Selective androgen receptor modulators:in vitroandin vivometabolism and analysis
| العنوان: | Selective androgen receptor modulators:in vitroandin vivometabolism and analysis |
|---|---|
| المؤلفون: | Saskia S. Sterk, Mario Thevis, Eva de Rijke, Leendert A. van Ginkel, Martien L. Essers, Toine F H Bovee, Jeroen C.W. Rijk |
| المصدر: | Food Additives & Contaminants. Pt. A, Chemistry, Analysis, Control, Exposure & Risk Assessment, 30(9), 1517-1526 Food Additives & Contaminants. Pt. A, Chemistry, Analysis, Control, Exposure & Risk Assessment 30 (2013) 9 |
| بيانات النشر: | Informa UK Limited, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Novel Foods & Agrochains, Health, Toxicology and Mutagenesis, Drug Evaluation, Preclinical, Glucuronidation, Quinolones, Novel Foods & Agroketens, Aminophenols, Toxicology, High-performance liquid chromatography, BU Veterinary Drugs, Tosyl Compounds, Hydroxylation, sarms, chemistry.chemical_compound, Sulfation, Drug Stability, Limit of Detection, Acetamides, Anilides, BU Toxicology, Novel Foods & Agrochains, Directie, Nonsteroidal Anti-Androgens, media_common, Chemistry, BU Toxicology, urinary metabolites, Veterinary Drugs, General Medicine, BU Toxicologie, Novel Foods & Agroketens, Biochemistry, Lactates, Microsomes, Liver, Rikilt B&T Toxicologie en Effectanalyse, BU Toxicologie, doping control purposes, BU Dierbehandelingsmiddelen, Cell Line, Species Specificity, In vivo, Nitriles, Androgen Receptor Antagonists, Animals, Humans, media_common.cataloged_instance, European union, Demethylation, Chromatography, Public Health, Environmental and Occupational Health, Reproducibility of Results, Drugs, Investigational, General Chemistry, Amides, Metabolic Detoxication, Phase II, Selective androgen receptor modulator, mass-spectrometric characterization, Acetanilides, Cattle, Metabolic Detoxication, Phase I, Food Science |
| الوصف: | For future targeted screening in National Residue Control Programmes, the metabolism of seven SARMs, from the arylpropionamide and the quinolinone classes, was studied in vitro using S9 bovine liver enzymes. Metabolites were detected and identified with ultra-performance liquid chromatography (UPLC) coupled to time-of-flight mass spectrometry (ToF-MS) and triple quadrupole mass spectrometry (QqQ-MS). Several metabolites were identified and results were compared with literature data on metabolism using a human cell line. Monohydroxylation, nitro-reduction, dephenylation and demethylation were the main S9 in vitro metabolic routes established. Next, an in vivo study was performed by oral administration of the arylpropionamide ostarine to a male calf and urine samples were analysed with UPLC-QToF-MS. Apart from two metabolites resulting from hydroxylation and dephenylation that were also observed in the in vitro study, the bovine in vivo metabolites of ostarine resulted in glucuronidation, sulfation and carboxylation, combined with either a hydroxylation or a dephenylation step. As the intact mother compounds of all SARMs tested are the main compounds present after in vitro incubations, and ostarine is still clearly present in the urine after the in vivo metabolism study in veal calves, the intact mother molecules were selected as the indicator to reveal treatment. The analytical UPLC-QqQ-MS/MS procedure was validated for three commercially available arylpropionamides according to European Union criteria (Commission Decision 2002/657/EC), and resulted in decision limits ranging from 0.025 to 0.05 µg l–1 and a detection capability of 0.025 µg l–1 in all cases. Adequate precision and intra-laboratory reproducibility (relative standard deviation below 20%) were obtained for all SARMs and the linearity was 0.999 for all compounds. This newly developed method is sensitive and robust, and therefore useful for confirmation and quantification of SARMs in bovine urine samples for residue control programmes and research purposes. |
| وصف الملف: | application/octet-stream; application/pdf |
| تدمد: | 1944-0057 1944-0049 |
| DOI: | 10.1080/19440049.2013.810346 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1231437f9e51f5522d93188fc37934c https://doi.org/10.1080/19440049.2013.810346 |
| Rights: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....e1231437f9e51f5522d93188fc37934c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19440057 19440049 |
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| DOI: | 10.1080/19440049.2013.810346 |