包装材料、辅料对参麦注射液稳定性影响机制  

Stability and degradation mechanism of Shenmai Injection based on packaging materials and excipients

作　　者：李娜 张国琴[2] 刘艺 曹雪晓 任晓亮 王萌[2] LI Na;ZHANG Guoqin;LIU Yi;CAO Xuexiao;REN Xiaoliang;WANG Meng(School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学中药学院,天津301617 [2]天津中医药大学组分中药国家重点实验室,天津301617

出　　处：《中华中医药杂志》2024年第7期3603-3610,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81774149)。

摘　　要：目的:参麦注射液(SMI)收载于国家基本药物目录内,销售量大、临床应用广泛,全面的稳定性研究对于保证其临床用药安全至关重要。方法:通过测定SMI的物理化学性质从长期、加速条件下评价市售SMI的稳定性。采用化学动力学研究不同光照强度和温度影响下人参皂苷的降解情况,超高效液相色谱仪联用四级杆串联飞行时间质谱法(UPLC-Q-TOF-MS)对降解产物进行研究。此外,从包装材料种类、辅料用量角度分析SMI稳定性:定制SMI选用不同吐温-80含量(0.3%、0.5%)和不同包装材料(10 mL SMI分别为低或中硼硅玻璃,50 mL SMI分别为等级Ⅰ硼硅玻璃及等级Ⅱ钠钙玻璃)。结果:仅50 mL SMI的pH值在第12个月和人参皂苷Re+Rg1含量在加速试验第9个月中不符合国家药品监督管理局标准,其他规格SMI的各项指标均在标准范围内。光照对SMI的稳定性无显著性影响,但SMI的pH值及人参皂苷Re、Rg1含量随温度的升高而降低。UPLC-Q-TOF-MS检测到SMI的4种降解产物。10 mL及50 mL SMI均在高等级玻璃及0.5%吐温-80中更稳定。结论:包装材料和药用辅料对SMI的稳定性有显著影响,虽然SMI的包装玻璃不需要任何阻光材料,但建议低温或室温储存条件。Objective:Shenmai Injection(SMI)is included in national essential drugs list,it has voluminous sales and wide application in the clinical field.Research into the comprehensive stability of SMI is essential to ensure it's safety and quality.Methods:Chemical and physical stability was investigated under different influencing factors on market-circulation SMI.Chemical kinetic was adopted to examine the degradation of APIs under different stress conditions(ultraviolet light and high temperature).The degradation products of ginsenosides in SMI were determined by UPLC-Q-TOF-MS.In addition,the stability of SMI was analyzed from the perspective of packaging materials and excipients dosage:Different contents of Tween-80(0.3%,0.5%)were selected for customizing SMI,and different packaging materials(low or medium borosilicate glass for 10 mL SMI,Grade Ⅰ borosilicate glass or Grade Ⅱ soda-lime glass for 50 mL SMI)were used.Results:Only the pH value in the 12th month and concentration(ginsenosides Re+Rg1)in the 9th month of 50 mL SMI did not meet the criteria of the NMPA under accelerated test,while the other specification of SMI remained stable within the criteria.Light irradiation had minimal infuence on the stability of SMI,whereas the content of ginsenosides Re,Rgl and the pH value of SMI decreased as the temperature increased.Four degradation products of SMI were discovered by UPLC-Q-TOF-MS.Both 10 mL and 50 mL SMI were more stable in highergrade glass and 0.5%tween-80.Conclusion:Packaging materials and pharmaceutical excipients have a significant impact on the stability of SMI.Although the packaging glass for SMI did not require any light-blocking material,a low or room-temperature storage condition is suggested.

关 键 词：参麦注射液 药物稳定性 药用包装材料 药用辅料 降解 机制 

分 类 号：R283.6[医药卫生—中药学]