Zhu Li, Teng Xu, Duan Yu, Zhang Xia, Xie Jingxin, Xu Mingzhe, Yin Lihui
Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing 100029, China.
Department of Laboratory Medicine, Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.
Pharmaceutics. 2024 Jun 25;16(7):858. doi: 10.3390/pharmaceutics16070858.
Dezocine, which is well-known as an analgesic, had about 45% share of the Chinese opioid analgesic market. Since drug products containing impurities could bring serious health consequences, it was important to control the generation of impurities and degradation products in the dezocine product. In this study, two kinds of photodegradation products (i.e., degradation product 1 and degradation product 2) in the dezocine injection were isolated using high-performance liquid chromatography. The possible structures of the photodegradation products were identified using both high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. In addition, the possible generation mechanism showed that degradation product 1 was the oxidation product of dezocine, and degradation product 2 was the coupled dimer of dezocine. Finally, we found that the degradation rate of dezocine increased with the increase in light intensity. Moreover, the degradation of dezocine easily occurred under ultraviolet light in comparison with visible light. A deeper insight into the generation of the photodegradation products in the dezocine injection would directly contribute to the safety of drug therapy based on the dezocine injection by minimizing the degradant/impurity-related adverse effects of drug preparations.
地佐辛作为一种镇痛药,在中国阿片类镇痛药市场中占有约45%的份额。由于含有杂质的药品可能会带来严重的健康后果,因此控制地佐辛产品中杂质和降解产物的产生非常重要。在本研究中,采用高效液相色谱法分离了地佐辛注射液中的两种光降解产物(即降解产物1和降解产物2)。利用高分辨率质谱和核磁共振光谱确定了光降解产物的可能结构。此外,可能的生成机制表明,降解产物1是地佐辛的氧化产物,降解产物2是地佐辛的偶联二聚体。最后,我们发现地佐辛的降解速率随光照强度的增加而增加。而且,与可见光相比,地佐辛在紫外光下更容易发生降解。深入了解地佐辛注射液中光降解产物的产生,将通过最大限度地减少药物制剂中降解产物/杂质相关的不良反应,直接有助于基于地佐辛注射液的药物治疗的安全性。