Selective androgen receptor modulators:in vitroandin vivometabolism and analysis
| Autor: | Saskia S. Sterk, Mario Thevis, Eva de Rijke, Leendert A. van Ginkel, Martien L. Essers, Toine F H Bovee, Jeroen C.W. Rijk |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
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 |
| Zdroj: | 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 |
| ISSN: | 1944-0057 1944-0049 |
| DOI: | 10.1080/19440049.2013.810346 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |