Profiling and in vivo Quantification of Proteins by High Resolution Mass Spectrometry: The Example of Goserelin, an Analogue of Luteinizing Hormone-Releasing Hormone

Author(s):  
Sophie Michalet ◽  
Philippe Favreau ◽  
Reto Stöcklin
Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 372 ◽  
Author(s):  
Priyanka Reddy ◽  
Aaron Elkins ◽  
Joanne Hemsworth ◽  
Kathryn Guthridge ◽  
Simone Vassiliadis ◽  
...  

Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals.


2020 ◽  
Vol 190 ◽  
pp. 113519
Author(s):  
Martin Uher ◽  
Martin Mžik ◽  
Jana Žďárová Karasová ◽  
David Herman ◽  
Lenka Čechová ◽  
...  

2016 ◽  
Vol 9 (5) ◽  
pp. 680-698 ◽  
Author(s):  
Ariane Wohlfarth ◽  
Markus Roman ◽  
Mikael Andersson ◽  
Fredrik C. Kugelberg ◽  
Xingxing Diao ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Frederike Nordmeier ◽  
Lilian H. J. Richter ◽  
Peter H. Schmidt ◽  
Nadine Schaefer ◽  
Markus R. Meyer

Abstract New Synthetic Opioids (NSOs) are one class of New Psychoactive Substances (NPS) enjoying increasing popularity in Europe. Data on their toxicological or metabolic properties have not yet been published for most of them. In this context, the metabolic fate of three NSOs, namely, trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzenacetamide (U-51754), trans-4-bromo-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzamide (U-47931E), and 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] acetamide (methoxyacetylfentanyl), was elucidated by liquid chromatography high-resolution mass spectrometry after pooled human S9 fraction (phS9) incubations and in rat urine after oral administration. The following major reactions were observed: demethylation of the amine moiety for U-51754 and U-47931E, N-hydroxylation of the hexyl ring, and combinations thereof. N-dealkylation, O-demethylation, and hydroxylation at the alkyl part for methoxyacetylfentanyl. Except for U-47931E, parent compounds could only be found in trace amounts in rat urine. Therefore, urinary markers should preferably be metabolites, namely, the N-demethyl-hydroxy and the hydroxy metabolite for U-51754, the N-demethylated metabolite for U-47931E, and the N-dealkylated metabolite as well as the O-demethylated one for methoxyacetylfentanyl. In general, metabolite formation was comparable in vitro and in vivo, but fewer metabolites, particularly those after multiple reaction steps and phase II conjugates, were found in phS9. These results were consistent with those of comparable compounds obtained from human liver microsomes, human hepatocytes, and/or human case studies.


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