奥利司他原料药制备过程中的杂质分析

Analysis of Impurities in Preparation Process of Orlistat Raw Material Drug

目的采用高效液相色谱(HPLC)法分析奥利司他在发酵、制备和包装过程中产生或引入的杂质,为制订药品生产过程控制质量标准提供数据和参考。方法色谱柱为Agilent C18柱(250 mm×4.6 mm,2.5μm),流动相为乙腈-水(80∶20),UV检测波长为195 nm,流速为1.2 mL/min。结果发酵过程中微生物代谢产物是杂质的主要来源;而奥利司他在制备过程中容易发生氧化、水解和受热降解而产生不同的杂质,特别是受酸或碱作用会发生显著的降解;由于奥利司他残留溶剂的作用,采用不同的包装材料也会引入杂质。结论在奥利司他生产过程中,应从生产工艺、原辅料和包装材料各个方面进行严格控制,才能有效控制杂质的含量。

Objective To adopt the HPLC method to analyze the impurities generated or induced in the fermentation, preparation and packaging processes of orlistat. Methods The chromatographic analysis was performed on the Agilent Cls column （250 mm ×4.6 ram, 2.5 μm） with the mobile phase of acetonitrile-water （80：20）.The detective wavelength was 195 nm. The flow rate was 1.2 mL/min. Results The microbial metabolic products generated during the fermentation process are the main source of impurities;orlistat is apt to oxi- dize,hydrolyze and thermally degrade to generate different uncertain impurities,especially develope remarkable degradation by acidolysis and alkalization. Conclusion Due to the action of orlistat residual solvent,adopting different packing materials also introduce the impurities.