title: Characterization of degradation products of silodosin under stress conditions by liquid chromatography/Fourier transform mass spectrometry.
abstract: BACKGROUND
  Silodosin (SDN) is a novel α1-adrenoceptor antagonist in the treatment of benign prostatic hyperplasia (BPH). The presence of degradation products in a drug affects not only the quality, but also the safety and efficacy of drug formulation. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate, identify and characterise of all possible degradation products of SDN which is mandatory in drug development processes.
  
  
  METHODS
  SDN was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC® BEH C18 (2.1 × 100 mm, 1.7 μm; Waters) column with mobile phase consisting of 0.1% formic acid (FA) in water (A) and 0.1% FA in acetonitrile (ACN) and methanol (MeOH) (1:1) (B) as organic modifier at a flow rate of 0.15 mL min-1in gradient elution mode. Identification and characterization of the degradation products was performed by mass spectrometry methods using an LTQ-Orbitrap mass spectrometer.
  
  
  RESULTS
  A total of five degradation products (DP1 to DP5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and high-resolution mass spectral data. A common degradation product (DP1) was observed under acidic and basic degradation conditions. DP2 was observed under acidic, DP4 and DP5 were observed under basic hydrolytic conditions, whereas DP3 was observed under oxidative conditions.
  
  
  CONCLUSIONS
  SDN was found to be labile under hydrolytic and oxidative conditions. The structures of all the degradation products were proposed. The most rational mechanisms for the formation of the degradation products under different stress conditions have been established. The proposed method can be effectively used to carry out the determination and detection of SDN and its degradation products. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India.|Division of Sophisticated Analytical Instrument Facility, CSIR - Central Drug Research Institute, Lucknow, 226 031, India.|Academy of Scientific and Innovative Research, New Delhi, 110001, India.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Pandeti
authors.affiliation: Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India.|Academy of Scientific and Innovative Research, New Delhi, 110001, India.
authors.forename: Tadigoppula
authors.initials: T
authors.lastname: Narender
authors.affiliation: National Centre for Mass Spectrometry, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500 007, India.|Academy of Scientific and Innovative Research, New Delhi, 110001, India.
authors.forename: Sripadi
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Division of Sophisticated Analytical Instrument Facility, CSIR - Central Drug Research Institute, Lucknow, 226 031, India.|National Centre for Mass Spectrometry, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500 007, India.|Academy of Scientific and Innovative Research, New Delhi, 110001, India.
authors.forename: Thota Jagadeswar
authors.identifier: http://orcid.org/0000-0003-2573-162X
authors.initials: TJ
authors.lastname: Reddy