title: Study of the structures of photodegradation impurities and pathways of photodegradation of cilnidipine by liquid chromatography/Q-Orbitrap mass spectrometry.
abstract: The structures of photodegradation impurities in cilnidipine were studied by liquid chromatography/Q-Orbitrap mass spectrometry (LC/Q-Orbitrap MS) for the further improvement of the official monographs in Pharmacopoeias. The complete fragmentation patterns of impurities were investigated to obtain their structural information. Two pathways of photodegradation of cilnidipine were also explored to clarify the source of impurities in cilnidipine.
  
  
  
  Chromatographic separation was performed on a Boston Group C18 column (250 mm × 4.6 mm, 5 μm). The mobile phase consisted of acetonitrile/H2 O at a ratio of 75:25 (v/v). In order to determine the m/z values of the molecular ions and formulas of all detected impurities, full scan LC/MS in both positive and negative ion modes was firstly performed using a Thermo LC system coupled with a Q-Orbitrap high-resolution mass spectrometer. LC/MS/MS analysis was also carried out on target compounds to obtain as much structural information as possible.
  
  
  
  Five novel photodegradation impurities of cilnidipine were separated and identified based on the high-resolution MS/MS data. Impurity III was synthesized and its structure was confirmed by (1) H-NMR and (13) C-NMR data. Two photodegradation pathways to produce different photodegradation impurities were also revealed in this study.
  
  
  
  Among those impurities, impurities II and III were the main impurities which existed in the cilnidipine available on the market. Impurity II (the Z-isomer) was mainly produced when cilnidipine powder was directly exposed to daylight while impurity III (containing a piperidine ring) was mainly produced when cilnidipine was exposed to daylight in an ethanolic solution. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, China.|Zhejiang Institute for Food and Drug Control, Hangzhou, 310053, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zeng
authors.affiliation: School of Medicine, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Zhejiang Institute for Food and Drug Control, Hangzhou, 310053, China.
authors.forename: Bingqi
authors.initials: B
authors.lastname: Zhu
authors.affiliation: College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhong
authors.affiliation: College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Shan
authors.affiliation: Zhejiang Institute for Food and Drug Control, Hangzhou, 310053, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004095:Dihydropyridines / Q000737:chemistry*; D004340:Drug Contamination; D013058:Mass Spectrometry; D010782:Photolysis; D053719:Tandem Mass Spectrometry
chemical_list: D004095:Dihydropyridines; C065927:cilnidipine