基于聚合物添加剂谱库的缓冲盐中塑料药品包装材料难挥发可溶出物的快速分析方法研究

采用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS),结合基于UNIFI软件建立的174种聚合物添加剂的谱库,实现了塑料药品包装材料中难挥发可溶出物(Extractables)的快速筛查和准确定量。样品经氯仿萃取后,以甲醇和0.1%甲酸水溶液为流动相在CORTECS C18(2.1 mm×100 mm,1.6μm)色谱柱上进行分离,在质谱电喷雾正离子模式下,UPLC-QTOF-MS进行筛查和定量分析。结果表明,浸泡60 d缓冲盐(25℃)中检出4种物质,利用谱库筛查确定其中1种物质是邻苯二甲酸二异癸酯(DIDP),采用外标法定量,测得其溶出量为1.98μg/L;其余3种物质可通过精确质量数、MSE谱图等进行推断定性,利用结构与质量数相近的邻苯二甲酸二环己酯(DCHP)为内标进行定量,3种提取物的总含量为10.80μg/L。利用DIDP进行回收率实验,5,10,20μg/L 3个加标水平的回收率为90.1%~97.1%,相对标准偏差(RSD,n=6)不大于3.7%。该方法快速、准确、灵敏,适用于药品包装材料的安全性考察。

Analysis of Nonvolatile Extractables in Pharmaceutical Packaging Materials in Buffered Saline Based on Polymer Additive Library

A rapid method for the determination of extractables in pharmaceutical packaging materials was developed by ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry(UPLC-QTOF-MS) based on UNIFI software and a polymer additive library.The samples were extracted with chloroform,and then the extractables were separated on a CORTECS C18 (2.1 mm × 100 mm,1.6 μm) column using a binary solvent system composed of methanol and 0.1％ formic acid water solution.Screening and quantitative analysis were accomplished by UPLC-QTOF-MS under positive electrospray ion mode.The results showed that four extractables were detected in buffered saline(25 ℃,60 days).Diisodecyl phthalate(DIDP) was identified by library searching and quantitated by external standard method with a concentration of 1.98 μg/L.The other three extractables were inferred and identified by accurate mass and MSE spectra match,and they were quantitated with dicyclohexyl phthalate(DCHP).The total content of the three compounds was 10.80 μg/L.The recovery analysis was carried out to evaluate the method with DIDP.The results indicated that the recoveries of DIDP ranged from 90.1％ to 97.1％ with relative standard deviation (RSD) no more than 3.7％ (n =6) at three spiked concentration levels(5,10,20 μg/L).The method was rapid,accurate and sensitive,and was suitable for the safety investigation on pharmaceutical packaging materials.