Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods
Mei-Ling Chen1, Hong-Xia Xu1, Wei-Feng Yuan1
1Beijing Sun-Novo Pharmaceutical Research Company Ltd, Yunguyuan, No.79 Shuangying West Road, Changping District, Beijing, 102200, People's Republic of China.
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.
Insights
Metronidazole degrades under light, forming a specific compound. Current tests miss this photolytic impurity, but an improved liquid chromatography method can now detect it.
Area of Science:
- Pharmaceutical analysis
- Photochemistry
Background:
- Metronidazole is susceptible to photodegradation in aqueous solutions.
- Existing compendial methods fail to detect photolytic degradants.
Purpose of the Study:
- To identify and quantify metronidazole photolytic degradants.
- To develop and validate an improved analytical method for metronidazole impurity profiling.
Main Methods:
- Liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS).
- Proton nuclear magnetic resonance (1H-NMR) spectroscopy for structural verification.
- Development and validation of an optimized liquid chromatography (LC) method.
Main Results:
- Identified N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide as a photolytic degradant of metronidazole.
- Demonstrated the inability of current compendial tests to detect this impurity.
- Developed a validated LC method with enhanced separation using a 230 nm detection wavelength and optimized mobile phase.
Conclusions:
- Metronidazole photodegradation products are not detected by current standard tests.
- An improved LC method is necessary for accurate impurity profiling of metronidazole, especially concerning photolytic degradation.
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