Thyroid Hormone Metabolites Quantified in Pup and Adult Rat Cerebellum, Cortex and Whole-Brain Samples Using an Automated Online SPE-LC-MS/MS Method.

Changes in thyroid hormone (TH) levels in rat brain at early developmental stages are correlated with adverse effects on offspring development. To characterize the ability of substances to interfere with the TH concentrations in, e.g.

A Novel and Fast Online-SPE-LC-MS/MS Method to Quantify Thyroid Hormone Metabolites in Rat Plasma.

Since the focus in regulatory toxicology has drifted toward the identification of endocrine disruptors, the improvement in determination of alterations in the thyroid hormone system has become more important. THs are involved in several molecular processes important for a proper pre- and postnatal development so that disturbances can inter alia lead to incorrect brain maturation and/or disturbed metabolic processes (thermogenesis or lipolysis). In this publication, a new automated online solid-phase extraction (SPE)-liquid chromatography (LC)-tandem mass spectrometry (MS/MS, xLC-MS/MS) is introduced which simultaneously analyzes total T4, T3, rT3, T2, and T1.

Investigating the gut microbiome and metabolome following treatment with artificial sweeteners acesulfame potassium and saccharin in young adult Wistar rats.

To elucidate if artificial sweeteners modify fecal bacterial composition and the fecal and plasma metabolomes, Wistar rats from both sexes were treated for 28 days with acesulfame potassium (40 and 120 mg/kg body weight) and saccharin (20 and 100 mg/kg body weight). Targeted MS-based metabolome profiling (plasma and feces) and fecal 16S gene sequencing were conducted. Both sweeteners exhibited only minor effects on the fecal metabolome and microbiota.

Use of in vitro metabolomics in NRK cells to help predicting nephrotoxicity and differentiating the MoA of nephrotoxicants.

We describe a strategy using an in vitro metabolomics assay with tubular rat NRK-52E cells to investigate the Modes of Action (MoAs) of nephrotoxic compounds. Chemicals were selected according to their MoAs based on literature information: acetaminophen, 4-aminophenol and S-(trichlorovinyl-)L-cysteine (TCVC), (covalent protein binding); gentamycin, vancomycin, polymycin B and CdCl (lysosomal overload) and tenofovir and cidofovir (mitochondrial DNA-interaction). After treatment and harvesting of the cells, intracellular endogenous metabolites were quantified relative to vehicle control.

Antibiotic-Induced Changes in Microbiome-Related Metabolites and Bile Acids in Rat Plasma.

Various environmental factors can alter the gut microbiome's composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e.

Use cases, best practice and reporting standards for metabolomics in regulatory toxicology.

Metabolomics is a widely used technology in academic research, yet its application to regulatory science has been limited. The most commonly cited barrier to its translation is lack of performance and reporting standards. The MEtabolomics standaRds Initiative in Toxicology (MERIT) project brings together international experts from multiple sectors to address this need.

Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.

Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions.

New Advances in the Biosynthesis of Glycopeptide Antibiotics of the Vancomycin Type from Amycolatopsis mediterranei.

Linear biosynthesis products from balhimycin, a tricyclic glycopeptide antibiotic of the vancomycin type, were isolated from mutants of Amycolatopsis mediterranei. The structures of these intermediates, determined by NMR spectroscopy, give new impulses for the understanding of the vancomycin biosynthesis.

ESI Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI-FT-ICR-MS): A Rapid High-Resolution Analytical Method for Combinatorial Compound Libraries.

The direct determination of the elemental compositions of the components of compound collections from combinatorial chemistry is achieved by ESI-FT-ICR mass spectrometry. Coupling with HPLC opens up a new dimension in high-resolution, informative analysis. The improved resolution of ESI-FT-ICR mass spectrometry in comparison to quadrupole mass spectrometry in the measurement of a compound obtained by solid-phase synthesis is illustrated.

FT-IR Mapping-A New Tool for Spatially Resolved Characterization of Polymer-Bound Combinatorial Compound Libraries with IR Microscopy.

In the search for selective receptors, a promising approach is provided by immobilization of cyclopeptides on sensor surfaces (see picture) and subsequent detection of low molecular weight analytes with reflectometric interference spectroscopy (RIfS). Together with combinatorial chemistry, this innovative method offers a great potential for applications as sensors.