[关键词]
[摘要]
目的 建立测定含麦冬注射液中麦冬皂苷D(OPD)和麦冬皂苷D'(OPD')含量的UPLC-MS/MS方法,评价不同厂家不同批次该注射液的质量的均匀性,为该药临床的安全性评估提供实验依据。方法 色谱采用ACQUITY UPLC HSS T3C18色谱柱(100 mm×2.1 mm,1.7 μm);流动相为0.1%甲酸水(A)-乙腈(B),梯度洗脱;体积流量为0.3 mL/min;进样量为2 μL;质谱采用电喷雾离子源(ESI),负离子检测模式(-),通过多反应监测(MRM)同时对注射液中OPD和OPD'进行定量分析。结果 该注射液中OPD和OPD'在50~10 000 ng/mL线性关系均良好,r均大于0.995 7;专属性,精密度,重复性和稳定性良好。结论 不同厂家注射液样本之间存在一定的质量差异,同一样本中OPD和OPD'以一定比例共存;OPD和OPD'混合给药对红细胞的溶血作用远高于OPD'单独给药,OPD'最高理论平均血药浓度虽未达溶血率浓度警戒线,但临床使用仍可能具有一定风险并对机体产生不良反应,应给予高度重视。
[Key word]
[Abstract]
Objective To establish a simultaneous quantitative analytical method of ophiopogonin D (OPD) and ophiopogonin D' (OPD') in the tested sample contains Ophiopogon japonicas based on ultra-high performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS), assessed of the quality homogeneity of different factory and different batches injections, to provide the data reference for its clinical safety assessment from a hemolytic perspective around the OPD' toxic effects. Method The chromatographic separation was performed on an ACQUITY UPLC HSS T3 C18 column (100 mm×2.1 mm,1.7 μm) with a gradient elution of 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min, and the injection volume was 2 μL. The two components were detected using an electrospray ionization source in negative ionization mode (ESI-) and quantified by multiple reaction monitor (MRM) scanning at the same time. Result The OPD and OPD' both had good linear relationship in range of 50-10 000 ng/mL, the value of "r" was all more than 0.995 7, the specificity, linearity, precision, repeatability, stability and durability of the method were all good. Conclusion The qualities of different factory of the injection have differences in various degrees, OPD and OPD' co-exist in a certain proportion in the same sample, though the theory highest average blood drug concentration not a cordon of hemolysis rate, clinical application still likely to have a certain risk and adverse effects on the body which should be given high attention.
[中图分类号]
R282.71;R965.3
[基金项目]
国家科技重大专项(2015ZX09501004)