药用弹性体密封件中3种秋兰姆类硫化促进剂的定量分析与风险评估  

Quantitative Analysis and Risk Assessment of 3 Thiuram Vulcanization Accelerators in Pharmaceutical Elastomeric Seals

作　　者：夏双双 谢舒婷 陈岚[1] 王蓉佳 蔡荣 XIA Shuangshuang;XIE Shuting;CHEN Lan;WANG Rongjia;CAI Rong(School of Materials and Chemistry,University of Shanghai for Science and Technology,Shanghai 200093,China;Shanghai Food and Drug Packaging Material Control Center,Shanghai 201203,China)

机构地区：[1]上海理工大学材料与化学学院,上海200093 [2]上海市食品药品包装材料测试所,上海201203

出　　处：《理化检验（化学分册）》2024年第1期9-14,共6页Physical Testing and Chemical Analysis(Part B:Chemical Analysis)

摘　　要：提出了超高效液相色谱-串联质谱法同时测定药用弹性体密封件中二硫化四甲基秋兰姆(TMTD)、二硫化四乙基秋兰姆(TETD)和二硫化四丁基秋兰姆(TBTD)含量的方法,并对其是否会与亚硝酸盐反应生成N-亚硝胺类致癌物进行了风险评估。称取1.00 g剪碎后的药用弹性体密封件样品,加入甲醇10 mL,超声提取40 min,提取液和甲醇洗涤液合并后经0.45μm微孔滤膜过滤,采用超高效液相色谱-三重四极杆质谱仪测定滤液中TMTD、TETD和TBTD的含量。以Eclipsepluse C_(18)色谱柱为固定相,以0.1%(体积分数)甲酸溶液-甲醇体系为流动相进行梯度洗脱;采用电喷雾离子源正离子模式和多反应监测模式进行质谱分析,外标法定量。结果表明:3种秋兰姆类硫化促进剂的质量浓度在一定范围内与峰面积呈线性关系,检出限(3S/N)为0.02~0.03 mg·kg^(-1);按照标准加入法对阴性样品进行加标回收试验,回收率为80.9%~103%,测定值的相对标准偏差(n=6)为2.4%~6.3%;方法用于6批实际样品分析,其中3批样品检出TETD,检出量为1.86~2.55 mg·kg^(-1),TMTD和TBTD均未检出;在酸性条件下,将上述3批阳性样品提取液与亚硝酸钠溶液进行反应,结果均检出N-亚硝基二乙胺,检出量为0.0190~0.0201 mg·kg^(-1),不符合法规要求,说明药用弹性体密封件产生N-亚硝胺类化合物的风险较高。A method for the simultaneous determination of tetramethylthiuram disulfide(TMTD),tetraethyl thiuram disulfide(TETD)and tetrabutylthiuram disulfide(TBTD)in pharmaceutical elastomeric seals by ultra-high performance liquid chromatography-tandem mass spectrometry was proposed,and risk assessment was conducted on whether they could react with nitrite to form N-nitrosamine carcinogens.The cut pharmaceutical elastomeric seal sample(1.00 g)was taken,and 10 mL of methanol was added for ultrasonic extraction for 40 min.The extract and methanol washing solution were combined and filtered by 0.45μm microporous filter membrane,and TMTD,TETD and TBTD in the filtrate were determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometer.Gradient elution was performed on Eclipsepluse C_(18)column as the stationary phase and 0.1%(volume fraction)formic acid solution-methanol system as the mobile phase.Electrospray ion source with positive ion mode and multiple reaction monitoring mode were used for mass spectrometry analysis,and external standard method was used for quantitative determination.It was shown that linear relationships between the mass concentrations and the peak areas of 3 thiuram vulcanization accelerators were kept in definite ranges,with detection limits(3S/N)in the range of 0.02-0.03 mg·kg^(-1).Test for recovery was made on the negative sample by the standard addition method,giving results in the range of 80.9%-103%,with RSDs(n=6)of the determined values ranged from 2.4%to 6.3%.The method was used to analyze 6 batches of actual samples,in which TETD was detected in 3 batches of samples,with detected amounts in the range of 1.86-2.55 mg·kg^(-1),and TMTD and TBTD were not detected.The above 3 batches of positive sample extracts were reacted with sodium nitrite solution under acidic condition,and the detected amounts of N-nitrosodiethylamine were in the range of 0.0190-0.0201 mg·kg^(-1),which did not meet the regulatory requirements,indicating that the risk of N-nitrosamines produc

关 键 词：药用弹性体密封件 超高效液相色谱-串联质谱法 秋兰姆类硫化促进剂 N-亚硝胺类化合物 

分 类 号：O657.63[理学—分析化学]