title: Identification, characterization and HPLC quantification of process-related impurities in Trelagliptin succinate bulk drug: Six identified as new compounds.
abstract: A sensitive, selective and stability indicating reversed-phase LC method was developed for the determination of process related impurities of Trelagliptin succinate in bulk drug. Six impurities were identified by LC-MS. Further, their structures were characterized and confirmed utilizing LC-MS/MS, IR and NMR spectral data. The most probable mechanisms for the formation of these impurities were also discussed. To the best of our knowledge, six structures among these impurities are new compounds and have not been reported previously. The superior separation was achieved on an InertSustain C18 (250mm×4.6mm, 5μm) column in a gradient mixture of acetonitrile and 20mmol potassium dihydrogen phosphate with 0.25% triethylamine (pH adjusted to 3.5 with phosphate acid). The method was validated as per regulatory guidelines to demonstrate system suitability, specificity, sensitivity, linearity, robustness, and stability.
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zou
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Hui
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China. Electronic address: qiaogenzou@hotmail.com.
authors.forename: Qiaogen
authors.initials: Q
authors.lastname: Zou
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech. University, Nanjing 210009, PR China.
authors.forename: Pingkai
authors.initials: P
authors.lastname: Ouyang
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D012680:Sensitivity and Specificity; D013055:Spectrophotometry, Infrared / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D014498:Uracil; C000595449:trelagliptin
keywords: LC–MS; NMR; Process related impurity; Quantification; Structural elucidation; Trelagliptin succinate