title: Stability-indicating reversed-phase HPLC method development and characterization of impurities in vortioxetine utilizing LC-MS, IR and NMR.
abstract: The current study reports the development and validation of a stability-indicating reversed phase HPLC method for the separation and identification of potential impurities in vortioxetine, a recently developed antidepressant. The structures of a new compound and four process-related impurities formed during the synthesis were characterized and confirmed by NMR, MS, and IR spectroscopy analyses. The most probable formation mechanisms of the impurities identified were proposed. Based on the characterization data, the new compound was proposed to be 1-[4-[(2,4-dimethylphenyl)thio]phenyl]-piperazine. In addition, an efficient chromatographic method was optimized to separate and quantify the impurities, which were obtained in the 0.05-0.75 μg/mL range. The developed HPLC method was validated with respect to accuracy, precision, linearity, robustness, and limits of detection and quantitation.
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.
authors.forename: Na
authors.initials: N
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, PR China.
authors.forename: Xingling
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 210009, PR China.
authors.forename: Kaihe
authors.initials: K
authors.lastname: Xiong
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. Electronic address: qiaogenzou@hotmail.com.
authors.forename: Qiaogen
authors.initials: Q
authors.lastname: Zou
authors.affiliation: College of Food Science and Light Industry, Nanjing Tech University, Nanjing 210009, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yao
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared / Q000379:methods; D013440:Sulfides / Q000032:analysis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000078784:Vortioxetine
chemical_list: D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine
keywords: Process-related impurities; Quantification; Structural elucidation; Vortioxetine