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In vivo metabolic investigation of silodosin using UHPLC-QTOF-MS/MS and in silico toxicological screening of its metabolites.
- Source :
-
Journal of mass spectrometry : JMS [J Mass Spectrom] 2016 Oct; Vol. 51 (10), pp. 867-882. - Publication Year :
- 2016
-
Abstract
- Silodosin (SLD) is a novel α1-adrenoceptor antagonist which has shown promising clinical efficacy and safety in patients with benign prostatic hyperplasia (BPH). However, lack of information about metabolism of SLD prompted us to investigate metabolic fate of SLD in rats. To identify in vivo metabolites of SLD, urine, feces and plasma were collected from Sprague-Dawley rats after its oral administration. The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis. A total of 13 phase I and six phase II metabolites of SLD have been identified in rat urine which includes hydroxylated, N-dealkylated, dehydrogenated, oxidative, glucosylated, glucuronide and N-sulphated metabolites, which are also observed in feces. In plasma, only dehydrogenated, N-dealkylated and unchanged SLD are observed. The structure elucidation of metabolites was done by fragmentation in MS/MS in combination with HRMS data. The potential toxicity profile of SLD and its metabolites were predicted using TOPKAT software and most of the metabolites were proposed to show a certain degree of skin sensitization and occular irritancy. Copyright © 2016 John Wiley & Sons, Ltd.<br /> (Copyright © 2016 John Wiley & Sons, Ltd.)
- Subjects :
- Administration, Oral
Animals
Chromatography, High Pressure Liquid
Computer Simulation
Humans
Inactivation, Metabolic
Male
Metabolomics
Prostatic Hyperplasia drug therapy
Rats, Sprague-Dawley
Solid Phase Extraction
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Adrenergic alpha-1 Receptor Antagonists metabolism
Adrenergic alpha-1 Receptor Antagonists toxicity
Indoles metabolism
Indoles toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9888
- Volume :
- 51
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of mass spectrometry : JMS
- Publication Type :
- Academic Journal
- Accession number :
- 27747994
- Full Text :
- https://doi.org/10.1002/jms.3795