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Separation and Identification of Related Substances in Candesartan Cilexetil Tablets by UHPLC-Q-TOF–MS

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Abstract

Related substances, such as process-related substances and degradation products, may affect the efficacy of drugs and cause adverse reactions. Therefore, identifying and controlling them is of the importance. A rapid ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF–MS) method has been developed for the separation and characterization of related substances in candesartan cilexetil tablets. After optimization, the method validation was followed according to ICH guidelines. The developed UHPLC method showed adequate specificity, sensitivity, accuracy, linearity, precision, stability and robustness for validation of analytical procedures. Commercial candesartan cilexetil tablets was subjected to stress testing (60 ℃, 90% RH and 4500 lx for ten days) and forced degradation studies (acidic, alkaline, oxidative and photolytic degradation conditions). A total of eleven related substances were detected and characterized. Among them, four related substances have not been reported in the literature yet, and one of them (RS7) was confirmed as candesartan cilexetil methoxy analog by reference substance. In addition, plausible mechanisms for the formation of these related substances are discussed. This study provides a useful reference for the quality control of candesartan cilexetil tablets.

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Data is available from the authors upon request.

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Funding

The project was supported by Zhejiang Province Public Welfare Technology Application Research Project > (NO. LGC21H300001).

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Author notes

  1. Lishi Yang and Xiao Gu author equally contributed to this work.

Authors and Affiliations

  1. Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region and College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China

    Lishi Yang & Xinyu Zhao

  2. Zhejiang Institute for Food and Drug Control, Hangzhou, 310004, Zhejiang, China

    Xiao Gu, Chenxiao Yan, Qiaofeng Tao, Liya Hong & Jinqi Zheng

  3. Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration, Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Provincial, Hangzhou, 310052, China

    Xiao Gu, Chenxiao Yan, Qiaofeng Tao, Liya Hong & Jinqi Zheng

Authors
  1. Lishi Yang
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  2. Xiao Gu
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  3. Chenxiao Yan
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  4. Qiaofeng Tao
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  7. Jinqi Zheng
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Contributions

Material preparation, data collection, analysis and original draft preparation: LY, XG and CY. Conceptualization, writing—review and editing: QT and XZ. Project administration: LH and JZ.

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Correspondence to Liya Hong or Jinqi Zheng.

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Yang, L., Gu, X., Yan, C. et al. Separation and Identification of Related Substances in Candesartan Cilexetil Tablets by UHPLC-Q-TOF–MS. Chromatographia 86, 247–254 (2023). https://doi.org/10.1007/s10337-023-04242-7

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  • DOI: https://doi.org/10.1007/s10337-023-04242-7

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