title: Identification, characterization and quantification of a new impurity in deferasirox active pharmaceutical ingredient by LC-ESI-QT/MS/MS.
abstract: An unknown impurity was detected in deferasirox drug substance by a newly developed high performance liquid chromatography (HPLC) method. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry using electrospray ionization source and Q-trap mass analyzer (LC-ESI-QT/MS/MS). Based on LC-MS/MS data and knowledge of the synthetic scheme of deferasirox, this impurity was proposed as the regio-isomer of deferasirox. Structural confirmation of this impurity was unambiguously carried out by synthesis followed by characterization using nuclear magnetic resonance (NMR), infrared spectroscopy (IR), mass spectrometry, elemental analysis (EA) and the impurity was confirmed as 2-[3,5-bis(2-hydroxy-phenyl)-[1,2,4]-triazol-1-yl]-benzoic acid (Imp-1). The newly developed method was validated according to ICH guidelines. The resolution between Imp-1 and deferasirox was found to be more than 6.0 and the detection limit of impurities was in the range of 0.0005-0.01%, indicating high selectivity and sensitivity of the newly developed method.
authors.affiliation: Jubilant Life Sciences Ltd., Analytical Research Department, R&D Centre, C-26, Sector-59, Noida, Uttar Pradesh 201301, India. saji thomas@jubl.com
authors.forename: Saji
authors.initials: S
authors.lastname: Thomas
authors.forename: Subhash
authors.initials: S
authors.lastname: Chandra Joshi
authors.forename: Dharam
authors.initials: D
authors.lastname: Vir
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Agarwal
authors.forename: Raghavendra Desai
authors.initials: RD
authors.lastname: Rao
authors.forename: I
authors.initials: I
authors.lastname: Sridhar
authors.forename: Cijo M
authors.initials: CM
authors.lastname: Xavier
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Mathela
mesh_terms: D001565:Benzoates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000592:standards; D000077588:Deferasirox; D004340:Drug Contamination; D017408:Guidelines as Topic; D007502:Iron Chelating Agents / Q000737:chemistry*; D007536:Isomerism; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014230:Triazoles / Q000737:chemistry*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox