• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
ZHANG Keke, LIN Jinsheng, ZHENG Lewei, WANG Jichao, LI Min, SHEN Weiyang. Structural elucidation and mechanism study for Hofmann-Martius-like rearrangement products in duloxetine hydrochloride under the process condition[J]. Journal of China Pharmaceutical University, 2023, 54(4): 474-482. DOI: 10.11665/j.issn.1000-5048.2023022102
Citation: ZHANG Keke, LIN Jinsheng, ZHENG Lewei, WANG Jichao, LI Min, SHEN Weiyang. Structural elucidation and mechanism study for Hofmann-Martius-like rearrangement products in duloxetine hydrochloride under the process condition[J]. Journal of China Pharmaceutical University, 2023, 54(4): 474-482. DOI: 10.11665/j.issn.1000-5048.2023022102
shu

Structural elucidation and mechanism study for Hofmann-Martius-like rearrangement products in duloxetine hydrochloride under the process condition

  • 1.

    Center of Excellence For Modern Analytical Technologies, Zhejiang Huahai Pharmaceutical Co., Ltd., Linhai 317024

  • 2.

    School of Science, China Pharmaceutical University, Nanjing 211198, China

More Information
  • Received Date: February 20, 2023
  • Revised Date: August 19, 2023
    Graphical Abstract
    • Abstract
  • Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.
    • FullText(HTML)
    • References (7)
  • [1]
    Osawa RA, Carvalho AP, Monteiro OC, et al. Degradation of duloxetine: identification of transformation products by UHPLC-ESI ( +)-HRMS/MS, in silico toxicity and wastewater analysis[J]. J Environ Sci, 2019, 82: 113-123.
    [2]
    Baradwan S, Alshahrani MS, Alkhamis WH, et al. Preoperative duloxetine on postoperative pain after laparoscopic gynecological surgeries: a systematic review and meta-analysis of randomized controlled trials[J]. J Gynecol Obstet Hum Reprod, 2022, 51(3): 102305.
    [3]
    Tibor M, Gyula S, Eniko M, et al. Duloxetine salts:
    US20090209617[P]. 2009-08-20.
    [4]
    Lin JS, Chen FF, Bao CH, et al. Investigation of an artificial solution degradant of linagliptin: an undesired linagliptin urea derivative generates in sample preparation of linagliptin tablet treated by sonication in acetonitrile containing diluent[J]. J Pharm Biomed Anal, 2022, 210: 114540.
    [5]
    Lin JS, Huang TP, Feng MX, et al. Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation[J]. J Pharm Biomed Anal, 2019, 168: 181-188.
    [6]
    Arava VR, Bandat Makuru SU, Cherukuri KR, et al. Stability indicating nature of RP-HPLC method for determination of impurity profile and degradation impurities in duloxetine hydrochloride[J]. Der Pharma Chemica, 2012, 4(4): 1735-1741.
    [7]
    Arava VR, Siripalli UBR, Bandatmakuru SR. Novel acid catalysed rearrangement of duloxetine[J]. IJC-B, 2007, 46B (10): 1695-1698.
    • Related Articles

  • Related Articles

    [1]YIN Hao, WANG Wei, MIN Qianhao. Advances in mass-encoded probes for multiplex mass spectrometric detection[J]. Journal of China Pharmaceutical University, 2023, 54(6): 706-717. DOI: 10.11665/j.issn.1000-5048.2023062902
    [2]WANG Maolin, GUO Weiwei, ZHENG Yueqin. Advances in fluorescence probes for detection of hydrogen polysulfides[J]. Journal of China Pharmaceutical University, 2023, 54(5): 553-563. DOI: 10.11665/j.issn.1000-5048.2023042804
    [3]CHEN Yue, HAO Meixi, JU Caoyun, ZHANG Can. Design, synthesis and application of AIE fluorescent probe for lipid raft[J]. Journal of China Pharmaceutical University, 2020, 51(5): 514-521. DOI: 10.11665/j.issn.1000-5048.20200502
    [4]GE Yiran, YANG Jian, LI Yuyan, XU Yungen. Advances of near-infrared fluorescent probes for detection of Alzheimer′s disease[J]. Journal of China Pharmaceutical University, 2020, 51(2): 138-151. DOI: 10.11665/j.issn.1000-5048.20200203
    [5]GUO Anping, JIANG Fen, XU Xiaoli, YOU Qidong, LI Yuyan. Design, synthesis and biological application of affinity-based small molecular probe for Hsp90 endoplasmic reticulum paralogue of Grp94[J]. Journal of China Pharmaceutical University, 2019, 50(2): 161-167. DOI: 10.11665/j.issn.1000-5048.20190205
    [6]WANG Shuo, SUN Xiaoyan, CHEN Jinlong. Application of rhodamine-based fluorescent molecular probes in visualization of cellular pyruvic acid[J]. Journal of China Pharmaceutical University, 2018, 49(1): 79-86. DOI: 10.11665/j.issn.1000-5048.20180111
    [7]LI Li, XU Fengguo, CHEN Jinlong. Exploration of enzyme-MnO2 nanosheets hybridization probe for sensitively colorimetric self-indicating of glucose[J]. Journal of China Pharmaceutical University, 2017, 48(4): 453-460. DOI: 10.11665/j.issn.1000-5048.20170410
    [8]ZHOU Lin, LIU Wei, DI Bin, CHEN Jinlong. Synthesis and application of a fluorescent molecular probe for rapid detection of sulfur dioxide residues in traditional Chinese herbs[J]. Journal of China Pharmaceutical University, 2015, 46(4): 444-449. DOI: 10.11665/j.issn.1000-5048.20150410
    [9]ZHAO Zekai, WANG Lu, XUE Jingwei, ZHANG Can. Development of reduction response probes[J]. Journal of China Pharmaceutical University, 2014, 45(5): 535-539. DOI: 10.11665/j.issn.1000-5048.20140505
    [10]ZHAO Bo, CHEN Jiang-ning, ZHANG Jun-feng. Copper (II) fluorescent probe for detecting nitric oxide[J]. Journal of China Pharmaceutical University, 2011, 42(6): 490-494.

Catalog

    Get Citation
    PDF
    XML
    Article views (96) PDF downloads (246) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：303132

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return