Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods
Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N -(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further ve...
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Published in | Scientific reports Vol. 12; no. 1; pp. 11665 - 6 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Nature Publishing Group UK
08.07.2022
Nature Publishing Group Nature Portfolio |
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Abstract | Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of
N
-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (
1
H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained. |
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AbstractList | Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of
N
-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (
1
H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained. Abstract Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained. Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained.Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained. Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained. |
ArticleNumber | 11665 |
Author | Ma, Ang Yuan, Wei-Feng Li, Xue Wang, Ming-Juan Xu, Hong-Xia Zhu, Lan-Xin Zhao, Sui-Hong Adams, Erwin Shen, Zong-Yong Chen, Mei-Ling Liu, Yu-Jing Hoogmartens, Jos |
Author_xml | – sequence: 1 givenname: Mei-Ling surname: Chen fullname: Chen, Mei-Ling organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 2 givenname: Hong-Xia surname: Xu fullname: Xu, Hong-Xia organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 3 givenname: Wei-Feng surname: Yuan fullname: Yuan, Wei-Feng organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 4 givenname: Sui-Hong surname: Zhao fullname: Zhao, Sui-Hong organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 5 givenname: Xue surname: Li fullname: Li, Xue organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 6 givenname: Lan-Xin surname: Zhu fullname: Zhu, Lan-Xin organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 7 givenname: Zong-Yong surname: Shen fullname: Shen, Zong-Yong organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 8 givenname: Yu-Jing surname: Liu fullname: Liu, Yu-Jing organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 9 givenname: Ming-Juan surname: Wang fullname: Wang, Ming-Juan email: wangmingjuan@sun-novo.com organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 10 givenname: Ang surname: Ma fullname: Ma, Ang organization: Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan – sequence: 11 givenname: Jos surname: Hoogmartens fullname: Hoogmartens, Jos organization: Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, KU Leuven – sequence: 12 givenname: Erwin surname: Adams fullname: Adams, Erwin email: erwin.adams@kuleuven.be organization: Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, KU Leuven |
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Cites_doi | 10.1039/C9RA10871H 10.1111/1541-4337.12938 10.1039/C7RA06341E 10.1002/jps.2600800305 10.1002/hlca.19870700121 10.3390/ijms23042187 10.1039/p19870001817 10.1371/journal.pone.0214598 10.1111/j.1751-1097.1988.tb08834.x 10.2147/DDDT.S239458 10.1039/C9RA09115G |
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Snippet | Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of
N... Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of... Abstract Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of... |
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SubjectTerms | 639/638 639/638/11/296 692/308 692/499 Chromatography Humanities and Social Sciences Impurities Irradiation Liquid chromatography Mass spectrometry Mass spectroscopy Metronidazole multidisciplinary NMR Nuclear magnetic resonance Pharmaceuticals Photodegradation Science Science (multidisciplinary) Scientific imaging Software Ultraviolet radiation Vagina |
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Title | Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods |
URI | https://link.springer.com/article/10.1038/s41598-022-15625-5 https://www.proquest.com/docview/2686431431 https://www.proquest.com/docview/2687725813 https://pubmed.ncbi.nlm.nih.gov/PMC9270378 https://doaj.org/article/658e9c82ecbe4dcc802feb472607a8c1 |
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