Sensitivity improvement in hydrophilic interaction chromatography negative mode electrospray ionization mass spectrometry using 2-(2-methoxyethoxy)ethanol as a post-column modifier for non-targeted metabolomics
Koch W.,Helmholtz Center Munich |
Koch W.,TU Munich |
Koch W.,German Center for Diabetes |
Forcisi S.,Helmholtz Center Munich |
And 8 more authors.
Journal of Chromatography A | Year: 2014
The application of ammonia acetate buffered liquid chromatography (LC) eluents is known to concomitantly lead to ion suppression when electrospray ionization mass spectrometry (ESI-MS) detection is used. In negative ESI mode, post column infusion of 2-(2-methoxyethoxy)ethanol (2-MEE) was shown in the literature to help to compensate this adverse effect occurring in reversed phase liquid chromatography mass spectrometry (RP-LC-MS) analyses. Here a setup of direct infusion and hydrophilic interaction chromatography (HILIC) post-column infusion experiments was established in order to investigate systematically the beneficial effects of 2-MEE. We demonstrate that, 2-MEE can help to improve ESI-MS sensitivity in HILIC too and reveal analyte structure specific behaviors. Our study indicates that 2-MEE especially improves ESI response for small and polar molecules. The ESI response of stable isotope labeled amino acids spiked into biological matrices increases up to 50-fold (i.e. D5-l-glutamic acid) when post column infusion of 2-MEE is applied. A non-targeted analysis of a pooled urine sample via HILIC-ESI-QTOF-MS supports this hypothesis. In direct infusion, the combined application of an ammonia acetate buffered solution together with 2-MEE results in an improved ESI response compared to a non-buffered solution. We observed up to 60-fold increased ESI response of l-lysine. We propose this effect is putatively caused by the formation of smaller ESI droplets and stripping of positive charge from ESI droplets due to evaporation of acetic acid anions. In summary, post-column infusion of 2-MEE especially enhances ESI response of small and polar molecules. Therefore it can be regarded as a valuable add-on in targeted or non-targeted metabolomic HILIC-MS studies since this method sets a focus on this molecule category. © 2014 Elsevier B.V. Source
Sampsonidis I.,Aristotle University of Thessaloniki |
Sampsonidis I.,University of Glasgow |
Witting M.,Helmholtz Center Munich |
Koch W.,Helmholtz Center Munich |
And 7 more authors.
Journal of Chromatography A | Year: 2015
In the present work two different approaches, a semi-quantitative and a Derringer function approach, were developed to assist column selection for method development in targeted metabolomics. These approaches were applied in the performance assessment of three HILIC columns with different chemistries (an amide, a diol and a zwitterionic phase). This was the first step for the development of a HILIC UPLC-MS/MS method that should be capable to analyze a large number of polar metabolites. Two gradient elution profiles and two mobile phase pH values were tested for the analysis of multi-analyte mixtures. Acquired chromatographic data were firstly treated by a ratiometric, "semi-quantitative" approach which quantifies various overall analysis parameters (e.g. the percent of detected compounds, retentivity and resolved critical pairs). These parameters were used to assess chromatographic performance in a rather conventional/traditional and cumbersome/labor-intensive way. Secondly, a comprehensive and automated comparison of the three columns was performed by monitoring several well-known chromatographic parameters (peak width, resolution, tailing factor, etc.) using a lab-built programming script which calculates overall desirability utilizing Derringer functions. Derringer functions exhibit the advantage that column performance is ultimately expressed in an objective single and quantitative value which can be easily interpreted. In summary, results show that each column exhibits unique strengths in metabolic profiling of polar compounds. The applied methodology proved useful for the selection of the most effective chromatographic system during method development for LC-MS/MS targeted metabolomics, while it could further assist in the selection of chromatographic conditions for the development of multi-analyte methods. © 2015 Elsevier B.V. Source
« Civil Maps debuts augmented reality maps for self-driving cars | Main | KLM to operate biofuel flights out of Los Angeles » Exposure to air pollution increases the risk of developing insulin resistance as a pre-diabetic state of type 2 diabetes, according to a new study by scientists of Helmholtz Zentrum München, in collaboration with colleagues of the German Center for Diabetes Research (DZD). The researchers reported these results in the journal Diabetes. Whether diabetes becomes manifest and when this occurs is not only due to lifestyle or genetic factors, but also due to traffic-related air pollution, said Professor Annette Peters, director of the Institute of Epidemiology II at Helmholtz Zentrum München and head of the research area of epidemiology of the DZD. For the current study, the team analyzed the data of 2,944 participants of the KORA (Cooperative Health Research in the Region Augsburg) F4 study conducted in southern Germany (2006-2008). They analyzed associations between individual air pollution concentration estimated by land use regression and HOMA-IR (homeostasis model assessment-estimated insulin resistance), glucose, insulin, HbA (glycated hemoglobin), leptin, and hs-CRP (high-sensitivity C-reactive protein) from fasting samples using multivariable linear regression models. Effect estimates were calculated for the whole study population and subgroups of non-diabetic, pre-diabetic and diabetic individuals. Among all participants, a 7.9μg/m3 increment in particulate matter Nitrogen dioxide was associated with HOMA-IR, glucose, insulin, and leptin. Effect estimates for pre-diabetic individuals were much larger and highly statistically significant, while non-diabetic and diabetic individuals showed rather weak associations. No association was seen for HbA . The results revealed that people who already have an impaired glucose metabolism, so-called pre-diabetic individuals, are particularly vulnerable to the effects of air pollution. In these individuals, the association between increases in their blood marker levels and increases in air pollutant concentrations is particularly significant! Thus, over the long term—especially for people with impaired glucose metabolism—air pollution is a risk factor for type 2 diabetes. The authors are also concerned that the concentrations of air pollutants, though below EU threshold values, are still above the proposed guidelines of the World Health Organization (WHO). As a consequence, they demand changes in government policy. Moreover, the association between increased exposure to air pollution and respiratory and cardiovascular diseases has now been clearly established. Next, the scientists want to investigate the influence of ultrafine particles. A previous study of Helmholtz Zentrum München from 2013 showed that ultrafine particulate air pollution increases the risk of insulin resistance in childhood. In a meta-analysis from 2015 the same authors concluded that there is an association between long-term exposure to air pollutants and the development of type 2 diabetes.
News Article | September 13, 2016
A new study performed by researchers at Helmholtz Zentrum München, in collaboration with researchers at the German Center for Diabetes Research, has revealed that common levels of air pollution in homes notably increase the risk of developing insulin resistance as a pre-diabetic state of type 2 diabetes. What this means is that risk is strongly associated not just with “lifestyle” and genetics, but also with the environmental factors that most people have no control over, but which governments have the ability to regulate. Notably, the levels of air pollution observed in the study (in Germany) are well within European Union limits, but above those proposed by the World Health Organization (WHO). “Whether the disease becomes manifest and when this occurs is not only due to lifestyle or genetic factors, but also due to traffic-related air pollution,” commented Professor Annette Peters, director of the Institute of Epidemiology II at Helmholtz Zentrum München and head of the research area of epidemiology of the DZD. The press release continues, noting that, in collaboration with German Diabetes Center Düsseldorf and the German Heart Centre, the researchers “analyzed the data of nearly 3,000 participants of the KORA study who live in the city of Augsburg and two adjacent rural counties. All individuals were interviewed and physically examined. Furthermore, the researchers took fasting blood samples, in which they determined various markers for insulin resistance and inflammation. In addition, leptin was examined as adipokine which has been suggested to be associated with insulin resistance. Non-diabetic individuals underwent an oral glucose tolerance test to detect whether their glucose metabolism was impaired. The researchers compared these data with the concentrations of air pollutants at the place of residence of the participants, which they estimated using predictive models based on repeated measurements at 20 sites (for particle measurements) and at 40 sites (for nitrogen dioxide measurements) in the city and in the rural counties.” “The results revealed that people who already have an impaired glucose metabolism, so-called pre-diabetic individuals, are particularly vulnerable to the effects of air pollution,” stated Dr Kathrin Wolf, lead author of the new study. “In these individuals, the association between increases in their blood marker levels and increases in air pollutant concentrations is particularly significant! Thus, over the long term — especially for people with impaired glucose metabolism — air pollution is a risk factor for type 2 diabetes.” With regard to the implications of the findings, researcher Dr Alexandra Schneider, noted: “Lowering the threshold for acceptable air pollution levels would be a prudent step. We are all exposed to air pollution. An individual reduction by moving away from highly polluted areas is rarely an option.” The new findings are detailed in a paper published in the journal Diabetes. Drive an electric car? Complete one of our short surveys for our next electric car report. Keep up to date with all the hottest cleantech news by subscribing to our (free) cleantech newsletter, or keep an eye on sector-specific news by getting our (also free) solar energy newsletter, electric vehicle newsletter, or wind energy newsletter.