Christian Berchtold

On the mechanism of extractive electrospray ionization.

Extractive electrospray ionization (EESI) is a powerful ambient ionization technique that can provide comprehensive mass spectrometric (MS) information on aerosols, complex liquids, or suspensions without any sample pretreatment. An understanding of the EESI mechanism is critical for defining its range of application, the advantages, and limitations of EESI, and for improving its repeatability, sensitivity, and selectivity. However, no systematic study of EESI mechanisms has been conducted so far. In this work, fluorescence studies in the EESI plume using rhodamine 6G and H-acid sodium salt directly demonstrate that liquid-phase interactions occur between charged ESI droplets and neutral sample droplets. Moreover, the effect of the composition of the primary ESI spray and sample spray on signals of the analyte in EESI-MS was investigated systematically. The results show that the analyte signals strongly depend on its solubility in the solvents involved, indicating that selective extraction is the dominant mechanism involved in the EESI process. This mechanistic study provides valuable insights for optimizing the performance of EESI in future applications.

Rapid fingerprinting and classification of extra virgin olive oil by microjet sampling and extractive electrospray ionization mass spectrometry

Microjet sampling in combination with extractive electrospray ionization (EESI) mass spectrometry (MS) was applied to the rapid characterization and classification of extra virgin olive oil (EVOO) without any sample pretreatment. When modifying the composition of the primary ESI spray solvent, mass spectra of an identical EVOO sample showed differences. This demonstrates the capability of this technique to extract molecules with varying polarities, hence generating rich molecular information of the EVOO. Moreover, with the aid of microjet sampling, compounds of different volatilities (e.g.E-2-hexenal, trans-trans-2,4-heptadienal, tyrosol and caffeic acid) could be sampled simultaneously. EVOO data was also compared with that of other edible oils. Principal Component Analysis (PCA) was performed to discriminate EVOO and EVOO adulterated with edible oils. Microjet sampling EESI-MS was found to be a simple, rapid (less than 2 min analysis time per sample) and powerful method to obtain MS fingerprints of EVOO without requiring any complicated sample pretreatment steps.

Real-time monitoring of exhaled drugs by mass spectrometry

Future individualized patient treatment will need tools to monitor the dose and effects of administrated drugs. Mass spectrometry may become the method of choice to monitor drugs in real time by analyzing exhaled breath. This review describes the monitoring of exhaled drugs in real time by mass spectrometry. The biological background as well as the relevant physical properties of exhaled drugs are delineated. The feasibility of detecting and monitoring exhaled drugs is discussed in several examples. The mass spectrometric tools that are currently available to analyze breath in real time are reviewed. The technical needs and state of the art for on-site measurements by mass spectrometry are also discussed in detail. Off-line methods, which give support and are an important source of information for real-time measurements, are also discussed. Finally, some examples of drugs that have already been successfully detected in exhaled breath, including propofol, fentanyl, methadone, nicotine, and valproic acid are presented. Real-time monitoring of exhaled drugs by mass spectrometry is a relatively new field, which is still in the early stages of development. New technologies promise substantial benefit for future patient monitoring and treatment.

Extractive Electrospray Ionization Mass Spectrometry—Enhanced Sensitivity Using an Ion Funnel

Electrodynamic ion funnel interfaces for electrospray ionization (ESI) have shown to enhance the sensitivity of measurements by more than 2 orders of magnitude in the intermediate pressure region of the instrument (1-30 Torr). In this study, we use an ion funnel at ambient pressure to enhance the sensitivity of extractive electrospray ionization (EESI) by spraying directly into the ion funnel. EESI is a powerful ionization technique that is capable of handling complex matrixes that may contain dozens of compounds. Our results using atenolol, salbutamol, and cocaine as test compounds show that we can improve the limit of detection for these compounds by more than 3 orders of magnitude compared to standard EESI experiments.

Breath analysis in real time by mass spectrometry in chronic obstructive pulmonary disease.

Background: It has been suggested that exhaled breath contains relevant information on health status. Objectives: 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). Methods: 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. Results: 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. Conclusions: 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.

Direct detection of chlorpropham on potato skin using desorption electrospray ionization

Most pesticides, herbicides and other plant treatment agents are applied to the crop surface. Direct mass spectrometric methods, such as desorption electrospray ionization (DESI), offer new ways to analyze plant samples directly and rapidly. A strategy for the development and optimization of a DESI method for the direct determination of chemicals on complex surfaces is described. Chlorpropham (CP) was applied to potato surfaces as an example for a crop protection agent and analyzed using a self-made DESI source. Aspects such as instrument selectivity, sensitivity and reproducibility were investigated. The MS(4) fragmentation pattern of CP was analyzed to achieve the necessary detection selectivity, and is discussed in detail. Similar fragmentation was found in the ESI and DESI mass spectra, indicating that the mechanisms of ESI and DESI are closely related. A DESI method for semi-quantification of CP on potatoes was developed. Detection limits of 6.5 µg/kg were found using MS/MS. The reproducibility, in the range of 12% (signal variation), appears to be sufficient for semi-quantitative measurements.

A new strategy based on real-time secondary electrospray ionization and high-resolution mass spectrometry to discriminate endogenous and exogenous compounds in exhaled breath

Breath is considered to be an easily accessible matrix, whose chemical composition relates to compounds present in blood. Therefore many metabolites are expected in exhaled breath, which may be used in the future for the development of diagnostic methods. In this article, a new strategy to discriminate between exhaled endogenous metabolites and exhaled exogenous contaminants by direct high-resolution mass spectrometry is introduced. The analysis of breath in real-time by secondary electrospray ionization mass spectrometry allows to interpret the origin of exhaled compounds. Exhaled metabolites that originate in the respiratory system show reproducible and significant patterns if plotted in real-time (>1 data point per second). An exhaled metabolite shows a signal that tends to rise at the end of a complete (forced) exhalation. In contrast, exogenous compounds, which may be present in room air, are gradually diluted by the air from the deeper lung and therefore show a trend of falling intensity. Signals found in breath by using this pattern recognition are linked to potential metabolites by comparison with online databases. In addition to this real-time approach, it is also shown how to combine this method with classical analytical methods in order to potentially identify unknown metabolites. Finally exhaled compounds following smoking a cigarette, chewing gum, or drinking coffee were investigated to underline the usefulness of this new approach.

Sensitive detection of drug vapors using an ion funnel interface for secondary electrospray ionization mass spectrometry

In this study, we use an ion funnel (IF) at ambient pressure to enhance the sensitivity of secondary electrospray ionization (SESI). Atenolol, salbutamol and cocaine as test compounds are delivered to the SESI interface in the gas phase and are charged with three nano electrosprays. In our experiments, we show that the compounds can be detected at concentrations in the low pptv range, which is an increase of two orders of magnitude compared with the results without the IF. With a standard SESI interface, the compounds could not be detected at all. With the use of the SESI IF interface for the headspace analysis of bananas and limes, we can detect many more compounds and at higher intensities than with a standard SESI interface.

Contribution of liquid-phase and gas-phase ionization in extractive electrospray ionization mass spectrometry of primary amines.

In this study, we investigated how binary mixtures of compounds influence each others signal intensity in electrospray ionization (ESI), extractive electrospray ionization (EESI) and secondary electrospray ionization (SESI) experiments. The experiments were conducted using a series of homologous primary amines (from 1-butyl to 1-decylamine). In every experiment, two of the amines were present, and all 21 possible combinations were measured with EESI, ESI and SESI as ionization sources. Except for the volatility, which decreases with increasing molecular weight, the physico–chemical properties of the amines are very similar, so that the intensity ratio obtained in each experiment provides information about discrimination effects occurring during the ionization process. The results show that for the relatively volatile compounds investigated, the EESI ionization mechanism resembles the SESI-like gas-phase charge transfer more than ESI-like analyte ionization in solution. In addition, almost no discrimination effects were observed in the spectra obtained in EESI experiments. Quantitative EESI experiments with nonylamine as internal standard showed that EESI is capable of providing both more accurate and more precise results than SESI and ESI.

High mass resolution breath analysis using secondary electrospray ionization mass spectrometry assisted by an ion funnel

In this study, we used secondary electrospray ionization mass spectrometry assisted by an ion funnel (IF) operating at ambient pressure to find compounds in the mass range of 100-500 m/z in online breath fingerprinting experiments. In low-resolution experiments conducted on an ion trap instrument, we found that pyridine is present in breath of individuals long after drinking coffee. In high-resolution experiments conducted on a Fourier transform ion cyclotron resonance, we found more than 30 compounds in the mass range of 100-500 m/z in analogous online breath experiments. More than a third of these compounds have molecular weights above 200 Daltons and have not been mentioned in previous studies. In low-resolution experiments as well as experiments without the IF, these compounds could not be detected.