Analysis of volatile organic compounds in indoor environments using thermal desorption with comprehensive two‐dimensional gas chromatography and high‐resolution time‐of‐flight mass spectrometry

Building‐related health effects are frequently observed. Several factors have been listed as possible causes including temperature, humidity, light conditions, presence of particulate matter, and microorganisms or volatile organic compounds. To be able to link exposure to specific volatile organic compounds to building‐related health effects, powerful and comprehensive analytical methods are required. For this purpose, we developed an active air sampling method that utilizes dual‐bed tubes loaded with TENAX‐TA and Carboxen‐1000 adsorbents to sample two parallel air samples of 4 L each. For the comprehensive volatile organic compounds analysis, an automated thermal desorption comprehensive two‐dimensional gas chromatography high‐resolution time‐of‐flight mass spectrometry method was developed and used. It allowed targeted analysis of approximately 90 known volatile organic compounds with relative standard deviations below 25% for the vast majority of target volatile organic compounds. It also allowed semiquantification (no matching standards) of numerous nontarget air contaminants using the same data set. The nontarget analysis workflow included peak finding, background elimination, feature alignment, detection frequency filtering, and tentative identification. Application of the workflow to air samples from 68 indoor environments at a large hospital complex resulted in a comprehensive volatile organic compound characterization, including 178 single compounds and 13 hydrocarbon groups.     

二次纳流电喷雾电离耦合超高分辨质谱检测人体呼出气中相对高分子量化合物

二次电喷雾电离源耦合超高分辨质谱(SESI-UHRMS)有望检出人体呼出气中分子量大于300的相对高分子量化合物,这些化合物的发现将有助于更准确地理解呼出气中挥发性有机化合物(VOCs)的来源、产生机制以及SESI源电离机理,更好地实现SESI-UHRMS的转化应用.本研究自组装nanoSESI源(尚无商业产品)耦合四极杆-静电场轨道阱质谱(最高质量分辨率1.2×10~5),考察了该装置对健康人体呼出气中分子量为300~500化合物的检出情况.结果表明,所搭建的nanoSESI-UHRMS装置检测人体呼出气的重现性好、灵敏度高,可检出数十种分子量为300~500的化合物.根据这些化合物在单次呼气过程中信号强度随时间变化的趋势,推断其来源分别为内源性和外源性;各化合物的元素组成主要包括C,H,N和O,环-双键当量(RDB)的均值为(4.5±3.1),表明检出的化合物可能为醛酮或不饱和脂肪酸,容易在SESI源中被电离.本研究初步验证了自组建nanoSESI-UHRMS检测人体呼出气中相对高分子量化合物的可行性,为后续进一步开展方法应用奠定了基础.     

Determination of volatile organic compounds in human breath for Helicobacter pylori detection by SPME-GC/MS

Helicobacter pylori living in the human stomach release volatile organic compounds (VOCs) that can be detected in expired air. The aim of the study was the application of breath analysis for bacteria detection. It was accomplished by determination of VOCs characteristic for patients with H. pylori and the analysis of gases released by bacteria in suspension. Solid-phase microextraction was applied as a selective technique for preconcentration and isolation of analytes. Gas chromatography coupled with mass spectrometry was used for the separation and identification of volatile analytes in breath samples and bacterial headspace. For data calculation and processing, discriminant and factor analyses were used. Endogenous substances such as isobutane, 2-butanone and ethyl acetate were detected in the breath of persons with H. pylori in the stomach and in the gaseous mixture released by the bacteria strain but they were not identified in the breath of healthy volunteers. The canonical analysis of discrimination functions showed a strong difference between the three examined groups. Knowledge of substances emitted by H. pylori with the application of an optimized breath analysis method might become a very useful tool for noninvasive detection of this bacterium.     

Comparison of four extraction methods for analysis of volatile hop‐derived aroma compounds in beer

The volatile organic compound profile in beer is derived from hops, malt, yeast, and interactions between the ingredients, making it very diverse and complex. Due to the range and diversity of the volatile organic compounds present, the choice of the extraction method is extremely important for optimal sensitivity and selectivity. This study compared four extraction methods for hop‐derived compounds in beer late hopped with Nelson Sauvin. Extraction capacity and variation were compared for headspace solid‐phase micro extraction, stir bar sorptive extraction, headspace sorptive extraction, and solvent‐assisted flavor evaporation. Generally, stir bar sorptive extraction was better suited for acids, headspace sorptive extraction for esters and aldehydes, while headspace solid‐phase microextraction was less sensitive overall, extracting 40% fewer compounds. Solvent‐assisted flavor evaporation with dichloromethane was not suitable for the extraction of hop‐derived volatile organic compounds in beer, as the profile was strongly skewed towards alcohols and acids. Overall, headspace sorptive extraction is found to be best suited, closely followed by stir bar sorptive extraction.     

An adaptive breath sampler for use with human subjects with an impaired respiratory function

An adaptive sampler for collecting 2.5 dm(3) samples of exhaled air from human subjects with an impaired respiratory function is described. Pressure in the upper respiratory tract is continuously monitored and the data used to control an automated system to collect select portions of the expired breathing cycle onto a mixed bed Tenax(trade mark) and Carbotrap(trade mark) adsorbent trap for analysis by GC-MS. The sampling approach is intended for use in metabolomic profiling of volatiles in human breath at concentrations greater than microg m(-3). The importance of experimental reproducibility in metabolomic data is emphasised and consequently a high purity air supply is used to maintain a stable exogenous volatile organic compound profile at concentrations in the range 5 to 30 microg m(-3). The results of a 90 day stability study showed that exogenous VOCs were maintained at significantly lower levels (40 times lower for isopropyl alcohol) and with significantly higher reproducibility (80 times lower standard deviation for isopropyl alcohol) than would have been be the case if ambient air had been used. The sampling system was evaluated with healthy controls alongside subjects with chronic obstructive pulmonary disease. Subjects were able to breathe normally with control subjects observed to breathe at a rate of 9 to 17 breaths per minute, compared to 16 to 30 breaths per minute for subjects with COPD. This study presents, for the first time, observations and estimates of intra-subject breath sample reproducibility from human subjects. These reproducibility studies indicated that VOCs in exhaled breath exhibit a variety of dynamic behaviours, with some species recovered with a RSD <30%, while other species were observed to have significantly more variable concentrations, 30 to 130% RSD. The approach was also demonstrated to reliably differentiate the differences in the VOC profiles between alveolar and dead space air.     

Chemotherapy control by breath profile with application of SPME‐GC/MS method

Chemotherapy used as a treatment against lung cancer has influence on metabolic processes occurring in healthy cells. The changes of biochemical pathways proceeded inside cells might be observed in expired air. In the experiment, breath analysis was carried out before and after anticancer therapy. Expired air samples were collected from 22 patients with a biopsy confirmed lung cancer. Volatile organic compounds present in breath were analyzed by gas chromatography/mass spectrometry. For enrichment of analytes solid‐phase microextraction technique was applied. Eight fibers covered by different sorbents were tested. Carboxen‐polydimethylsiloxane fiber revealed the highest extraction efficiency in relation to analytes in breath. The data showed that cytostatic drugs increase the concentration of acetone and isoprene in the breath collected after chemotherapy. Volatile metabolites of administrated drugs were not identified in expired air.     

人体呼出气中挥发性有机化合物的检测方法

呼出气检测作为一种潜在的新型临床检测手段受到广泛关注。本文详细综述了人体呼出气中挥发性有机化合物(VOCs)的各类检测方法和技术,分别对色谱法、质谱法和光谱及传感器法的原理、特点和最新研究进展进行了介绍,对照总结了目前已确定的异戊二烯、丙酮等疾病生物标志物的各种分析方法和实测数据,并展望了未来的研究动向。     

The analysis of volatile trace compounds in landfill gases,compost heaps and forest air

Landfill gas, cryotrapped on a loop fashioned from a length of a capillary gas chromatography (GC) column, was examined for volatile organometallic compounds (VOMCs) and for volatile organic compounds (VOCs) by using GC–mass spectrometry (MS). A large number of organic components were present and many were identified, but the only VOMCs present in high enough concentrations to be detected were trimethylstibine and tetramethyltin. The use of inductively coupled plasma (ICP)‐MS as an element‐specific detector allowed the identification of a number of other organometallic species in the landfill gas, including trimethylarsine and trimethylbismuth, and, for the first time, butyltrimethyltin and dibutyldimethyltin. The presence of molybdenum hexacarbonyl was confirmed. Gas from a large‐scale compost heap and from compost incubated in the laboratory contained iodomethane but no common VOMCs (GC–ICP‐MS). Only VOCs were present in forest air (GC–MS). Copyright © 2003 John Wiley & Sons, Ltd.     

Analysis of human breath with micro extraction techniques and continuous monitoring of carbon dioxide concentration

The detection of volatile organic compounds (VOCs) in human breath can be useful for the clinical routine diagnosis of several diseases in a non-invasive manner. Traditional methods of breath analysis have some major technical problems and limitations. Membrane extraction with a sorbent interface (MESI), however, has many advantages over current methods, including good selectivity and sensitivity, and is well suited for breath analysis. The aim of this project was to develop a simple and reproducible sampling device and method based on the MESI system for breath analysis. The feasibility and validity of the MESI system was tested with real human breath samples. Internal standard calibration methods were used for the quantitative analysis of various breath samples. Calibration curves for some main components (target analytes such as acetone and pentane) were determined in the research. The optimized stripping-side and feeding-side gas velocities were determined. The use of breath CO₂ as an internal standard for the analysis of breath VOCs is an effective method to solve the difficulties associated with variations in the target analyte concentrations in a sample, which are attributed to mass losses and different breathing patterns of different subjects. In this study, the concentration of breath acetone was successfully expressed normalized to CO₂ as in the alveolar air. Breath acetone of healthy males and females profiled at different times of the day was plotted using the MESI system, and results were consistent with the literature. This technique can be used for monitoring breath acetone concentrations of diabetic patients and for applications with other biomarker monitoring.     

Identification of volatile lung cancer markers by gas chromatography–mass spectrometry: comparison with discrimination by canines

In this work, a chromatographic method for identification of volatile organic compounds was compared with canine recognition. Gas chromatography and mass spectrometry (GC-TOF MS) were used for determination of concentrations of trace gases present in human breath. The technique enables rapid determination of compounds in human breath, at the parts per billion level. Linear correlations were from 0.83-234.05 ppb, the limit of detection was the range 0.31-0.75 ppb, and precision, expressed as relative standard deviation (RSD), was less than 10.00 %. Moreover, trained dogs are able to discriminate breath samples of patients with diagnosed cancer. We found a positive correlation between dog indications and the ethyl acetate and 2-pentanone content of breath (r = 0.85 and r = 0.97, respectively). The methods presented for detection of lung cancer markers in exhaled air could be used as a potential non-invasive tool for screening. In addition, the canine method is relatively simple and inexpensive in comparison with chromatography.     

Volatile Organic Compounds Analysis in Breath Air in Healthy Volunteers and Patients Suffering Epidermoid Laryngeal Carcinomas

Exhaled breath contains thousands of gaseous volatile organic compounds (VOCs) that may be used as non-invasive markers of head and neck epidermoid cancer. We hypothesized that solid phase micro-extraction coupled to gas chromatography–mass spectrometry can discriminate patients with epidermoid head and neck cancer from healthy controls by analyzing the gaseous volatile organic compounds, VOC-profile, in exhaled breath, thus identifying some non-invasive biomarkers to be used in early detection. Twenty healthy subjects participated in a cross-sectional study plus 11 patients with epidermoid supraglottic laryngeal cancer. VOCs from T3 supraglottic cancer were clustered distinctly from those of T1 and healthy subjects. Up to seven VOCs were detected differently from healthy volunteers, mainly 2-butanone and ethanol. Thus VOC-patterns of exhaled breath may discriminate patients with epidermoid head and neck cancer from healthy controls.     

A Method of Determining the Efficiency of Air Sampling Traps to Collect and Release Volatile Organic Compounds

Abstract

A new method is described that facilitates determining the efficiency of air sampling traps to adsorb and thermally desorb volatile organic compounds. A known volume of a liquid standard of volatile organic compounds is vaporized into an air stream, a fraction of which is collected on an air sampling trap. This trap is subsequently thermally desorbed and analyzed using a GC/FID. The efficiency of the trap to adsorb and thermally desorb each compound tested is calculated.     

A New Cell for Single Sided Headspace Sampling and Evaluation of Barrier Function in Laminated Paperboard

A new cell for single sided headspace sampling has been developed for the analysis of volatile organic compounds from food packaging paperboard and laminated paperboard. The cell, which samples the volatile organic compounds over a selected surface, is useful for determining the barrier function of laminated paperboards with respect to volatile compounds. The analysis of volatile organic compounds is carried out by purge and trap capillary gas chromatography in combination with mass spectrometric detection and compound identification. The new sampling cell was constructed to facilitate specific analysis of organic compounds from only one side of a laminated paperboard. The construction and the operating principles of the new sampling device are described. The repeatability of the single sided headspace procedure was found to be quite good. Relative standard deviations of about 5–7% were obtained for the major compounds quantified in replicate headspace analyses of a laminated paperboard. The volatile compounds released from the inner side of a food packaging paperboard sample with different surface composition on the two sides were determined. The barrier function against volatile organic compounds of some laminated paperboards was investigated employing the new headspace cell.     

One-year time series of investigations of analytes within human breath using ion mobility spectrometry

Ion mobility Spectrometry is used to detect volatile analytes within human breath directly. Many volatile organic compounds (VOC) show significant day-to-day variation in the signal height related to the concentration of the analyte, although the breath collection had been performed under the same conditions with respect to similar sampling procedure, similar dead volume, similar measurement time, and measurement conditions. Variations of 8 different analytes are investigated over a time period of 11 months in the exhaled breath of the same person in the same room environment. The individual variability is reported for Benzothiazole; D-Limonene; Eucalyptol; Decamethylcyclopentasiloxane; Decanal; 1-Hexanol, 2-ethyl-; Cyclohexanone, 5-methyl-2-(1-methylethyl) and Nonanal. The paper shows, that the individual variability must be taken into consideration to relate the findings to medical questions. Therefore, the room air concentration of VOCs must be taken into account, so that the difference between exhaled and inhaled air has to be used as indicator. Finally, starting with individual variabilities, the normal variation related to the specific analyte should be considered in addition.     

Identification and quantification of VOCs by proton transfer reaction time of flight mass spectrometry: An experimental workflow for the optimization of specificity,sensitivity, and accuracy

Proton transfer reaction time of flight mass spectrometry (PTR‐ToF‐MS) is a direct injection MS technique, allowing for the sensitive and real‐time detection, identification, and quantification of volatile organic compounds. When aiming to employ PTR‐ToF‐MS for targeted volatile organic compound analysis, some methodological questions must be addressed, such as the need to correctly identify product ions, or evaluating the quantitation accuracy. This work proposes a workflow for PTR‐ToF‐MS method development, addressing the main issues affecting the reliable identification and quantification of target compounds. We determined the fragmentation patterns of 13 selected compounds (aldehydes, fatty acids, phenols). Experiments were conducted under breath‐relevant conditions (100% humid air), and within an extended range of reduced electric field values (E/N = 48–144 Td), obtained by changing drift tube voltage. Reactivity was inspected using H₃O⁺, NO⁺, and O₂⁺ as primary ions. The results show that a relatively low (<90 Td) E/N often permits to reduce fragmentation enhancing sensitivity and identification capabilities, particularly in the case of aldehydes using NO⁺, where a 4‐fold increase in sensitivity is obtained by means of drift voltage reduction. We developed a novel calibration methodology, relying on diffusion tubes used as gravimetric standards. For each of the tested compounds, it was possible to define suitable conditions whereby experimental error, defined as difference between gravimetric measurements and calculated concentrations, was 8% or lower.     

Development of a method for the monitoring of odor‐causing compounds in atmospheres surrounding wastewater treatment plants

This study describes the development of an analytical method based on active collection in a multisorbent Tenax TA/Carbograph 1TD tube, followed by thermal desorption and GC‐MS for the determination of 16 volatile organic compounds in air samples. The analyzed compounds include ozone precursors and odor‐causing compounds belonging to different chemical families (sulfur‐ and nitrogen‐containing compounds, aldehydes, and terpenes). Two types of sorbents were tested and desorption conditions (temperature, time, and sampling, and desorption flow) were evaluated. External calibration was carried out using the multisorbent bed. Method detection limits in the range 0.2–2.0 μg m^?3 for 1 L samples were obtained. The method was applied for determining the target compounds in air samples from two different wastewater treatment plants. Most compounds were detected and toluene, limonene, and nonanal were found in particularly high concentrations with maximum values of 438, 233, and 382 μg m^?3, respectively.     

Analysis of exhaled breath from smokers,passive smokers and non‐smokers by solid‐phase microextraction gas chromatography/mass spectrometry

In this study, 38 samples of expired air were collected and analyzed from 20 non‐smoking volunteers, four passive smokers and 14 smokers (21 women and 17 men). Measurements were carried out using solid‐phase microextraction (SPME) as an isolation and preconcentration technique. The determination and identification were accomplished by gas chromatography coupled with mass spectrometry (GC/MS). Our data showed that ca 32% of all identified compounds in the breath of healthy non‐smokers were saturated hydrocarbons. In the breath of smoking and passive smoking volunteers hydrocarbons were predominant, but also present were more exogenous analytes such as furan, acetonitrile and benzene than in the breath of non‐smokers. Acetonitrile, furan, 3‐methylfuran, 2,5‐dimethylfuran, 2‐butanone, octane and decane were identified in breath of smoking and passive smoking persons. Copyright © 2008 John Wiley & Sons, Ltd.     

Application of femtosecond laser mass spectrometry to the analysis of volatile organic compounds

Femtosecond (fs) lasers have high intensity and ultrashort pulse duration. Tunneling ionization occurs for molecules subject to such intense laser fields. We have studied the mass spectra of a variety of molecules irradiated by intense fs laser pulses. These molecules include some typical volatile organic compounds contained in human breath and in the atmosphere. The results demonstrate that all of these molecules can be ionized by intense fs laser pulses. Dominant parent ion and some characteristic ionic fragments are observed for each molecule. The degree of fragmentation can be controlled by adjusting the laser intensity. Moreover, saturation ionization can occur for each molecule by increasing the laser intensity. These features indicate that fs laser mass spectrometry can be a sensitive tool to identify and quantify volatile organic compounds in human breath.     

Significant different volatile biomarker during bronchoscopic ion mobility spectrometry investigation of patients suffering lung carcinoma

Exhaled breath of patients suffering non-small bronchial carcinoma contains volatile organic compounds (VOC) different from healthy people. VOCs could be detected using ion mobility spectrometry down to the pg/L range even in air directly. To date, the origin of the different VOCs found is insecure. Such VOCs could be a direct product of the metabolism of the tumor or relatable to mostly present co-factors like infections or necrosis or a reaction of the human organism to the tumor (e.g. oxidativ stress). In the present study the breath of 19 patients suffering from confirmed NSCLC (non-small-cell lung carcinoma) with different histological types was investigated. In all cases flexible video-chip bronchoscopy was realized. Before taking samples for histological investigations in the lung on both main bronchi, samples of air were taken using a polytetrafluoroethylene (PTFE or Teflon) tube as catheter directly from the working channel of a bronchoscope and connected directly to the inlet of the ion mobility spectrometer. The measurement was started immediately. In total, 72 common peaks could be identified. 5 Peaks were significantly varying between the tumor site and the collateral lung. Considering adenocarcinoma, one peak separates both sites clearly and was relatable to the dimer of n-Dodecane. Two peaks were found on squamous cell carcinoma and relatable to 2-Butanol or 2-Methylfuran and Nonanal. The sensitivity, specificity, positive and negative predictive values were, for adenocarcinoma 100%, 75%, 80% and 100%, respectively – for squamous cell carcinoma 78%/78%, 67%/78%, 70%/80% and 75%/88%, for 2-Butanol and Nonanal respectively. Therefore, VOCs obtained from bronchoscopic sampling of breath could be detected using ion mobility spectrometry. The present study suggests that lung carcinoma with different histology will be represented by different volatile analytes.     

Comprehensive Two-Dimensional Gas Chromatography–Mass Spectrometry Analysis of Exhaled Breath Compounds after Whole Grain Diets

Exhaled breath is a potential noninvasive matrix to give new information about metabolic effects of diets. In this pilot study, non-targeted analysis of exhaled breath volatile organic compounds (VOCs) was made by comprehensive two-dimensional gas chromatography–mass spectrometry (GCxGC-MS) to explore compounds relating to whole grain (WG) diets. Nine healthy subjects participated in the dietary intervention with parallel crossover design, consisting of two high-fiber diets containing whole grain rye bread (WGR) or whole grain wheat bread (WGW) and 1-week control diets with refined wheat bread (WW) before both diet periods. Large interindividual differences were detected in the VOC composition. About 260 VOCs were detected from exhaled breath samples, in which 40 of the compounds were present in more than half of the samples. Various derivatives of benzoic acid and phenolic compounds, as well as some furanones existed in exhaled breath samples only after the WG diets, making them interesting compounds to study further.