Study of the structures of photodegradation impurities and pathways of photodegradation of cilnidipine by liquid chromatography/Q‐Orbitrap mass spectrometry. (4th July 2016)

• Record Type: Journal Article
• Authors: Zeng, Hongxia; Wang, Fan; Zhu, Bingqi; Zhong, Weihui; Shan, Weiguang; Wang, Jian
• Is Part Of: Rapid communications in mass spectrometry. Volume 30:Number 15(2016)
• Page Start: 1771
• Page End: 1778
• Publication Date: 2016-07-04
• Subjects: Mass spectrometry -- Periodicals; 543.65
• DOI: 10.1002/rcm.7657
• Languages: English
• ISSNs: 0951-4198

Abstract

Abstract : Rationale: 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. Methods: 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. Results: 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. Conclusions: 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.