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Goetz Schlotterbeck

Goetz Schlotterbeck
Institut für Rechtsmedizin

Prof. Dr.

About

75
Publications
12,626
Reads
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4,198
Citations
Additional affiliations
April 2006 - April 2010
Roche
Position
  • Project Leader
May 2010 - present
FHNW University of Applied Sciences and Arts
Position
  • Professor (Full)

Publications

Publications (75)
Article
Full-text available
Ion mobility spectrometry–mass spectrometry (IMS-MS) separates gas phase ions due to differences in drift time from which reproducible and analyte-specific collision cross section (CCS) values can be derived. Internally conducted in vitro and in vivo metabolism (biotransformation) studies indicated repetitive shifts in measured CCS values (CCS meas...
Article
Full-text available
The market for plant protection products (PPPs) is one of the most regulated. With increasing regulations for registering PPPs, its requirements take more effort and more testing. Meanwhile, there is also an increasing market for illegal PPPs. While legally registered PPPs are thoroughly tested and documented, illegal PPPs are sold upfront without...
Article
Full-text available
The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solut...
Article
Full-text available
The adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = 27), hyperadrenocorticism undergoing...
Article
Full-text available
Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated...
Article
Full-text available
In patients with obesity, accelerated nutrients absorption is observed. Xylitol and erythritol are of interest as alternative sweeteners, and it has been shown in rodent models that their acute ingestion reduces intestinal glucose absorption. This study aims to investigate whether a chronic intake of xylitol and erythritol impacts glucose absorptio...
Article
Full-text available
Background Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiell...
Article
We set up an automated screening process to routinely test 10 chiral supercritical fluid chromatography (SFC) methods - five columns combined with two co-solvents - as part of a chiral separation lab workflow. Proprietary software tools enabled automated method screening of racemates, parallel evaluation of the resulting chromatograms for enantiome...
Article
Full-text available
Numerous projects and industrial and academic collaborations benefit from state-of-the-art facilities and expertise in analytical chemistry available at the Swiss Universities of Applied Sciences. This review summarizes areas of expertise in analytical sciences at the University of Applied Sciences and Arts Northwestern Switzerland (FHNW), the Univ...
Article
Full-text available
A new and fully automated newborn screening method for mass spectrometry was introduced in this paper. Pathological relevant amino acids, acylcarnitines, and certain steroids are detected within 4 min per sample. Each sample is treated in an automated and standardized workflow, where a mixture of deuterated internal standards is sprayed onto the sa...
Article
In a screening of natural products for allosteric modulators of GABAA receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and t...
Article
Speciation of carbon during the anoxic corrosion of steel is poorly known, whereas its knowledge would be of great importance in connection with assessments of the safe disposal of ¹⁴C-containing irradiated steel in repositories for radioactive waste. The chemical form of the ¹⁴C-bearing organic compounds determines routes of migration from enginee...
Chapter
Metabolomics, also often referred as “metabolic profiling,” is the systematic profiling of metabolites in biofluids or tissues of organisms and their temporal changes. In the last decade, metabolomics has become more and more popular in drug development, molecular medicine, and other biotechnology fields, since it profiles directly the phenotype an...
Article
Full-text available
Selected mono- and bicationic quats were compounded with polyethylene. The physicochemical surface properties, leaching behavior, and antibacterial activity of such modified samples were investigated. Contact angle measurements and fluorescein binding assays showed the presence of quaternary ammonium groups at the surface. After storing the samples...
Article
Full-text available
The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis o...
Article
Full-text available
The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis o...
Article
Bile acids malabsorption (BAM) is encountered in numerous gastrointestinal pathologies and is a good example of a treatable cause of watery diarrhea after ileal resection. The gold standard for diagnosing BAM is the selenium homocholic acid taurine test (SeHCAT), an expensive and complex analysis. An alternative method is the quantification of 7α-h...
Article
Introduction: MGAT3 gene expression is implicated in oncogenic signaling pathways. We recently found that MGAT3 expression correlated with the presence of bisecting GlcNAc on N-glycoproteins in ovarian cancer cells. MGAT3 encodes the enzyme attaching bisecting GlcNAc to these glycoproteins. We investigated (i) how MGAT3 expression is regulated, (ii...
Article
A 24-year-old man known to consume illegal drugs was found dead in his apartment. A reclosable plastic zipper bag containing several hundred milligrams of a brown powder was found close to the dead body and the first assumption of the investigators was death due to heroin intoxication. Therefore, a legal autopsy was ordered. The following toxicolog...
Article
Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral...
Article
Full-text available
Bisecting GlcNAc on N-glycoproteins is described in E-cadherin-, EGF-, Wnt- and integrin- cancer-associated signaling pathways. However, the mechanisms regulating bisecting GlcNAc expression are not clear. Bisecting GlcNAc is attached to N-glycans through beta 1-4 N-acetylglucosaminyl transferase III (MGAT3), which is encoded by two exons flanked b...
Conference Paper
Full-text available
Introduction Minimal carry-over is an important quality criterion of modern auto sampler technology and a prerequisite for high throughput (HT) analysis. It is essential to minimize potential carry-over in an early stage of method development. Automated sample preparation systems, such as the PAL RTC offer many possibilities to minimize carry over...
Article
Full-text available
The understanding and interpretation of pharmacological properties on a molecular level is of great importance for many different fields of research. Our study provides a novel model work-flow for comprehensive metabolic profiling by structural identification of relevant metabolites not limited to phytochemistry applications. High resolution liquid...
Article
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Extracts prepared from the leaves of Phyllostachys edulis (bamboo) have received attention in pharmacological research due to their potent antitumor, anti-inflammatory, antimicrobial, and anti-ulcerogenic activities. In this study, anti-inflammatory effects of a bamboo leaf extract on tumor necrosis factor alpha-induced overproduction of interleuki...
Conference Paper
Introduction Automation is an ongoing trend in analytical chemistry including sample preparation, measurement and data processing. In the clinical setting high-throughput and fully automated analytical solutions are of special interest. Dried Blood Spot (DBS) analysis is an alternative method of sampling bio-fluids, where e.g. a blood sample is spo...
Article
Full-text available
A sensitive and ultra-fast method utilizing the laser diode thermal desorption ion source using atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for the quantitative analysis of BKM120, an investigational anticancer drug in human plasma. Samples originating from protein precipitation (PP)...
Article
A new method for the simultaneous determination of iodated X-ray contrast media (ICM) and artificial sweeteners (AS) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) operated in positive and negative ionization switching mode was developed. The method was validated for surface, ground, and drinking water samples. In order to gain higher...
Article
In Europe, bamboo is mainly known as ornamental plant, as a source for application in the wood and fiber industry and as an energy crop. However, a growing interest in alternative use of bamboo can be observed because this fast growing plant provides a rich natural source of promising phytochemicals and exhibits many beneficial physiological effect...
Article
Phyllostachys edulis Carriere (Poaceae) has received considerable attention in pharmacological research due to their potent antitumor, anti-inflammatory, antimicrobial, and antiulcerogenic activities. In this study, we investigated the antiinflammatory effects of two leaf extracts (young versus old harvested leaves) prepared from Phyllostachys edul...
Article
A systematic comparison between two labeling approaches for the investigation of the in vitro metabolic pattern of pharmaceutical drugs was performed by examining the use of (i) radiolabeled drugs analyzed with LC-MS-offline radiodetection and (ii) stable-isotope labeled drugs, used in a defined mixture with the unlabeled drug and analyzed by LC-MS...
Article
Full-text available
Background: Phospholipidosis (PLD) is a lysosomal storage disorder induced by a class of cationic amphiphilic drugs. However, drug-induced PLD is reversible. Evidence of PLD from animal studies with some compounds has led to discontinuation of development. Regulatory authorities are likely to request additional studies when PLD is linked to toxici...
Article
In the search for new natural compounds with acetylcholinesterase (AChE) inhibitory activity this study focused on galbanum, the oleo gum-resin from Ferula gummosa Boiss., which had shown AChE inhibitory activity in a screening. The isolation of bioactive compounds from plant extracts usually is laborious and time consuming. In an approach to accel...
Article
Isolation of bio-active compounds from plant extracts is laborious and time-consuming. A dichloromethane extract of galbanum, the oleo gum-resin from Ferula gummosa Boiss., had shown AChE inhibitory activity (1). For fast identification of active compounds, HPTLC bioautography was combined with HPTLC-MS/NMR. After pre-fractionation of the extract b...
Article
Full-text available
Thin-layer chromatography (TLC) is a mature and very established technique, frequently used in many fields of applications ranging from natural product analysis to chemical or pharmaceutical applications. The introduction of a commercially available TLC–MS interface was a major step complementing the ease of use of TLC with structural elucidation p...
Article
Dysfunctional N-methyl-d-aspartate (NMDA) receptor neurotransmission has been implicated in the pathophysiology of schizophrenia. It is thought that this abnormal functioning can be corrected by increasing availability of the NMDA co-agonist glycine through inhibition of glycine transporter type 1 (GlyT1). Herein is described the pharmacologic prof...
Article
Metabonomics, also often referred to as "metabolomics" or "metabolic profiling," is the systematic profiling of metabolites in bio-fluids or tissues of organisms and their temporal changes. In the last decade, metabonomics has become increasingly popular in drug development, molecular medicine, and other biotechnology fields, since it profiles dire...
Article
Liquid chromatography (LC)-solid-phase extraction (SPE)-nuclear magnetic resonance (NMR)-mass spectrometry (MS) coupling is a key technology for fast and thorough structure elucidation of valuable mass-limited samples. Laborious serial isolation and purification procedures of metabolites, byproducts or impurities from complex biomatrices, natural p...
Article
Detailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) has been us...
Article
Full-text available
In this work, the results of metabolic profiling of urine from a preclinical comparative profiling study with the two biphosphonates ibandronate and zoledronate are reported. Toxicological assessment showed very different effects for the two compounds. Ibandronate did not cause major signs of toxicity, whereas zoledronate elicited hepatotoxicity an...
Article
The state-of-the-art of nuclear magnetic resonance spectroscopy, mass spectrometry and statistical tools for the acquisition and evaluation of complex multidimensional spectroscopic data in metabolic profiling is reviewed in this article. The continuous evolution of the sensitivity, precision and throughput has made these technologies powerful and...
Article
Selecting drug candidates based on toxicity is an important step in early drug development. In this case study, it is shown how metabonomics is applied to a ranking study, in which drug candidates with equal pharmacological activities are selected based on least toxic side effects. The metabonomic analyses were carried out on an animal study that f...
Article
For the analysis of the spectra of complex biofluids, preprocessing methods play a crucial role in rendering the subsequent data analyses more robust and accurate. Normalization is a preprocessing method, which accounts for different dilutions of samples by scaling the spectra to the same virtual overall concentration. In the field of 1H NMR metabo...
Article
The assignment of significantly changed NMR signals, which were identified with the help of multivariate models, to individual metabolites in biofluids is a manual and tedious task requiring knowledge in chemometrics and NMR spectroscopy. Metabolite projection analysis, introduced in this work, allows automatic linking of multivariate models with m...
Article
The throughput of a previously described NMR-based -assay has been increased by a factor of at least 4 as a consequence of adapting the system to chemical shift imaging; by using a 19-capillary system the enantiomeric purity of 5600 samples can be measured per day.
Article
The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here together with a brief summary of published studies. To provide a comprehensive assessment of this approach, the Consortium for Metabonomic Toxicology (COMET) has been formed between six pharmaceutical companies and Imperial College of Science, Technolo...
Article
Metabonomic analysis of biofluids and tissues utilizing high-resolution NMR spectroscopy and chemometric techniques has proven valuable in characterizing the biochemical response to toxicity for many xenobiotics. To assess the analytical reproducibility of metabonomic protocols, sample preparation and NMR data acquisition were performed at two site...
Article
A new triple-resonance (TXI) (1H, 13C, 15N) high-resolution nuclear magnetic resonance (NMR) capillary probe with 2.5-microL NMR-active sample volume (V(obs)) was built and tested for applications with mass- and volume-limited samples and for coupling of microbore liquid chromatography to NMR. This is the first microliter probe with optimized coil...
Article
Um einen Faktor 10 lässt sich die Messzeit für die Aufnahme hochaufgelöster NMR-Spektren mit einem gewöhnlichen NMR-Spektrometer reduzieren. Die Zeitersparnis gelingt durch Chemical-Shift-Imaging an parallel angeordneten, zu Kapillarbündeln zusammengefassten Proben. Das Bild zeigt eine Querschnittsaufnahme eines Bündels aus neun 1-mm-Kapillaren, di...
Article
A reduction of a factor of 10 in the time needed to measure highly resolved NMR spectra of multiple samples can be achieved with any NMR spectrometer by using a combination of chemical shift imaging and a compartmented detection volume consisting of a bundle of capillaries. The picture shows the cross-sectional image of a bundle of nine 1-mm capill...
Article
The synthesis of several substrate analogues of the enzyme β,β-carotene 15,15′-monooxygenase is reported. The substrate specificity of enriched enzyme fractions isolated from chicken intestinal mucosa was investigated. Regarding substrate binding/cleavage, these experiments demonstrate that i) any deviation from the `rod-like' β,β-carotene structur...
Article
In this technical note we describe the setup and application of automated sample preparation and usage of flow-through NMR equipment for the characterization of ligand binding on proteins. In addition, we focus on the perspectives of automated analysis of 2D HSQC spectra to identify changes in patterns indicative for ligand binding or changes of sa...
Article
The hyphenation of chromatographic separation techniques with NMR spectroscopy is one of the most powerful and time-saving methods for the separation and structural elucidation of unknown compounds and molecular compositions of mixtures. Most of the routinely used NMR flow-cells have detection volumes between 40–180 μL for conventional separations...
Article
Summary The characterisation of fatty alcohol ethoxylate based surfactants by on-line LC-NMR coupling is described. Different surfactant mixtures were separated by a mixed exclusion-adsorption method of liquid chromatography and simultaneously characterised by 1H-NMR spectroscopy. Information about the degree of oligomerisation of the ethylene oxid...
Article
This paper presents the application of directly coupled capillary high-performance liquid chromatography (capillary HPLC) and proton high-field nuclear magnetic resonance spectroscopy (NMR) for structural elucidation of a so-far unknown kitol isomer. One- and two-dimensional continuous- and stopped-flow NMR spectra were recorded in a 180 μm i.d. ca...
Article
The comparison of two different types of RP stationary phases in their ability to separate cis/trans isomers of retinoic acid (tretinoin) has been investigated by LC-NMR coupling. Only by recording of 1H NMR spectra the structural identification of the separated compounds was possible, since their absorption coefficients are very similar and their...
Article
Zeitaufwendige Abspaltungs‐ und Isolierungsschritte werden durch die Methode der Suspensions‐ ¹ H‐Magic‐Angle‐Spinning(MAS)‐NMR‐Spektroskopie überflüssig, die eine Synthesekontrolle an einer einzelnen Harzpartikel im Nanoliterdetektionsbereich ermöglicht. Am Beispiel einer Hydantoin‐Reaktionssequenz wurde dieses für die kombinatorische Chemie effiz...
Article
Laborious cleavage and isolation steps are avoided! The method of 1H magic angle spinning (MAS) NMR spectroscopy can be used to monitor the course of the synthesis on a single resin particle in a suspended sample in the nanoliter detection range. This extremely useful technique for combinatorial chemistry was tested on a hydantoin reaction sequence...
Article
The direct on-line coupling between capillary high-performance liquid chromatography (capillary HPLC) and proton high-field nuclear magnetic resonance (NMR) spectrometry has been used to derive structural information about constituents of a mixture of vitamin A derivatives. 1H NMR spectra were recorded in the stopped-flow and continuous-flow mode w...
Article
Summary A supercritical carbon dioxide hop extract has been analysed using on-line coupling of high performance liquid chromatography (HPLC) with1H nuclear magnetic resonance (NMR) spectroscopy. For the first time high quality NMR spectra of the six major hop bitter acids were recorded by employing the stopped-flow detection mode. The resolution of...
Article
Coupling HPLC and NMR is one of the most powerful techniques for simultaneous separation and structural elucidation of unknown compounds in mixtures. To date, however, minimizing the detection volume, as is required when coupling NMR with miniaturized separation techniques, has been accompanied by a dramatic loss in resolution of the NMR spectra. H...
Article
Even though their HPLC peaks overlap, vitamin A acetate isomers 1 (11-cis) and 2 (11,13-di-cis) can be distinguished and their 1H NMR spectra measured. Coupled HPLC and 1H NMR spectroscopy is the method of choice.

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