Gauging circadian variation in ketamine metabolism by real-time breath analysis

The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism

Ion mobility spectrometry coupled to laser-induced fluorescence for probing the electronic structure and conformation of gas-phase ions

We report on an improved design of a differential ion mobility analyzer (DMA) coupled to laser-induced fluorescence (LIF) for the simultaneous retrieval of two-dimensional information on the electric mobility and fluorescence spectroscopy of gas-phase ions. This enhanced design includes an ion funnel inter-face at the input orifice of the DMA and a nozzle beam stage at the output of the DMA. These improvements allow the detection of fluorescence not only from pure dyes and their clusters, as was demonstrated recently, but also from fluorophore-tagged biomolecules. Complex mixtures of fluorescent compounds can be separated by the DMA and studied by LIF. This unique combination of instruments also provides a powerful platform for probing fluorescent proteins in the gas phase. The green fluorescent protein (GFP) was tested on a new setup. In contrast to high vacuum, where no GFP fluorescence was detected, the presence of a LIF signal at the output of the DMA could explain some specific fluorescent properties of GFP in the gas phase. Given that both conformation and fluorescence are key properties of biological molecules in the gas phase, we expect that our enhanced design will answer the question whether gas-phase proteins retain their liquid-phase native structure or not

Gauging circadian variation in ketamine metabolism by real-time breath analysis

The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism

Secondary electrospray ionization-mass spectrometry and a novel statistical bioinformatic approach identifies a cancer-related profile in exhaled breath of breast cancer patients: a pilot study

Breath analysis represents a new frontier in medical diagnosis and a powerful tool for cancer biomarker discovery due to the recent development of analytical platforms for the detection and identification of human exhaled volatile compounds. Statistical and bioinformatic tools may represent an effective complement to the technical and instrumental enhancements needed to fully exploit clinical applications of breath analysis. Our exploratory study in a cohort of 14 breast cancer patients and 11 healthy volunteers used secondary electrospray ionization-mass spectrometry (SESI-MS) to detect a cancer-related volatile profile. SESI-MS full-scan spectra were acquired in a range of 40-350 mass-to-charge ratio (m/z), converted to matrix data and analyzed using a procedure integrating data pre-processing for quality control, and a two-step class prediction based on machine-learning techniques, including a robust feature selection, and a classifier development with internal validation. MS spectra from exhaled breath showed an individual-specific breath profile and high reciprocal homogeneity among samples, with strong agreement among technical replicates, suggesting a robust responsiveness of SESI-MS. Supervised analysis of breath data identified a support vector machine (SVM) model including 8 features corresponding to m/z 106, 126, 147, 78, 148, 52, 128, 315 and able to discriminate exhaled breath from breast cancer patients from that of healthy individuals, with sensitivity and specificity above 0.9.Our data highlight the significance of SESI-MS as an analytical technique for clinical studies of breath analysis and provide evidence that our noninvasive strategy detects volatile signatures that may support existing technologies to diagnose breast cancer

Supplementary Material for: Breath Analysis in Real Time by Mass Spectrometry in Chronic Obstructive Pulmonary Disease

<b><i>Background:</i></b> It has been suggested that exhaled breath contains relevant information on health status. <b><i>Objectives:</i></b> We hypothesized that a novel mass spectrometry (MS) technique to analyze breath in real time could be useful to differentiate breathprints from chronic obstructive pulmonary disease (COPD) patients and controls (smokers and nonsmokers). <b><i>Methods:</i></b> We studied 61 participants including 25 COPD patients [Global Initiative for Obstructive Lung Disease (GOLD) stages I-IV], 25 nonsmoking controls and 11 smoking controls. We analyzed their breath by MS in real time. Raw mass spectra were then processed and statistically analyzed. <b><i>Results:</i></b> A panel of discriminating mass-spectral features was identified for COPD (all stages; n = 25) versus healthy nonsmokers (n = 25), COPD (all stages; n = 25) versus healthy smokers (n = 11) and mild COPD (GOLD stages I/II; n = 13) versus severe COPD (GOLD stages III/IV; n = 12). A blind classification (i.e. leave-one-out cross validation) resulted in 96% sensitivity and 72.7% specificity (COPD vs. smoking controls), 88% sensitivity and 92% specificity (COPD vs. nonsmoking controls) and 92.3% sensitivity and 83.3% specificity (GOLD I/II vs. GOLD III/IV). Acetone and indole were identified as two of the discriminating exhaled molecules. <b><i>Conclusions:</i></b> We conclude that real-time MS may be a useful technique to analyze and characterize the metabolome of exhaled breath. The acquisition of breathprints in a rapid manner may be valuable to support COPD diagnosis and to gain insight into the disease