title: LC-MS/MS structural characterization of stress degradation products including the development of a stability indicating assay of Darunavir: An anti-HIV drug.
abstract: Darunavir, an anti-HIV drug was subjected to forced degradation under acid, base, thermal and neutral hydrolysis, oxidation and photolysis as prescribed by ICH guidelines. Four major degradation products were formed under acid and base hydrolysis, while stable under neutral and thermal hydrolysis, oxidative and photolysis. The drug and its degradation products were separated on Hiber, LiChrospher® 60, RP-select B, C8 column (250mm×4.6mm i.d., 5μm) using 10mM ammonium acetate: acetonitrile (52:48, v/v) as mobile phase in an isocratic elution mode by LC. The degradation products were characterized by LC-MS/MS and fragmentation pathways were proposed. The proposed structures of degradation products were confirmed by HRMS and the LC method was validated with respect to specificity, linearity, accuracy, recovery, LOD and LOQ.
authors.affiliation: Analytical Chemistry Division, D215, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. Electronic address: rnrao55@yahoo.com.
authors.forename: R Nageswara
authors.initials: RN
authors.lastname: Rao
authors.affiliation: Analytical Chemistry Division, D215, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India.
authors.forename: B
authors.initials: B
authors.lastname: Ramachandra
authors.affiliation: Analytical Chemistry Division, D215, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India.
authors.forename: B
authors.initials: B
authors.lastname: Sravan
authors.affiliation: Analytical Chemistry Division, D215, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India.
authors.forename: Sara
authors.initials: S
authors.lastname: Khalid
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D001681:Biological Assay / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D000069454:Darunavir; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D010084:Oxidation-Reduction; D010782:Photolysis; D013449:Sulfonamides / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D000069454:Darunavir
keywords: AIDS; Anti-retroviral; Darunavir; Forced degradation; LC–MS/MS