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

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.

TLC–Densitometric Analysis of Selected 5-Nitroimidazoles

“…Verma et al [16] using HPLC found five degradation products in a sample of metronidazole in hydrogen peroxide after 48 h, which is consistent with the results obtained in this work. Chen et al [35] in a sample of metronidazole after photodegradation, using the LC-PDA-MS technique, also found the presence of five of its degradation products. Therefore, the proposed TLC-densitometry method is selective in relation to the analysis of metronidazole.…”

“…Metronidazole Secnidazole The study of the stability of metronidazole, secnidazole, ornidazole, and tinidazole has been the subject of numerous scientific papers . Various analytical techniques were used to analyze the stability of 5-nitroimidazoles: high-performance liquid chromatography (HPLC) [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], ultra-performance liquid chromatography (UPLC) [33,34], liquid chromatography with mass spectrometry (LC-MS) [25], liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) [35], UV- The study of the stability of metronidazole, secnidazole, ornidazole, and tinidazole has been the subject of numerous scientific papers . Various analytical techniques were used to analyze the stability of 5-nitroimidazoles: high-performance liquid chromatography (HPLC) [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], ultra-performance liquid chromatography (UPLC)…”

“…These publications mainly give the amounts of 5-nitroimidazole that remained (not that which was degraded or what percentage was decomposed) under stress conditions. Only in a few publications do the authors indicate to what number of degradation products the tested 5-nitroimidazole is converted [16,[21][22][23][24][25]27,29,35,43,44]. In addition, there are no scientific reports in which the stability of metronidazole, secnidazole, ornidazole, and tinidazole was tested under exactly the same stress conditions and using exactly the same research method.…”