20 research outputs found
On-line Breath Metabolomics in Respiratory Diseases using Secondary Electrospray Ionization-Mass Spectrometry
Every second we are exhaling hundreds of endogenous and exogenous compounds that originate from blood and lung tissue. Obtaining metabolic information via exhaled breath analysis has been an emerging topic since the 1970s. Secondary electrospray ionization-mass spectrometry is a relatively new technique to detect these metabolites on-line in a highly sensitive and specific fashion. Using this technique, several respiratory diseases, including chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, asthma, and lung cancer have been investigated over the past years. Several new potential biomarkers for these diseases were identified and new metabolic insights into their pathophysiology could be obtained.ISSN:0009-429
Secondary electrospray ionization proceeds: Via gas-phase chemical ionization
Our main goal was to gain further insights into the mechanism by which gas-phase analytes are ionized by interaction with plumes of electrospray solvents. We exposed target vapors to electrosprays of either water or deuterated water and mass analyzed them. Regardless of the solvent used, the analytes were detected in protonated form. In contrast, when the ionization chamber was humidified with deuterated water, the target vapors were detected in deuterated form. These observations suggest that either there is no interaction between analytes and electrospray charged droplets, or if there is any, a subsequent gas-phase ion–molecule reaction governs the process. Implications in practical examples such as breath analysis are discussed.ISSN:1759-9660ISSN:1759-967
Detection of Volatile Organic Compounds with Secondary Electrospray Ionization and Proton Transfer Reaction High-Resolution Mass Spectrometry: A Feature Comparison
The analysis of volatiles is of high relevance for a wide range of applications from environmental air sampling and security screening to potential medical applications. High-resolution mass spectrometry methods offer a particularly wide compound coverage, sensitivity, and selectivity. Online approaches allow direct analysis in real time without the need for sample preparation. For the first time, we systematically compared the analysis of volatile organic compounds with secondary electrospray ionization (SESI) and proton transfer reaction (PTR) high-resolution mass spectrometry. The selected instruments had comparable mass resolving powers with m/Δm ≥ 15000, which is particularly suitable for nontargeted analysis, for example, of exhaled breath. Exhalations from 14 healthy adults were analyzed simultaneously on both instruments. In addition, 97 reference standards from nine chemical classes were analyzed with a liquid evaporation system. Surprisingly, in breath, we found more complementary than overlapping features. A clear mass dependence was observed for each method with the highest number of detected m/z features for SESI in the high mass region (m/z = 150-250) and for PTR in the low mass region (m/z = 50-150). SESI yielded a significantly higher numbers of peaks (828) compared to PTR (491) among a total of 1304 unique breath m/z features. The number of signals observed by both methods was lower than expected (133 features) with 797 unique SESI features and 374 unique PTR features. Hypotheses to explain the observed mass-dependent differences are proposed
Metabolic effects of inhaled salbutamol determined by exhaled breath analysis
We explore whether real-time breath analysis by high resolution mass spectrometry is suitable to monitor changes at the metabolic level due to inhaling bronchodilator medication. We compared the breath levels of metabolites in a group of patients (n = 50) at baseline and 10 and 30 min after inhalation of 200 μg salbutamol. The same procedure was performed with a group of controls (n = 48) inhaling a placebo spray. A total of 131 mass spectral features were significantly altered as a result of inhaling medication, but not after inhaling placebo. We found that homologous series of chemical classes correlated strongly with each other, strengthening the notion that certain biochemical processes can be monitored. For example, a series of fatty acids was found to be increased after salbutamol intake, suggesting lipolysis stimulation. Peaks corresponding to salbutamol, its main metabolite salbutamol-4-O-sulfate and formoterol were found to be generally increased in patients inhaling the drugs on an as-needed basis, as compared to non-medicated volunteers. Overall, these results suggest such real-time breath analysis is a useful tool for non-invasive therapeutic drug monitoring
Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis
On-Line Analysis of Exhaled Breath Focus Review
On-line analysis of exhaled breath offers insight into a person's metabolism without the need for sample preparation or sample collection. Due to its noninvasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential. The unique features of this technology make it an attractive candidate for applications in medicine, beyond the task of diagnosis. We review the current methodologies for on-line breath analysis, discuss current and future applications, and critically evaluate challenges and pitfalls such as the need for standardization. Special emphasis is given to the use of the technology in diagnosing respiratory diseases, potential niche applications, and the promise of breath analysis for personalized medicine. The analytical methodologies used range from very small and low-cost chemical sensors, which are ideal for continuous monitoring of disease status, to optical spectroscopy and state-of-the-art, high-resolution mass spectrometry. The latter can be utilized for untargeted analysis of exhaled breath, with the capability to identify hitherto unknown molecules. The interpretation of the resulting big data sets is complex and often constrained due to a limited number of participants. Even larger data sets will be needed for assessing reproducibility and for validation of biomarker candidates. In addition, molecular structures and quantification of compounds are generally not easily available from on-line measurements and require complementary measurements, for example, a separation method coupled to mass spectrometry. Furthermore, a lack of standardization still hampers the application of the technique to screen larger cohorts of patients. This review summarizes the present status and continuous improvements of the principal on-line breath analysis methods and evaluates obstacles for their wider application
Detection of Volatile Organic Compounds with Secondary Electrospray Ionization and Proton Transfer Reaction High-Resolution Mass Spectrometry: A Feature Comparison
The analysis of volatiles is of high relevance for a wide range of applications from environmental air sampling and security screening to potential medical applications. High-resolution mass spectrometry methods offer a particularly wide compound coverage, sensitivity, and selectivity. Online approaches allow direct analysis in real time without the need for sample preparation. For the first time, we systematically compared the analysis of volatile organic compounds with secondary electrospray ionization (SESI) and proton transfer reaction (PTR) high-resolution mass spectrometry. The selected instruments had comparable mass resolving powers with m/Delta m >= 15000, which is particularly suitable for nontargeted analysis, for example, of exhaled breath. Exhalations from 14 healthy adults were analyzed simultaneously on both instruments. In addition, 97 reference standards from nine chemical classes were analyzed with a liquid evaporation system. Surprisingly, in breath, we found more complementary than overlapping features. A clear mass dependence was observed for each method with the highest number of detected m/z features for SESI in the high mass region (m/z = 150-250) and for PTR in the low mass region (m/z = 50-150). SESI yielded a significantly higher numbers of peaks (828) compared to PTR (491) among a total of 1304 unique breath m/z features. The number of signals observed by both methods was lower than expected (133 features) with 797 unique SESI features and 374 unique PTR features. Hypotheses to explain the observed mass-dependent differences are proposed
Legislative Documents
Also, variously referred to as: Senate bills; Senate documents; Senate legislative documents; legislative documents; and General Court documents