Rapid and simple LC-MS/MS-Screening of 64 novel psychoactive substances using dried blood spots

The range of novel psychoactive substances (NPS) including phenethylamines, cathinones, piperazines, tryptamines, etc. is continuously growing. Therefore, fast and reliable screening methods for these compounds are essential and needed. The use of dried blood spots (DBS) for a fast straightforward approach helps to simplify and shorten sample preparation significantly. DBS were produced from 10 µl of whole blood and extracted offline with 500 µl methanol followed by evaporation and reconstitution in mobile phase. Reversed-phase chromatographic separation and mass spectrometric detection (RP-LC-MS/MS) was achieved within a run time of 10 min. The screening method was validated by evaluating the following parameters: limit of detection (LOD), matrix effect, selectivity and specificity, extraction efficiency, and short-term and long-term stability. Furthermore, the method was applied to authentic samples and results were compared with those obtained with a validated whole blood method used for Routine analysis of NPS. LOD was between 1 and 10 ng/ml. No interference from Matrix compounds was observed. The method was proven to be specific and selective for the analytes, although with limitations for 3-FMC/flephedrone and MDDMA/MDEA. Mean extraction efficiency was 84.6 %. All substances were stable in DBS for at least a week when cooled. Cooling was essential for the stability of cathinones. Prepared samples were stable for at least 3 days. Comparison to the validated whole blood method yielded similar results. DBS were shown to be useful in developing a rapid screening method for NPS with simplified sample preparation. Copyright © 2013 John Wiley & Sons, Ltd

Temporal variations of perfluoroalkyl substances and polybrominated diphenyl ethers in alpine snow

The occurrence and temporal variation of 18 perfluoroalkyl substances (PFASs) and 8 polybrominated diphenyl ethers (PBDEs) in the European Alps was investigated in a 10 m shallow firn core from Colle Gnifetti in the Monte Rosa Massif (4455 m above sea level). The firn core encompasses the years 1997-2007. Firn core sections were analyzed by liquid chromatography-tandem mass spectrometry (PFASs) and gas chromatography-mass spectrometry (PBDEs). We detected 12 PFASs and 8 PBDEs in the firn samples. Perfluorobutanoic acid (PFBA; 0.3-1.8 ng L(-1)) and perfluorooctanoic acid (PFOA; 0.2-0.6 ng L(-1)) were the major PFASs while BDE 99 (

Optional course "Homeopathically potentised substances: placebos or effective?" for medical students at the University of Bern, Switzerland

Background Apart from compulsory lectures on classical homeopathy (CH), traditional Chinese medicine/acupuncture, neural therapy and anthroposophically extended medicine (AEM), our institute at the University of Bern offers several optional practical courses for medical students. The aim of this course during autumn 2011 and spring 2012 was to discuss basic research, observational and clinical studies in the fields of CH and AEM, so that students i) learned how to read and appraise scientific publications, ii) learned how complementary medicine can be investigated with scientific methods, and iii) were able to form their own opinion about the possible specific effects and effectiveness of homeopathically potentised substances. Methods Introductory lectures on AEM, CH and study design were given to 12 second year medical students. The students appraised 12 research articles and presented the results in class, followed by discussions with experts in the fields of basic and clinical research from our institute. A company producing homeopathic remedies was visited and students could practise potentization procedures and trituration. At the end of the course, students compiled posters with arguments in favour of and against specific effects and effectiveness as well as their own conclusions. The course was evaluated using a written questionnaire with closed and open questions. Results Previous knowledge about CH and AEM was scarce among the students. It slightly increased during the course, and the course itself fostered their interest on the topic. This course was chosen by most students, because they were genuinely interested in the topic (and not because other courses they had wanted to visit were fully booked). The students especially valued the discussions, the various perspectives presented to them, and experiencing a potentization process. Conclusion Medical students were interested to learn more about homeopathically potentised substances. The contradictory study results made it difficult for them to form their own opinion. Apart from appraising articles, the students would have liked to meet and talk to patients.

Environmental Effects and Aquatic Organisms: Investigations of Molecular Mechanisms of Carcinogenesis

Cancers of the reproductive system are among the leading causes of mortality in women in the United States. While both genetic and environmental factors have been implicated in their etiology, the extent of the contribution of environmental factors to human diseases remains controversial. To better address the role of environmental exposures in cancer etiology, there has been an increasing focus on the development of nontraditional, environmentally relevant models. Our research involves the development of one such model, Gonadal tumors have been described in the softshell clam (Mya arenaria) in Maine and the hardshell clam (Mercenaria spp.) from Florida. Prevalence of these tumors is as high as 40% in some populations in eastern Maine and 60% in Some areas along the Indian River in Florida. The average tumor prevalence in Maine and Florida is approximately 20 and 11%, respectively. An association has been suggested between the use of herbicides and the incidence of gonadal tumors in the softshell clam in Maine. The role of environmental exposures in the development of the tumors in Mercenaria in Florida is unknown, however, there is evidence that genetic factors may contribute to its etiology. Epidemiologic studies of human populations in these same areas show a higher than average mortality rate due to cancers of the reproductive system in women, including both ovarian and breast career. The relationship, if any, among these observations is unknown, Our studies on the molecular basis of this disease in clams may provide additional information on environmental exposures and their possible link to cancer in clams and other organisms, including humans.

Sustainable Wastewater Management: Is it Possible to Regulate Micropollution in the Future by Learning from the Past? A Policy Analysis

This paper applies a policy analysis approach to the question of how to effectively regulate micropollution in a sustainable manner. Micropollution is a complex policy problem characterized by a huge number and diversity of chemical substances, as well as various entry paths into the aquatic environment. It challenges traditional water quality management by calling for new technologies in wastewater treatment and behavioral changes in industry, agriculture and civil society. In light of such challenges, the question arises as to how to regulate such a complex phenomenon to ensure water quality is maintained in the future? What can we learn from past experiences in water quality regulation? To answer these questions, policy analysis strongly focuses on the design and choice of policy instruments and the mix of such measures. In this paper, we review instruments commonly used in past water quality regulation. We evaluate their ability to respond to the characteristics of a more recent water quality problem, i.e., micropollution, in a sustainable way. This way, we develop a new framework that integrates both the problem dimension (i.e., causes and effects of a problem) as well as the sustainability dimension (e.g., long-term, cross-sectoral and multi-level) to assess which policy instruments are best suited to regulate micropollution. We thus conclude that sustainability criteria help to identify an appropriate instrument mix of end-of-pipe and source-directed measures to reduce aquatic micropollution.

Assessing the impact of multiple stressors on aquatic biota: the receptor's side matters.

Aquatic ecosystems are confronted with multiple stress factors. Current approaches to assess the risk of anthropogenic stressors to aquatic ecosystems are developed for single stressors and determine stressor effects primarily as a function of stressor properties. The cumulative impact of several stressors, however, may differ markedly from the impact of the single stressors and can result in nonlinear effects and ecological surprises. To meet the challenge of diagnosing and predicting multiple stressor impacts, assessment strategies should focus on properties of the biological receptors rather than on stressor properties. This change of paradigm is required because (i) multiple stressors affect multiple biological targets at multiple organizational levels, (ii) biological receptors differ in their sensitivities, vulnerabilities, and response dynamics to the individual stressors, and (iii) biological receptors function as networks, so that actions of stressors at disparate sites within the network can lead via indirect or cascading effects, to unexpected outcomes.

Optimizing the aquatic toxicity assessment under REACH through an integrated testing strategy (ITS).

To satisfy REACH requirements a high number of data on chemical of interest should be supplied to the European Chemicals Agency. To organize the various kinds of information and help the registrants to choose the best strategy to obtain the needed information limiting at the minimum the use of animal testing, integrated testing strategies (ITSs) schemes can be used. The present work deals with regulatory data requirements for assessing the hazards of chemicals to the aquatic pelagic environment. We present an ITS scheme for organizing and using the complex existing data available for aquatic toxicity assessment. An ITS to optimize the choice of the correct prediction strategy for aquatic pelagic toxicity is described. All existing information (like physico-chemical information), and all the alternative methods (like in silico, in vitro or the acute-to-chronic ratio) are considered. Moreover the weight of evidence approach to combine the available data is included.

Universal ontology: attentive tracking of objects and substances across languages and over development

Previous research has demonstrated that adults are successful at visually tracking rigidly moving items, but experience great difficulties when tracking substance-like ‘‘pouring’’ items. Using a comparative approach, we investigated whether the presence/absence of the grammatical count–mass distinction influences adults and children’s ability to attentively track objects versus substances. More specifically, we aimed to explore whether the higher success at tracking rigid over substance-like items appears universally or whether speakers of classifier languages (like Japanese, not marking the object–substance distinction) are advantaged at tracking substances as compared to speakers of non-classifier languages (like Swiss German, marking the object–substance distinction). Our results supported the idea that language has no effect on low-level cognitive processes such as the attentive visual processing of objects and substances. We concluded arguing that the tendency to prioritize objects is universal and independent of specific characteristics of the language spoken.

Hormone als Schadstoffe?

Endokrine Disruptoren sind Umweltsubstanzen, die in das Hormonsystem von Organismen eingreifen, und dadurch zu schädlichen Wirkungen führen. Sie entfalten ihre Wirkung entweder, indem sie den Hormonstoffwechsel stören oder indem sie die Wirkung von Hormonen imitieren. Eine wichtige Gruppe von endokrinen Disruptoren in der aquatischen Umwelt sind Stoffe, die an Östrogenrezeptoren binden und dadurch wie das weibliche Sexualhormon, 17β-Östradiol wirken. Zu den Umweltöstrogenen gehören sowohl synthetische Chemikalien wie auch natürliche Substanzen. Sowohl Laborversuche wie Felduntersuchungen an Fischen haben gezeigt, dass bereits sehr niedrige Konzentrationen von Umweltöstrogenen in Gewässern in der Lage sind, Störungen des Hormonsystems auszulösen. Environmental estrogens Endocrine disrupters are environmental substances which interfere with the hormone system of organisms and thereby induce adverse effects. They exert their biological activity either by disrupting hormone metabolism or by imitating the biological action of the endogenous hormones. In the aquatic environment, an important group of endocrine disrupters is represented by the estrogen-active compounds, which mimic the female sex hormone, 17β-estradiol. Both laboratory experiments and field studies on fishes have demonstrated that already very low concentrations of environmental estrogens are able to induce disturbances in the hormone system and hormone-regulated processes of fishes.

Detection and quantification of 56 new psychoactive substances in whole blood and urine by LC-MS/MS

BACKGROUND New psychoactive substances (NPS) have become increasingly prevalent and are sold in internet shops as 'bath salts' or 'research chemicals' and comprehensive bioanalytical methods are needed for their detection. METHODOLOGY We developed and validated a method using LC and MS/MS to quantify 56 NPS in blood and urine, including amphetamine derivatives, 2C compounds, aminoindanes, cathinones, piperazines, tryptamines, dissociatives and others. Instrumentation included a Synergi Polar-RP column (Phenomenex) and a 3200 QTrap mass spectrometer (AB Sciex). Run time was 20 min. CONCLUSION A novel method is presented for the unambiguous identification and quantification of 56 NPS in blood and urine samples in clinical and forensic cases, e.g., intoxications or driving under the influence of drugs.

Newly detected ozone-depleting substances in the atmosphere

Ozone-depleting substances emitted through human activitiescause large-scale damage to the stratospheric ozone layer, and influence global climate. Consequently, the production of many of these substances has been phased out; prominent examples are the chlorofluorocarbons (CFCs), and their intermediate replacements, the hydrochlorofluorocarbons (HCFCs). So far, seven types of CFC and six types of HCFC have been shown to contribute to stratospheric ozone destruction 1,2. Here, we report the detection and quantification of a further three CFCs and one HCFC. We analysed the composition of unpolluted air samples collected in Tasmania between 1978 and 2012, and extracted from deep firn snow in Greenland in 2008, using gas chromatography with mass spectrometric detection. Using the firn data, we show that all four compounds started to emerge in the atmosphere in the 1960s. Two of the compounds continue to accumulate in the atmosphere. We estimate that, before 2012, emissions of all four compounds combined amounted to more than 74,000 tonnes. This is small compared with peak emissions of other CFCs in the 1980s of more than one million tonnes each year 2. However, the reported emissions are clearly contrary to the intentions behind the Montreal Protocol, and raise questions about the sources of these gases.

Seasonal variation of high-molecular-weight compounds in the water-soluble fraction of organic urban aerosols

Aerosol samples were collected in Zurich, Switzerland, at an urban background site and were analyzed with size exclusion chromatography (SEC) and laser/desorption ionization mass spectrometry (LDI-MS) for water-soluble organic compounds with high molecular weight. Daily samples were collected during two campaigns in winter and summer, for 1 month each. The concentration of high-molecular-weight compounds (humic-like substances (HULIS)) was between 0.4 and 4 μg/m3 in winter and summer. The most intense signals in the LDI-MS mass spectra were measured between m/z150 and 500, comparing well with the mode of the two main high mass peaks determined with SEC corresponding to masses between 200 and 600 Da. For the maximum molecular weight, however, different results were obtained by the two techniques: whereas a maximum molecular weight between 1300 and 3300 Da was found with SEC, hardly any peaks above m/z700 were measured with LDI-MS. During summer the maximum molecular weight of HULIS (determined with SEC) correlates positively with several parameters such as ozone and increased temperature indicative of enhanced atmospheric photo-oxidation. The HULIS concentration also correlates positively with the oxalic acid concentration in the particles. This suggests that HULIS are generated by secondary processes in summer. The lack of such correlations during winter suggests that other sources and processes might be important during colder seasons.

Analyses of the Erosive Effect of Dietary Substances and Medications on Deciduous Teeth.

This study aimed at analysing the erosive potential of 30 substances (drinks, candies, and medicaments) on deciduous enamel, and analyse the associated chemical factors with enamel dissolution. We analysed the initial pH, titratable acidity (TA) to pH 5.5, calcium (Ca), inorganic phosphate (Pi), and fluoride (F) concentration, and degree of saturation ((pK -pI)HAP, (pK -pI)FAP, and (pK-pI)CaF2) of all substances. Then, we randomly distributed 300 specimens of human deciduous enamel into 30 groups (n = 10 for each of the substances tested. We also prepared 20 specimens of permanent enamel for the sake of comparison between the two types of teeth, and we tested them in mineral water and Coca-Cola®. In all specimens, we measured surface hardness (VHN: Vickers hardness numbers) and surface reflection intensity (SRI) at baseline (SHbaseline and SRIbaseline), after a total of 2 min (SH2min) and after 4 min (SH4min and SRI4min) erosive challenges (60 ml of substance for 6 enamel samples; 30°C, under constant agitation at 95 rpm). There was no significant difference in SHbaseline between deciduous and permanent enamel. Comparing both teeth, we observed that after the first erosive challenge with Coca-Cola®, a significantly greater hardness loss was seen in deciduous (-90.2±11.3 VHN) than in permanent enamel (-44.3±12.2 VHN; p = 0.007), but no differences between the two types of teeth were observed after two challenges (SH4min). After both erosive challenges, all substances except for mineral water caused a significant loss in relative surface reflectivity intensity, and most substances caused a significant loss in surface hardness. Multiple regression analyses showed that pH, TA and Ca concentration play a significant role in initial erosion of deciduous enamel. We conclude that drinks, foodstuffs and medications commonly consumed by children can cause erosion of deciduous teeth and erosion is mainly associated with pH, titratable acidity and calcium concentration in the solution.