In vivometabolic investigation of silodosin using UHPLC-QTOF-MS/MS andin silicotoxicological screening of its metabolites

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.

Computational Design and Application of Molecularly Imprinted/MWCNT Based Electrochemical Sensor for the Determination of Silodosin

“…Several methods have been reported for the determination of SDL such as, liquid chromatography with mass spectrometric detection (LC-MS/MS) [2][3][4], liquid chromatography/ Fourier transform mass spectrometry [5], LC-ESI-MS/MS [6], (UPLC/MS/MS) [7,8], UHPLC-QTOF-MS/MS for in silico toxicological screening of its metabolites [9], (RP HPLC) [10][11][12][13][14], micellar electro kinetic chromatography [15], UV-VIS [16,17], charge transfer complex and validated stability-indicating spectrophotometric method [18,19] and spectrofluorimetry [20]. An electrochemical sensor based on Graphene Nanosheets/Gold nanoparticles/Nafion nanocomposite modified glassy carbon electrode was also reported [21].…”

Characterization of degradation products of silodosin under stress conditions by liquid chromatography/Fourier transform mass spectrometry

“…A few analytical and bioanalytical methods have been reported in the literature for the determination of SDN. It includes estimation of SDN alone or SDN and its in vivo metabolites in biological matrices …”