title: Identification, synthesis and quantification of process-related impurities in auraptene.
abstract: Impurities in chemically synthesized auraptene, an active pharmaceutical ingredient (API), were detected by a gradient reverse-phase high-performance liquid chromatography (RP-HPLC) method. Molecular weights and major product ions of these chemical compounds were determined by liquid chromatography/Triple Quadrupole (LC-MS/MS) analysis. Structural assignments were presumed as umbelliferone (Imp-I), (E)-6,7-dihydroxy-3,7-dimethyl-2-octene-umbelliferone (Imp-II), (E)-6,7-epoxy-3,7-dimethyl-2-octene-umbelliferone (Imp-III) and 4-methylauraptene (Imp-IV). The impurities were authentically synthesized, confirmed by nuclear magnetic resonance spectroscopy (NMR) and infrared spectroscopy (IR), and subsequently used as reference samples in routing HPLC system suitability testing for method specificity and detectability. Method specificity was further verified by forced degradation studies. The developed method was validated for characterization of impurities in synthesized auraptene according to the guidelines of the International Conference on Harmonization (ICH) in our laboratory.
authors.affiliation: The Key Laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi College of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China 330004.
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Li
authors.forename: Hai-Fang
authors.initials: HF
authors.lastname: Chen
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Tu
authors.forename: Pu-Zhao
authors.initials: PZ
authors.lastname: Zhang
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Wang
authors.forename: Jin-Bin
authors.initials: JB
authors.lastname: Yuan
authors.forename: Wu-Liang
authors.initials: WL
authors.lastname: Yang
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003374:Coumarins / Q000032:analysis / Q000138:chemical synthesis* / Q000592:standards; D004339:Drug Compounding; D004340:Drug Contamination; D017408:Guidelines as Topic; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011786:Quality Control; D015203:Reproducibility of Results; D013055:Spectrophotometry, Infrared; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards
chemical_list: D003374:Coumarins; C105832:aurapten