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Identification and quantification of five impurities in cloperastine hydrochloride.

Authors
  • Liu, He-Ying1
  • Cheng, Qi-Zhen2
  • Fu, Hui-Zheng1
  • Zhong, Zhen-Hua1
  • Xia, Hong-Ying1
  • Guo, Yan-Fang1
  • Zheng, Shuang-Shuang1
  • Yu, Shi-Shi1
  • 1 Jiangxi Institute for Drug Control, NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Province Engineering Research Center of Drug and Medical Device Quality, Nanchang, 330029, China. , (China)
  • 2 Jiangxi Institute for Drug Control, NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Province Engineering Research Center of Drug and Medical Device Quality, Nanchang, 330029, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Journal of pharmaceutical and biomedical analysis
Publication Date
Nov 02, 2020
Volume
193
Pages
113731–113731
Identifiers
DOI: 10.1016/j.jpba.2020.113731
PMID: 33197833
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cloperastine hydrochloride, a piperidine derivative, is a drug substance with a central antitussive effect and widely used in cough treatment; and its impurities have not been reported. Herein we isolated and identified five impurities (named as impurity A, B, C, D and E) in cloperastine hydrochloride bulk drug and developed a quantitative HPLC method. First, impurity A, B, C were enriched by ODS column chromatography and isolated by semi-preparative HPLC, at the same time, impurity D was purified by ODS column chromatography. Then, impurity E was enriched by strong acid degradation and purified by semi-preparative HPLC. At last, their structures were characterized by a variety of spectral data (MS, 1H NMR, 13C NMR, HSQC, HMBC and 1H-1H COSY). Impurity A was confirmed as 1-[2-(diphenylmethoxy)ethyl]piperidine, which having one less chloro-substituent compared with cloperastine. Impurity B was confirmed as 1-[2-[(2-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 2-chloro-substituent. Impurity C was confirmed as 1-[2-[(3-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 3-chloro-substituent. Impurity D was confirmed as (4-chlorophenyl)(phenyl)methanone, which was the raw material for the synthesis of cloperastine. Impurity E was confirmed as (4-chlorophenyl)(phenyl)methanol, which was an intermediate in the synthesis of cloperastine, and it was also a hydrolysate of cloperastine. Finally, the developed method was validated in terms of specificity, linearity, sensitivity, precision and accuracy. Copyright © 2020. Published by Elsevier B.V.

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