盐酸氨溴索注射液中24种元素杂质测定及包装系统相容性考察

Determination of 24 Element Impurities in Ambroxol Hydrochloride Injection and Compatibility of Packaging System

为建立24种元素杂质电感耦合等离子体质谱法(ICP-MS),用于考察盐酸氨溴索注射液在存储期间与中硼硅玻璃安瓿瓶的相容性并进行安全性评估。将药液以2%硝酸溶液稀释后,通过在线加入内标钪(Sc)、铟(In)、铋(Bi)、锗(Ge)元素,来校准基质效应和消除干扰。结果表明,3批新生产的盐酸氨溴索注射液(0个月)24种元素杂质检测结果均符合分析评价阈值要求。同批次在加速条件下放置6个月的样品检测,仅硼(B)、铝(Al)、硅(Si)、钡(Ba)4种元素杂质有增长趋势,B从3%限度值增长到12%限度值,Al从5%限度值增长到30%限度值,Si从48%限度值增长到80%限度值,Ba从5%限度值增长到15%限度值。硅/铝及硅/硼浓度比值较对应同批次0个月的样品均有明显变化,说明该方法灵敏度高,线性范围宽,准确度高,重复性好,可用于药液与中硼硅玻璃安瓿包装系统相容性的研究。由加速6个月的研究结果可知,中硼硅玻璃安瓿与盐酸氨溴索注射液间有相互作用,但在加速条件下存放6个月内,元素杂质迁移量符合分析评价阈值要求,说明本品与包装系统相容性良好。

In order to establish 24 element impurities inductively coupled plasma masspetrometry(ICP-MS),the study determines the compatibility of ambroxol hydrochloride injection in storage and borosilicate glass ampoule,and does security evaluation.After physic liquor attenuation with 2%saltpeter solution,Sc,In,Bi and Ge are added to calibrate matrix effect and eliminate interference.The results show that the test results of 24 element impurities of 3 new batches of ambroxol hydrochloride injection(0 month)meet the requirements of analysis evaluation.After 6 months,B,Al,Si and Ba element impurities in the test samples of the same batch under acceleration condition increase.Limit value of B increases from 3%to 12%,Al increases from 5%to 30%,Si increases from 48%to 80%,and Ba increases from 5%to 15%.Concentration values of Si/Al and Gi/B change significantly compared with the samples of the same batch 0 month.This indicates that the method has high accuracy,linearity range is wide,accuracy rate is high,and repeatability is good,so it can be used in the research of compatibility of physic liquor and borosilicate glass ampoule packaging system.The research results of acceleration after 6 months show that there is interaction between borosilicate glass ampoule and ambroxol hydrochloride injection,but the volume of migration of element impurities meets the requirements of the analysis and evaluation of threshold value under acceleration in 6 months,indicating that there is good compatibility between the sample and packaging system.