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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Isolation and Characterization of An Allergic Dimer Impurity in Cefmenoxime Hydrochloride by NMR and HR-MS Method

Author(s): Jin Li, Shang-Chen Yao, Li-hui Yin, Chang-Qin Hu and Ming-Zhe Xu*

Volume 18, Issue 7, 2022

Published on: 29 April, 2022

Page: [710 - 718] Pages: 9

DOI: 10.2174/1573412918666220318103024

Price: $65

Abstract

Background: We systematically characterized an allergic dimer impurity in cefmenoxime hydrochloride raw material by UV, IR, HR-MS, 1D, and 2D NMR for the first time.

Methods: The dimer stock solution of cefmenoxime hydrochloride was obtained by the degradation method. The target dimer impurity in the stock solution was separated by preparative RP-HPLC and purified by the freeze-drying method. By comparing the dimer to cefmenoxime hydrochloride, the functional groups corresponding to the characteristic peaks of UV and IR spectra were identified, and the molecular formula and mass fragmentation pattern were determined using HR-MS.

Results: Then, based on the full assignment of 1 H and 13 C NMR signals， the dimerized position was confirmed and its absolute configuration was identified by 1D and 2D NMR.

Conclusion: This study provided a structural basis for the allergic study of dimer impurities in cephalosporin drugs.

Keywords: Antibiotics, cephalosporin, Cefmenoxime hydrochloride, dimer impurity, nuclear magnetic resonance (NMR), mass spectrometry (MS).

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[1]
Jin, S.H. Research progress on cephalosporin allergic reaction. World Notes Antibiot, 1984, 3, 191-197.
[2]
Jin, S.H. Allergic reaction of antibiotics-I. Allergic reaction of β-lactam antibiotics. J. Clin. Pharmacol., 1986, 2, 251-257.
[3]
Jin, S.H.; Hu, C.Q. Study on allergic reactions to beta-lactam antibiotics. Bull. Med. Rec., 2002, 31, 22-23.
[4]
Jin, S.H. A review on relationship between quality of β-lactam antibiotics and allergic reactions. Chin. J. Antibiot., 1988, 13, 65-71.
[5]
Hu, C.Q.; Jin, S.H. Research progress of macromolecular impurities in β-lactam antibiotics and their analytical techniques. World Notes Antibiot., 1996, 17, 336-343.
[6]
Wang, Y.Y.; Chen, Y.; Hong, L.Y. Review on progresses of isolation and test methods for high-molecular weight polymer impurities in β-lactam antibiotics. Chin Pharm Aff, 2015, 29, 608-612.
[7]
Hu, C.Q. Developments on analysis of polymers of β-lactam antibiotics. Zhongguo Xin Yao Zazhi, 2008, 17, 2098-2102.
[http://dx.doi.org/10.3321/J.issn:1003-3734.2008.24.006]
[8]
Li, J.; Zhang, P.P.; Chong, X.M. Analysis of polymer impurities in co-amoxicillin and potassium clavulanate preparations. Yaowu Fenxi Zazhi, 2017, 37, 1430-1440.
[9]
Yang, M.Q.; Jin, S.H.; Hu, C.Q. Analysis of polymer impurities in related substances of benzylpenicillin sodium by HPLC -column-switching. Yaowu Fenxi Zazhi, 2009, 29, 1615-1620.
[10]
Li, J.; Zhang, P.P.; Yao, S.C. Analysis of polymer impurities in piperacillin sodium andtazobactam sodium for inJection. Yaowu Fenxi Zazhi, 2019, 39, 1279-1294.
[http://dx.doi.org/10.16155/J.0254-1793.2019.07.16]
[11]
Li, J.; Yao, S.C.; Yin, L.H. Analysis of polymer impurities in ceftazidime raw materials andpreparations. Yao Xue Xue Bao, 2020, 55, 1889-1896.
[12]
Li, J.; Yao, S.C.; Yin, L.H. Analysis of polymer impurities in cefixime raw materialsand preparations. Yao Xue Xue Bao, 2020, 55, 2442-2448.
[http://dx.doi.org/10.16438/J.0513-4870.2020-0643]
[13]
Li, J.; Yao, S.C.; Yin, L.H. Analysis of polymer impurities in cefotaxime sodium raw materials. Chin. J. Antibiot., 2020, 45, 883-892.
[http://dx.doi.org/10.13461/J.cnki.c]
[14]
Xu, Y.; Wang, D.; Tang, L.; Wang, J. Separation and characterization of allergic polymerized impurities in cephalosporins by 2D-HPSEC×LC-IT-TOF MS. J. Pharm. Biomed. Anal., 2017, 145, 742-750.
[http://dx.doi.org/10.1016/j.jpba.2017.07.063 ] [PMID: 28806571]
[15]
Campoli-Richards, D.M.; Todd, P.A. Cefmenoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 1987, 34(2), 188-221.
[http://dx.doi.org/10.2165/00003495-198734020-00002 ] [PMID: 3304966]
[16]
State Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China, 2015 Ed.; China Medical Science Press: Beijing, 2015, pp. 255-258.
[17]
State Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China, 2015 Ed.; China Medical Science Press: Beijing, 2020, p. 1094.
[18]
The united statespharmacopeia convention, 42; The United States Pharmacopeia Convention Inc: Roehville MD, 2019, 821,
[19]
Li, J.; Yao, S.C.; Yin, L.H. Analysis of polymer impurities in cefmenoxime hydrochloride raw materials and preparations. Yaowu Fenxi Zazhi, 2021, 41, 169-179.
[http://dx.doi.org/10.16155/J.0254-1793.2021.01.21]
[20]
Yao, X.S.; Chen, Y.J. NMR Spectrometer with Superconducting Magnet; China Medical Pharmaceutical Science and Technology Publishing House: Beijing, 1991, pp. 151-154.
[21]
Zhao, T.Z. 1H Nuclear Magnetic Resonance; Peking University Press: Beijing, 1983, pp. 30-44.
[22]
Zhao, T.Z. 13C Nuclear Magnetic Resonance; Henan Science and Technology Press: Zhengzhou, 1993, pp. 21-26.
[23]
Li, J.; Yao, S.C.; Yin, L.H. NMR spectroscopic characteristics of Cephalosporin E-isomer Impurities. Chung Kuo Yao Hsueh Tsa Chih, 2021, 56, 51-55.
[http://dx.doi.org/10.11669/cpJ.2021.11.00]
[24]
Li, Q.L. Spectral data analysis and structural elucidation of cefmenoxime hydrochloride. J. Mordern Food Pharm., 2007, 17, 34-36.

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