Novel Analytical Workflow for Comprehensive Non-targeted Phytochemical Metabolic Profiling: FH-HES

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 chromatography mass spectrometry LC-MS/MS data can be directly correlated with pharmacological test results on a molecular level. Thus the understanding and interpretation of pharmacological properties is supported by structural and chemical information

Development, validation, and application of a novel LC-MS/MS trace analysis method for the simultaneous quantification of seven iodinated X-ray contrast media and three artificial sweeteners in surface, ground, and drinking water

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 sensitivities, a 10-fold sample enrichment step using a Genevac EZ-2 plus centrifugal vacuum evaporator that provided excellent recoveries (90 ± 6%) was selected for sample preparation. Limits of quantification below 10ng/L were obtained for all compounds. Furthermore, sample preparation recoveries and matrix effects were investigated thoroughly for all matrix types. Considerable matrix effects were observed in surface water and could be compensated by the use of four stable isotope-labeled internal standards. Due to their persistence, fractions of diatrizoic acid, iopamidol, and acesulfame could pass the whole drinking water production process and were observed also in drinking water. To monitor the fate and occurrence of these compounds, the validated method was applied to samples from different stages of the drinking water production process of the Industrial Works of Basel (IWB). Diatrizoic acid was found as the most persistent compound which was eliminated by just 40% during the whole drinking water treatment process, followed by iopamidol (80% elimination) and acesulfame (85% elimination). All other compounds were completely restrained and/or degraded by the soil and thus were not detected in groundwater. Additionally, a direct injection method without sample preparation achieving 3-20ng/L limits of quantification was compared to the developed method

Metabolomic Abnormalities in Serum from Untreated and Treated Dogs with Hyper- and Hypoadrenocorticism

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 treatment (n = 28), as well as with untreated (n = 35) and treated hypoadrenocorticism (n = 23) were analyzed and compared to apparently healthy dogs (n = 40). A validated targeted proton nuclear magnetic resonance (H-1 NMR) platform was used to quantify 123 parameters. Principal component analysis separated the untreated endocrinopathies. The serum samples of dogs with untreated endocrinopathies showed various metabolic abnormalities with often contrasting results particularly in serum concentrations of fatty acids, and high- and low-density lipoproteins and their constituents, which were predominantly increased in hyperadrenocorticism and decreased in hypoadrenocorticism, while amino acid concentrations changed in various directions. Many observed serum metabolic abnormalities tended to normalize with medical treatment, but normalization was incomplete when compared to levels in apparently healthy dogs. Application of machine learning models based on the metabolomics data showed good classification, with misclassifications primarily observed in treated groups. Characterization of metabolic changes enhances our understanding of these endocrinopathies. Further assessment of the recognized incomplete reversal of metabolic alterations during medical treatment may improve disease management.Peer reviewe

Antimicrobial polyethylene through melt compounding with quaternary ammonium salts

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 in 50°C warm water for 30 days, several were still antimicrobially active. No correlation between the number of exposed N+ head groups after leaching and the antibacterial activity was observed. There is however a qualitative correlation of the antibacterial activity with the contact angles and surface concentrations of N+ before leaching/storing in warm water

Thin-layer Chromatography–Nuclear Magnetic Resonance Spectroscopy – A Versatile Tool for Pharmaceutical and Natural Products Analysis: FH – HES Universities of Applied Sciences

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 power of mass spectrometry (MS). The TLC-MS interface simplifies the workflow dramatically to gain structural information directly from TLC separations. This article describes the potential of TLC-nuclear magnetic resonance spectroscopy (NMR) utilizing the TLC-MS interface to straightforwardly characterize zones of interest by NMR spectroscopy with a focus on quantification of active pharmaceutical ingredients (API) in formulations and identification of active principles in plant extracts

Potential of measured relative shifts in collision cross section values for biotransformation studies.

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 (CCSmeas) between parent drugs and their metabolites. Hence, the purpose of the present article was (i) to investigate if such relative shifts in CCSmeas were biotransformation-specific and (ii) to highlight their potential benefits for biotransformation studies. First, mean CCSmeas values of 165 compounds were determined (up to n = 3) using a travelling wave IMS-MS device with nitrogen as drift gas (TWCCSN2, meas). Further comparison with their predicted values (TWCCSN2, pred, Waters CCSonDemand) resulted in a mean absolute error of 5.1%. Second, a reduced data set (n = 139) was utilized to create compound pairs (n = 86) covering eight common types of phase I and II biotransformations. Constant, discriminative, and almost non-overlapping relative shifts in mean TWCCSN2, meas were obtained for demethylation (- 6.5 ± 2.1 Å2), oxygenation (hydroxylation + 3.8 ± 1.4 Å2, N-oxidation + 3.4 ± 3.3 Å2), acetylation (+ 13.5 ± 1.9 Å2), sulfation (+ 17.9 ± 4.4 Å2), glucuronidation (N-linked: + 41.7 ± 7.5 Å2, O-linked: + 38.1 ± 8.9 Å2), and glutathione conjugation (+ 49.2 ± 13.2 Å2). Consequently, we propose to consider such relative shifts in TWCCSN2, meas (rather than absolute values) as well for metabolite assignment/confirmation complementing the conventional approach to associate changes in mass-to-charge (m/z) values between a parent drug and its metabolite(s). Moreover, the comparison of relative shifts in TWCCSN2, meas significantly simplifies the mapping of metabolites into metabolic pathways as demonstrated