title: Highly efficient, selective, sensitive and stability indicating RP-HPLC-UV method for the quantitative determination of potential impurities and characterization of four novel impurities in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI-IT/MS/MS.
abstract: A novel, sensitive, selective and stability indicating LC-UV method was developed for the determination of potential impurities of eslicarbazepine acetate. High performance liquid chromatographic investigation of eslicarbazepine acetate laboratory sample revealed the presence of several impurities. Three impurities were characterized rapidly and four impurities were found to be unknown. The unknown impurities were identified by liquid chromatography coupled with electrospray ionization, ion trap mass spectrometry (LC/ESI-IT/MS/MS). Structural confirmation of these impurities was unambiguously carried out by synthesis followed by characterization using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (FT-IR) and mass spectrometry (MS). Based on the spectroscopic, spectrometric and elemental analysis data unknown impurities were characterized as 5-acetyl-5,11-dihydro-10H-dibenzo [b,f]azepin-10-one, N-acetyl-5H-dibenzo[b,f]azepine-5-carboxamide, 5-acetyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate and 5-acetyl-5H-dibenzo[b,f]azepin-10-yl acetate. The newly developed LC-UV method was validated according to ICH guidelines considering eleven potential impurities and four new impurities to demonstrate specificity, precision, linearity, accuracy and stability indicating nature of the method. The newly developed method was found to be highly efficient, selective, sensitive and stability indicating. A plausible pathway for the formation of four new impurities is proposed.
authors.affiliation: Jubilant Life Sciences Ltd., Analytical Research Department, R&D Centre, C-26, Sector - 59, Noida, Uttar Pradesh 201 301, India. saji thomas@jubl.com
authors.forename: Saji
authors.initials: S
authors.lastname: Thomas
authors.forename: Amber
authors.initials: A
authors.lastname: Bharti
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Maddhesia
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Shandilya
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Agarwal
authors.lastname: Dharamvir
authors.forename: Sujay
authors.initials: S
authors.lastname: Biswas
authors.forename: Vikas
authors.initials: V
authors.lastname: Bhansal
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Gupta
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Tewari
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Mathela
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D003984:Dibenzazepines / Q000737:chemistry*; D004340:Drug Contamination; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D013058:Mass Spectrometry / Q000379:methods / Q000592:standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D013056:Spectrophotometry, Ultraviolet / Q000379:methods / Q000592:standards; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D003984:Dibenzazepines; C416835:eslicarbazepine acetate