title: Stability-indicating HPLC method development and structural elucidation of novel degradation products in posaconazole injection by LC-TOF/MS, LC-MS/MS and NMR.
abstract: Stress testing was carried out under acidic, alkaline, oxidative, thermal and photolytic conditions to evaluate the intrinsic stability of posaconazole injection. A total of four degradation products were detected and the drug was found to be susceptible to oxidative and thermal degradations. Three unknown degradants formed under oxidative stress condition were isolated by preparative HPLC and unambiguously elucidated by LC-TOF/MS, LC-MS/MS, (1)H NMR, (13)C NMR and 2D NMR techniques. Based on the spectrometric and spectroscopic information, these novel degradation products were unequivocally assigned as the N-oxides of posaconazole. Probable mechanisms for the formation of the degradants were proposed. A new and selective HPLC method was developed and validated to separate, detect and quantify all the degradants in posaconazole injection.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Simcere Pharmaceutical Co., Ltd., 699-18 Xuanwu Avenue, Nanjing 210042, PR China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jiangsu Simcere Pharmaceutical Co., Ltd., 699-18 Xuanwu Avenue, Nanjing 210042, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Jiangsu Simcere Pharmaceutical Co., Ltd., 699-18 Xuanwu Avenue, Nanjing 210042, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Jiangsu Simcere Pharmaceutical Co., Ltd., 699-18 Xuanwu Avenue, Nanjing 210042, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Jiangsu Simcere Pharmaceutical Co., Ltd., 699-18 Xuanwu Avenue, Nanjing 210042, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: dinglidl@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D010084:Oxidation-Reduction; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D014230:Triazoles; C101425:posaconazole
keywords: Degradation product; LC–MS/MS; N-oxide; NMR; Posaconazole; Structural elucidation