Projekte

FWF-Schrödinger project (Simone Braeuer)

Porcini mushrooms are amongst the most often collected and eaten wild mushrooms. Many people know about their value in the kitchen, but hardly anyone is aware that they can take up significant amounts of Hg and Se from the soil. While Se is an essential element for humans and can be beneficial to our health, Hg is a toxic heavy metal, and excessive consumption can pose a health risk to mushroom lovers.

Within this FWF-Schrödinger project, HPLC coupled to ICPMS will be used to determine the chemical forms in which Hg and Se are present in porcini mushrooms. The distribution of Hg and Se in porcini mushrooms will be investigated with laser ablation coupled to ICPMS in the A&MS group of Prof. Frank Vanhaecke, Ghent University, Belgium. Further, Hg isotope ratios will be determined in porcini mushrooms and the underlying soil with multi-collector ICPMS (also in the A&MS group).

The results will shed light on the uptake and fate of mercury in porcini mushrooms. Our findings will significantly contribute to our understanding of the cycling of mercury in the environment. The findings will also enable a better evaluation of the health risk arising from eating mercury-accumulating mushrooms.

Dissertation (Gerhard Goessler)

Government guidelines on the use of statistical methods in the field of pharmaceutical chemistry are often controversial. The goal of this work is to investigate some of the currently discussed topics by means of stochastic simulations (Monte-Carlo-methods) and also real datasets in order to identify weaknesses in the respective currently used statistical methods and to subsequently work out possible solutions.

Topics of interest are:

Shelf-Life-Determination: Estimating shelf-life for pharmaceutical products has long been a very controversial topic since the currently applied guideline (ICH Guideline Q1E6) has, from a statistical point of view, neither a sound scientific basis nor does it correspond to the respective goals of the ICH. The statistical approach proposed by the ICH is not suitable for estimating the shelf life with regard to total production, and a suitable criterion for the end of the shelf life with regard to total production is also not defined. Possible remedial measures might be the use of suitable linear mixed models, the use of quantile regression or the determination of tolerance intervals. Additionally, it has to be investigated (or agreed), which amount of the total production is allowed to be already out of specification at the end of the lifespan of a product – this in turn determines what has to be estimated (i.e. at which time a specific quantile of the distribution of the quality attribute is below/above the respective acceptance criterion).

Comparability of pharmaceutical products: (e.g. generic drug/originator), see for example the EMA Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development (2017). Due to several sources of variability (production, measurement errors, … ) it is not uncommon for the collected data to show a significant variability. Therefore, statistical methods are required for a proper comparison of these data. Unfortunately, it is not a trivial task to determine suitable criteria for this purpose (e.g. under which conditions can two drugs be considered pharmacologically equivalent with respect to a certain quality attribute) and to decide which statistical methods best meet the requirements that arise in this context. The goal of this work is to switch from a parameter-oriented approach (often focused solely on the mean) to one that focuses on the range of the distributions under consideration.

Validation of the linearity of analytical methods: The questions to be answered here are to what extent deviations can be tolerated and how to properly distinguish between statistical significance and practical relevance. Since there are no concrete governmental guidelines on how to deal with deviations, it has to be investigated how best to handle such an issue, e.g. it has to be clarified how the impact of a deviation should be assessed and how a reevaluation of the methods’ linearity should be carried out to show that the method is still in line with the intention of the guideline.

Dissolution Profile Comparison: The methods currently applied here have been the subject of critical discussions for many years. The best-known approach in this context is definitely the model-independent approach using f1(difference factor) and f2 (similarity factor), but there are also various other approaches, both model-dependent and model-independent. Therefore, it is difficult for those who have not had a thorough statistical training to develop a good understanding of the methods currently in use and to understand the ongoing scientific debate on this subject. Therefore, the aim of my work is here to analyze the current state of research on this topic and, if possible, to recommend improvements to the existing methods or even introduce a new one. Based on this work, the user should be provided with a methodology that can be viewed as "state of the art" and can be considered as “best practice” in dealing with this problem.

Master thesis (Patrick Miskulnig)

Heavy metals such as lead, chromium, cadmium, mercury and antimony are of great concern, as they can cause numerous health problems in humans exposed to high enough levels. These metals make their way into plastic products as catalysts during production or when recycled plastic is exposed to metals during the reclamation process. Plastics are often analysed by XRF, as it is a widely used non-destructive and fast technique to determine the elemental composition of various samples. The core task of this work is to test if XRF analysis is a reliable and quick alternative to traditional analytical methods. Therefore, ICPMS analysis on digested plastic samples will be applied to validate XRF data. Further side tasks will include the optimization of sample preparation procedures for ICPMS analysis. 

Dissertation (Martin Walenta)

Macro fungi are of special interest, as they are neither animals nor plants, which interact strongly with their environment (e.g. in symbiosis or as parasites). In addition, their role as protein suppliers for humans is becoming more and more important nowadays, as many people search for meatless alternatives, which in the case of fungi also contain little fat and a lot of water. Another interesting fact is that fungi have a very variable distribution of elements stored inside them and there are even some species which are considered as so-called hyperaccumulators.

In recent years, a lot of research has been done on how much and in what form arsenic is present in the various mushroom species. This is especially important, because the different chemical forms of arsenic differ greatly in their toxicity. In addition, it is important to know if the fungus absorbs the species directly as they are found in the environment or if the mushroom is able to metabolise them from other probably unknown species in soil for example. Based on these studies, it would be also important to know if other elements, such as Zn, Fe, Co or Se, show a similar behaviour to provide a better understanding of the metal metabolism of mushrooms.

Therefore, this PhD study is focused on the development of new methods to analyse different metal containing compounds in macro fungi, starting with the cultivation and collection of different types of mushrooms in various environments, to study the effect of different environments on the elemental distribution within the fungi. In the next steps, existing analysis methods need to be refined and new methods need to be developed to answer the question, in which form metals are present in the fungi and if these species are directly absorbed or metabolised within the mushroom. Furthermore, mushrooms accumulating specific metals should be identified and analysed to see if they could possibly used as fortified food or to purify polluted regions.

WTZ (Science & Technology cooperation), Albania

Numerous studies have demonstrated that ambient air pollution poses a potential hazard to the environment and human health. Especially particulate matter (PM), a complex mixture of very small particles and liquid droplets in the Earth’s atmosphere, is linked to a range of significant adverse health effects, including respiratory, chronic pulmonary and cardiovascular diseases. Therefore, the idea for the proposed project came from the common need to implement air quality friendly processes in all fields and to establish and improve methods to monitor air quality and to measure selected air pollutants in Albania. The integrated monitoring of air pollutants, in accordance with European Standards is an emergent need in Albania, since it’s a crucial prerequisite to Albania’s EU accession negotiations. Unfortunately, there is a critical lack on air quality data in Albania especially looking at heavy metals in particulate matter, although their determination is an important task for environmental researchers. Some heavy metals like cadmium (Cd), nickel (Ni) and chromium (Cr) or the metalloid arsenic (As) are classified as carcinogens.

The main goals of this project will be the following: (i) to strengthen the technical and scientific capacities of the Analytical Chemistry laboratory in the Department of Chemistry, FNS, University of Tirana aiming to expand its field of operation in air monitoring by implementing the latest techniques and experiences in the world. The gained experience will serve not only as a small scientific research center for the students doing the teaching and learning practices in this department, but also as an opportunity for other state institutes or private companies to collaborate in order to improve the quality of air in Albania; (ii) to gain new insights in the complex topic of particulate matter, leading to a new way of understanding the enrichment and behavior of given elements and pollutants in the atmosphere in the course of the year.

WTZ (Science & Technology cooperation), South Africa

Informal recycling of scrap metal and e-waste poses a risk for human health. An example of recycling of scrap metal is the casting of liquid aluminum from a collection of scrap metal into cooking pots. In a range of developing countries, artisanal (informal) aluminum cookware has replaced cast iron cookware. A study on locally manufactured artisanal aluminum cookware in Cameroon revealed that raw materials used included engine parts (from both cars and motorbikes), waste aluminum and e-waste (computer parts).The evaluated Pb exposure from the cookware revealed Pb exposure was as high as 260 μg per serving. A further study investigated the metal content in 42 locally made artisanal aluminum pots from 10 developing countries. The study revealed artisanal cookware as a potential multi-metal source with public health significance. Considering the possible metal exposure associated with artisanal cookware, there is a great need for a better understanding of the availability and risks to end users in order to develop risk mitigation guidelines.

In South Africa, artisanal aluminum pots have been in circulation for over two decades. Nonetheless, the locally available artisanal aluminum pots have not been investigated as a possible source of metal exposure. The characterization of metals in artisanal cookware and the identification of the deterioration of cookware products and mechanisms affecting them are critical to fully understanding the human health impact.

To determine the risk of metal exposure posed by artisanal cookware available in South Africa, our aims are

• To screen new and used artisanal cookware for metals with a focus on aluminum (Al), arsenic (As), cadmium (Cd) and lead (Pb)
• To quantify the level of metals in various leachate scenarios
• To determine the deterioration of artisanal cookware over time

Dissertation (Sieglinde Zelzer)

Vitamin D deficiency is a risk factor for the incidence and progression of a broad range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. Despite significant progress in the analysis of vitamin D metabolites and an expansion of our pathophysiological knowledge of vitamin D, the assessment of vitamin D status remains a challenging and partially unresolved issue. Scientific bodies around the globe recommend the measurement of 25-hydroxy vitamin D (25-OHD) in blood as the preferred test. However, growing evidence indicates significant limitations of this test, including analytical aspects and interpretation of results. More recent studies have suggested that other indices of vitamin D status, such as free 25-OHD, bioavailable 25-OHD and the ratio 24,25(OH)2D / 25OHD (vitamin D metabolite ratio; VMR), may provide additional information beyond the isolated measurement of 25(OH)D.

Besides the lack of clinical information there are analytical issues that limit a wider use of novel vitamin D indices. The determination of free and bioavailable 25-OHD requires the measurement of vitamin D binding protein (VDBP), a highly polymorphic protein. However, the analytical performance of commercial ELISAs for the measurement of VDBP varies substantially and depends on the capture antibody used. Only mass spectrometry is capable of capturing all forms correctly and can thus provide a true result. For 24,25(OH)2D very few commercial methods are available so far. Furthermore, no international standard materials are available to help laboratories aligning their results. A recent evaluation of a multiplex LC-MS/MS with immune-affinity chromatography showed poor performance, which underlines the need for sensitive and accurate LC-MS/MS methods for the determination of vitamin D metabolites and VDBP.

Therefore, well characterized methods for the measurement of vitamin D and their metabolites are needed. The use of these methods in different cohorts of healthy and diseased subjects and the vitamin D metabolite ratio as another interesting index will help to understand their practical value for the assessment of vitamin D status. The present projects aims to develop and validate sensitive and accurate methods for the simultaneous measurement 25-OHD, 24,25-dihydroxy vitamin D and 1,25-(OH)2D. These methods will be used to explore the vitamin D status in different cohorts of healthy and diseased subjects.

Dissertation (Christoph Walcher)

The number of modern pharmaceutical formulations containing special drug delivery systems for the controlled release of active substances is constantly increasing. The main objectives of these delivery systems are to achieve a prolonged therapeutic effect and predictable drug release kinetics over a defined time period. Classical delivery systems for the controlled release of pharmaceutical active substances are coated pills for oral administration, transdermal pads or drug/device combination products like drug-eluting stents. In recent years more and more parenterally administered formulations for controlled drug release were developed. Although the number of these dosage forms is permanently rising, there are currently no compendial dissolution test methods available, which are especially designed for testing these formulations. For in vitro testing of a dosage form performance under standardized conditions, dissolution is a very powerful method. On the one hand these tests are used during the development of formulations to predict the in vivo performance by establishing in vitro-in vivo correlations (IVIVCs), on the other hand they are also used for the quality control during the production of such systems. Although these tests are already routine, there are currently no formal FDA guidelines available for in vitro release testing of injectable controlled release systems to establish IVIVCs. Since extended release dosage forms usually release the active substance over a long period of time like weeks, months or even years to maintain a constant level, a real time dissolution test would be rather time consuming. Therefore, accelerated in vitro release methods are needed for quality control purposes and to establish IVIVCs during development much faster.

The aim of this work is the development of alternative strategies for the dissolution testing of parenteral administered controlled release dosage forms. Adjustment of known methods and development of new devices for sample placement is needed to overcome existing problems. To obtain reproducible standard methods it is also necessary to provide as simple routines as possible with the possibility of preferably total automatization. The development and evaluation of fast, reproducible and easy to use dissolution testing methods with good discriminatory abilities, which can be used as methods for IVIVCs and for quality control, are further objectives of this dissertation.