title: LC-ESI-MS/MS evaluation of forced degradation behaviour of silodosin: In vitro anti cancer activity evaluation of silodosin and major degradation products.
abstract: Silodosin (SLD) a novel α1-adrenoceptor antagonist was subjected to forced degradation involving hydrolysis (acidic, alkaline and neutral), oxidative, photolysis and thermal stress, as per ICH specified conditions. The drug underwent significant degradation under hydrolytic (acidic, alkaline and neutral) and oxidative stress conditions whereas, it was found to be stable under other stress conditions. A rapid, precise, accurate and robust chromatographic method for the separation of the drug and its degradation products (DPs) was developed on a Fortis C18analytical column (150×4.6mm, 5μm) using 0.1% formic acid and acetonitrile as a mobile phase in gradient elution mode at a flow rate of 1.0mL/min. A total of 5 (DP 1 to DP 5) hitherto unknown DPs were identified by LC-ESI-TOF-MS/MS experiments and accurate mass measurements. The most probable mechanisms for the formation of DPs have been proposed based on a comparison of the fragmentation of the [M+H]+ions of silodosin and its DPs. The major DPs (DP 1 and DP 2) were isolated and evaluated for anticancer activity using PC3 (human prostate cancer) cell lines by MTT assay. The results revealed that silodosin, DP 1 and DP 2 have potential anticancer activity with IC50values (μM) 72.74 (±4.51), 25.21 (±2.36), and, 114.07 (±11.90) respectively.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Chiguru
authors.initials: C
authors.lastname: Vishnuvardhan
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Baikadi
authors.initials: B
authors.lastname: Saibaba
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Lingesh
authors.initials: L
authors.lastname: Allakonda
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Swain
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: S
authors.initials: S
authors.lastname: Gananadhamu
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India; National Center for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500607,Telangana, India. Electronic address: srini@iict.res.in.
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad (NIPER-H), Balanagar, Hyderabad, 500037, Telangana, India. Electronic address: satish.niperhyd@gov.in.
authors.forename: N
authors.initials: N
authors.lastname: Satheeshkumar
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007211:Indoles / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000970:Antineoplastic Agents; D007211:Indoles; C095285:silodosin
keywords: Anti cancer activity; Forced degradation; Isolation of DPs; LC–MS/MS; MTT assay