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. 2022 Jul 8;12(1):11665.
doi: 10.1038/s41598-022-15625-5.

Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods

Mei-Ling Chen  1 , Hong-Xia Xu  1 , Wei-Feng Yuan  1 , Sui-Hong Zhao  1 , Xue Li  1 , Lan-Xin Zhu  1 , Zong-Yong Shen  1 , Yu-Jing Liu  1 , Ming-Juan Wang  2 , Ang Ma  1 , Jos Hoogmartens  3 , Erwin Adams  4
Affiliations

Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods

Mei-Ling Chen et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Proposed photolytic rearrangement pathway of metronidazole to N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide–.
Figure 2
Figure 2
MS spectrum of the major photodegradant of metronidazole. ([M + H]+ m/z 172.17, [M + Na]+ m/z 194.19, [M + K]+ m/z 210.18; and characteristic product ions at m/z 154.12 and m/z 88.13).
Figure 3
Figure 3
UV spectrum of photolytic degradant of metronidazole.
Figure 4
Figure 4
Comparison of chromatograms for light stressed metronidazole in solution (5000 lx, 24 h), with detection at 230 nm and 315 nm, respectively, by LC-PDA experiments.
See this image and copyright information in PMC

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