mobility spectrometry for breath analysis.

Exhaled breath analysis is evolving into an increasingly important non-invasive diagnostic tool. Volatile organic compounds (VOCs) in breath contain information about health status and are promising biomarkers for several diseases, including respiratory infections caused by bacteria. To monitor the composition of VOCs in breath or the emission of VOCs from bacteria, sensitive analytical techniques are required. Next to mass spectrometry, ion mobility spectrometry (IMS) is considered a promising analytical tool for detecting gaseous analytes in the parts per billion by volume to parts per trillion by volume range. This work presents a new, dual coupling of thermal desorption gas chromatography to a quadrupole mass spectrometer (MS) and an IMS by operating a simple splitter. Nearly identical retention times can be reached in the range of up to 30 min with slight deviations of 0.06 min-0.24 min. This enables the identification of unknown compounds in the IMS chromatogram using unambiguous mass spectral identification, as there are still no commercially available databases for IMS. It is also possible to discriminate one of the detectors using the splitter to improve detection limits. Using a test liquid mixture of seven ketones, namely 2-butanone, 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone with a concentration of 0.01 g l-1reproducibilities ranging from 3.0% to 7.6% for MS and 2.2%-5.3%, for IMS were obtained, respectively. In order to test the system optimized here for the field of breath analysis, characteristic VOCs such as ethanol, isoprene, acetone, 2-propanol, and 1-propanol were successfully identified in exhaled air using the dual detector system due to the match of the corresponding IMS, and MS spectra. The presented results may be considered to be a starting point for the greater use of IMS in combination with MS within the medical field.

Making Every Single Puff Count-Simple and Sensitive E-Cigarette Aerosol Sampling for GCxIMS and GC-MS Analysis.

The analysis of the aerosol from tobaccoless electronic cigarettes (e-cigarettes) is an important part of understanding their impact on human health, yet sampling aerosol from e-cigarettes is still considered a challenge. It lacks a standard method for research and quality control and there are a variety of methods. However, few are simple and inexpensive, and none have been suggested for the use with gas chromatography coupled ion mobility spectrometry (GCxIMS). This work presents and evaluates such a setup made from standard lab equipment to quickly collect a quantitative sample from the aerosol of a single puff (5 s totaling 125 mL). The aerosol condensates directly in the cooled headspace (HS) vial, which is analyzed in the HS-GCxIMS or mass spectrometer (HS-GC-MS). The combined use of GC-MS and GCxIMS allows the simple and sensitive identification of unknown substances in complex mixtures and the identification of degradation products in the aerosols. A calibration of 26 flavor compounds (0.2-20 µg/g) was created using single puffs of a spiked, flavorless commercial refill solution and 2-alkanones as internal standards. This sensitive but easily reproducible setup enables a wide range of further investigations, even for labs that were previously unable to afford it.

Quantitation of Flavor Compounds in Refill Solutions for Electronic Cigarettes Using HS-GCxIMS and Internal Standards.

New regulations on the use of flavor compounds in tobaccoless electronic cigarettes require comprehensive analyses. Gas chromatography coupled ion mobility spectrometry is on the rise as an analytical technique for analyzing volatile organic compounds as it combines sensitivity, selectivity, and easy usage with a full-range screening. A current challenge is the quantitative GCxIMS-analysis. Non-linear calibration methods are predominantly used. This work presents a new calibration method using linearization and its corresponding fit based on the relation between the reactant and analyte ions from the chemical ionization. The analysis of e-liquids is used to compare the presented calibration with an established method based on a non-linear Boltzmann fit. Since e-liquids contain matrix compounds that have been shown to influence the analyte signals, the use of internal standards is introduced to reduce these effects in GCxIMS-analysis directly. Different matrix mixtures were evaluated in the matrix-matched calibration to improve the quantitation further. The system's detection and quantitation limits were determined using a separate linear calibration. A matrix-matched calibration series of 29 volatile compounds with 12 levels were used to determine the concentration of these substances in a spiked, flavorless e-liquid and a banana-flavored e-liquid, validating the quality of the different calibrations.

Differentiation of Monofloral Honey Using Volatile Organic Compounds by HS-GCxIMS.

Honey is a natural product and can be described by its botanical origin, determined by the plants from which the bees collect nectar. It significantly influences the taste of honey and is often used as a quality criterion. Unfortunately, this opens up the possibility of food fraud. Currently, various methods are used to check the authenticity of monofloral honey. The laborious, manual melissopalynology is considered an essential tool in the verification process. In this work, the volatile organic compounds obtained from the headspace of honey are used to prove their authenticity. The headspace of 58 honey samples was analyzed using a commercial easy-to-use gas chromatography-coupled ion mobility spectrometer with a headspace sampler (HS-GCxIMS). The honey samples were successfully differentiated by their six different botanical origins using specific markers with principal component analysis in combination with linear discriminant analysis. In addition, 15 honey-typical compounds were identified using measurements of reference compounds. Taking a previously published strategy, retention times of marker compounds were correlated with GC-coupled mass spectrometry (GC-MS) measurements to assist in the identification process.

Strategy for the identification of flavor compounds in e-liquids by correlating the analysis of GCxIMS and GC-MS.

This work presents a strategy to correlate the results from gas chromatography coupled ion mobility spectrometry (GCxIMS) and mass spectrometry (GC-MS) to enable a simpler and cheaper analysis of flavor compounds in e-liquids. The use of the retention index for GCxIMS measurements was validated for its application to correlate results with GC-MS data. The easy detection of the GCxIMS for substances at concentrations as low as 1 µg/L can therefore be combined with the identification power of the MS. The use of the MS' mass signals and wide-spread availability of mass spectra libraries reduces the effort necessary to choose the correct reference standards for the identification of unknown substances. Between both detectors, correlating of the retention time indices was achieved for ± 1%. 2-Alkanones were used as an alternative reference point for the IMS and the well-established alkanes for the MS. The application on flavor compounds in e-liquids shows equal or better results than those presented for more complex, hardware-based correlations like line splitting. Additionally, the inverted reduced mobility combined with the retention index of a non-polar column enables simple extrapolation for the confirmation of expected substances as well as the use in a transferable database. For the first time, this comprehensive application allows an extensive, simplified, and cheap identification of flavor compounds in e-liquids by GCxIMS and GC-MS.

Analysis of e-liquids for electronic cigarettes using GC-IMS/MS with headspace sampling.

Electronic cigarettes (e-cigarettes) are continuously increasing in popularity due to being considered healthier compared with traditional cigarettes. Based on the European directive 2014/40/EU [1] the German legislation restricts the usage of potential harmful substances in these tobacco related products [2,3]. The aim of this work was to establish a method for the detection and quantification of selected substances covered by the above regulation. For this purpose, one-of-a-kind gas chromatograph with ion mobility spectrometer (GC-IMS) was used. Instrument was parallelly coupled with conventional chromatograph equipped with quadrupole mass spectrometer (GC-MS). Headspace (HS) was used as a sample preparation technique. During initial tests both systems were correlated by using a mixture of simple carbonyl compounds. The identification of the selected analytes was performed by mass spectrometry and calibration curves for the quantification were recorded. For all tested substances the limit of detection (LOD) and limit of quantification (LOQ) were determined. The LOD ranges are from 8 to 70 µg/L, the LOQ are from 25 to 200 µg/L. For testing the usability of the developed method 20 samples of commercially available refills for e-cigarettes (e-liquids), produced in Germany and Poland, were analyzed. Substances listed in the directive were found in all samples. In two of them an according to the regulations forbidden substance (estragole) was detected.

On-line headspace-multicapillary column-ion mobility spectrometry hyphenation as a tool for the determination of off-flavours in foods.

In this work, an ion mobility spectrometer (IMS) with a tritium ionization source on-line coupled to a headspace (HS) autosampler and a multicapillary column (MCC) was evaluated for the monitoring of lipid oxidation products in milk with different flavours (cacao, fruits, cereals and nuts) and linseed oil samples enriched with omega-3 acids. In this combination, the multicapillary column is used as an interface between the HS and the IMS, providing the efficient separation of the volatile compounds. In this way, the proposed method permits the detection of hexanal, 2-butanone, acetone and dimethyl sulfide as representative degradation products. The limits of detection were in the interval 0.3 µg L(-1) (for hexanal in milk) to 3.0 µg L(-1) (for dimethyl sulfide in linseed oil) while the limits of quantification varied between 1.1 µg L(-1) (for hexanal in milk) and 9.6 µg L(-1) (for dimethyl sulfide in linseed oil). The precision of the method was evaluated as relative standard deviation and the values were better than 8% in all cases. The evolution of the volatiles profile during 36 days under different storage conditions (temperature, oxygen and light) demonstrates the capability of the HS-MCC-IMS coupling for the estimation of the degradation of the samples. After the degradation study, it can be concluded that the stability of the milk samples during storage is more affected by the light while temperature was more critical for oil samples.

Detection of metabolites of trapped humans using ion mobility spectrometry coupled with gas chromatography.

For the first time, ion mobility spectrometry coupled with rapid gas chromatography, using multicapillary columns, was applied for the development of a pattern of signs of life for the localization of entrapped victims after disaster events (e.g., earthquake, terroristic attack). During a simulation experiment with entrapped volunteers, 12 human metabolites could be detected in the air of the void with sufficient sensitivity to enable a valid decision on the presence of a living person. Using a basic normalized summation of the measured concentrations, all volunteers involved in the particular experiments could be recognized only few minutes after they entered the simulation void and after less than 3 min of analysis time. An additional independent validation experiment enabled the recognition of a person in a room of ∼25 m(3) after ∼30 min with sufficiently high sensitivity to detect even a person briefly leaving the room. Undoubtedly, additional work must be done on analysis time and weight of the equipment, as well as on validation during real disaster events. However, the enormous potential of the method as a significantly helpful tool for search-and-rescue operations, in addition to trained canines, could be demonstrated.

Direct classification of olive oils by using two types of ion mobility spectrometers.

In this work, we explored the use of an Ion Mobility Spectrometry (IMS) device with an ultraviolet (UV) source, and of a Gas Chromatographic (GC) column coupled to an IM Spectrometer with a tritium source, for the discrimination of three grades of olive oil, namely: extra virgin olive oil (EVOO), olive oil (OO) and pomace olive oil (POO). The three types of oil were analyzed with both equipment combinations as coupled to a headspace system and the obtained ion mobility data were consecutively processed with various chemometric tools. The classification rate for an independent validation set was 86.1% (confidence interval at 95% [83.4%, 88.5%]) with an UV-IMS and 100% (confidence interval at 95% [87%, 100%]) using a GC-IMS system. The classification rate was improved by using a more suitable ionization source and a pre-separation step prior to the IM analysis.

Detection of human metabolites using multi-capillary columns coupled to ion mobility spectrometers.

The human breath contains indicators of human health and delivers information about different metabolism processes of the body. The detection and attribution of these markers provide the possibility for new, non-invasive diagnostic methods. In the recent study, ion mobility spectrometers are used to detect different volatile organic metabolites in human breath directly. By coupling multi-capillary columns using ion mobility spectrometers detection limits down to the ng/L and pg/L range are achieved. The sampling procedure of human breath as well as the detection of different volatiles in human breath are described in detail. Reduced mobilities and detection limits for different analytes occurring in human breath are reported. In addition, spectra of exhaled air using ion mobility spectrometers obtained without any pre-concentration are presented and discussed in detail. Finally, the potential use of IMS with respect to lung infection diseases will be considered.

Detection of the gasoline components methyl tert-butyl ether, benzene, toluene, and m-xylene using ion mobility spectrometers with a radioactive and UV ionization source.

For the first time, ion mobility spectrometers (IMS) with radioactive and UV ionization sources in combination with multicapillary columns (MCCs) have been used to determine methyl tert-butyl ether (MTBE), a gasoline additive, in water and nitrogen as well as the monoaromatic compounds benzene, toluene, and m-xylene (BTX). A membrane extraction unit was set up to extract the substances from water, which is simple, effective, and easy to automate for further applications. Thus, the detection of MTBE and BTX of gasoline vapors was accomplished after a preliminary silicone membrane extraction. Two-dimensional data analyses of IMS-chromatograms allow us to separate these substances clearly according to their different retention and drift times. Method detection limits for MTBE were 2 microg/L (UV) and 30 pg/L (63Ni) in nitrogen and 20 mg/L (UV) and 1 microg/L (63Ni) in water. Rather a good reproducibility was achieved with relative standard deviations of between 2.9 and 9%. The method presented in this article has been proven to be suitable for nearly real-time monitoring as the total analysis time is less than 90 s. As an example of application, the detection of MTBE and BTX in a mixture of volatile organic compounds of pure gasoline using the 2-D IMS-chromatogram is presented.