基于序贯分析策略的丹红注射液与临床常用输液溶媒配伍稳定性及安全性评价

Stability and safety evaluation of Danhong injection with different clinical solvents based on sequential analysis

目的:基于“理化性质-主要成分含量-指纹图谱相似度-类过敏反应”的序贯分析策略,评价丹红注射液与临床常用输液溶媒0.9%氯化钠注射液和5%葡萄糖注射液在不同配伍条件下溶液的稳定性及安全性。方法:根据临床使用情况,将丹红注射液与0.9%氯化钠注射液或5%葡萄糖注射液分别按20 mL:100 mL、30 mL:100 mL、40 mL:100 mL和30 mL:250 mL、40 mL:250 mL的比例进行配伍,在室温条件下10 h内,分别观察和检测各溶液在配伍后不同时间点的性状、渗透压、不溶性微粒和pH;测定溶液在配伍后不同时间点的各主要成分含量;计算配伍后不同时间点各溶液HPLC指纹图谱和^(1)H NMR指纹图谱的相似度;采用RBL-2H3细胞脱颗粒体外类过敏反应检测体系,评价各配伍溶液的安全性。结果:配伍10 h内溶液性状、渗透压、不溶性微粒含量、pH无明显变化,主要成分含量无显著差异,HPLC和1H NMR指纹图谱均有良好的相似度,且配伍溶液无明显致RBL-2H3细胞脱颗粒作用。结论:本研究从物理、化学、生物角度综合评价,表明在30 mL:250 mL~40 mL:100 mL浓度范围内,丹红注射液与0.9%氯化钠注射液或5%葡萄糖注射液在配伍10 h内溶液均有良好的稳定性和安全性,可为临床使用提供参考。

Objective:Based on a sequential analysis method of“physicochemical properties-main component content-fingerprint similarity-anaphylactoid reaction”,the stability and safety of Danhong injection with commonly used clinical solvents 0.9%sodium chloride and 5%glucose injections were evaluated.Methods:According to the clinical application,Danhong injection was mixed with 0.9%sodium chloride injection or 5%glucose injection in the ratios of 20 mL:100 mL,30 mL:100 mL,40 mL:100 mL and 30 mL:250 mL,40 mL:250 mL,respectively.Then,they were placed at room temperature within 10 h.The properties,osmotic pressure,insoluble particles and pH value in the solutions were observed or measured at different time points.The contents of the main components at different time points were determined.The HPLC and~1H NMR fingerprints at different time points were analyzed by similarity evaluation.The in vitro anaphylactoid reaction assay of RBL-2H3 cell degranulation was used to evaluate the safety of the mixture solutions.Results:The properties,osmotic pressure,insoluble particles and pH value of solutions were stable within 10 h after mixing,and there was no significant difference in the contents of the main components.The HPLC and^(1)H NMR fingerprints showed good similarity,and the mixture solutions didn't induce obvious degranulation in RBL-2H3 cells.Conclusion:In this study,the comprehensive evaluation from the physical,chemical and biological perspectives showed that in the concentration range of 30 mL:250-40 mL:100 mL,Danhong injection combined with 0.9%sodium chloride injection or 5%glucose injection had good stability and safety within 10 h,which provides evidences for the clinical practice.