磷酸奥司他韦干混悬剂中杂质谱解析及辅料降解杂质分析

Analysis of Impurity Spectrum and Degradation of Impurities in Oseltamivir Phosphate Oral Suspension

关键词:  磷酸奥司他韦  杂质解析  未知杂质  二维液相色谱串联质谱法

Key words:  oseltamivir phosphate  impurities analysis  unknown impurity  2D-LC-MS/MS

摘要:

目的 对磷酸奥司他韦干混悬剂中一个未知杂质进行结构鉴定、合成和分析，作为已知杂质控制。方法 通过二维液相色谱-质谱（2D-LC-MS/MS）推导未知杂质的结构，根据产品的处方工艺确定杂质来源，并采用定向合成的方式获得杂质单体。采用2D-LC-MS/MS、核磁共振、红外、紫外、热重分析等技术确证杂质的结构，最后采用HPLC对杂质进行分析方法验证。结果 确证该杂质为奥司他韦与辅料山梨醇反应生成的，杂质与奥司他韦的校正因子为1.5。结论 将该杂质命名为杂质I，作为已知杂质定入标准控制，按照自身对照加校正因子法计算杂质含量。

Abstract:

OBJECTIVE To identify, synthesize and analyze the structure of an unknown impurity exceeding the identification threshold in oseltamivir phosphate oral suspension. Set the impurity as known impurity control. METHODS The unknown impurity structure was proposed based on the data of two-dimensional liquid chromatography-mass spectrometry(2D-LC- MS/MS). According to the proposed impurity structure, it was attributed to the formulation process of the product. The impurity reference standard was synthesized successfully, and confirmed by using 2D-LC-MS/MS, NMR, IR, UV and TGA. Finally, the impurity analytical method was established with HPLC. RESULTS It was confirmed that the impurity was produced in a reaction between oseltamivir and the sorbitol. The impurity's correction factor was 1.5. CONCLUSION The impurity is set as a known impurity into the quality control and is named as impurity I. The impurity assay is calculated by the self-control associated with correction factor method.