目的:建立测定新型冠状病毒灭活疫苗(Vero细胞)铝含量的电感耦合等离子体质谱(ICP-MS)法。方法:以钪为内标元素,用2%硝酸溶液稀释样品,采用ICP-MS法进行测定,选择碰撞池模式(KED),射频功率1.6 kW,等离子体流量14.99 L·min-1,雾化气流速1.02 L·min-1,辅助气流量1.20 L·min-1,蠕动泵转速:-35 r·min-1,氦气流速5 mL·min-1,积分时间2 s,跳峰模式,重复次数3次。并进行相关的方法学验证。结果:铝元素质量浓度在0~2 mg·L-1范围内线性关系良好(r=0.999 9);检测限为0.073 9 μg·L-1,定量限为0.246 2 μg·L-1;精密度RSD(n=8)为0.70%;重复性RSD(n=8)为3.0%;平均回收率(n=8)为106.7%,RSD为2.1%。结论:ICP-MS法操作简单、快速,准确度和重复性好,可用于新冠病毒灭活疫苗(Vero细胞)的铝含量测定。
Objective: To establish a method for the determination of aluminum element in COVID-19 inactivated vaccine (Vero Cell) by inductively coupled plasma mass spectrometry. Methods: Scandium was as the internal standard element and the sample was diluted with 2% nitric acid solution. ICP-MS method was used for determination. The collision cell mode (KED) was selected, with a radiofrequency power of1.6 kW, a plasma gas flow rate of 14.99 L·min-1, a nebulizer gas flow rate of 1.02 L·min-1, an auxiliary gas flow rate of 1.20 L·min-1, a peristaltic pump speed of -35 r·min-1, a helium flow rate of 5 mL·min-1, an integration time of 2 s, and a peak-jumping mode with 3 repetitions. The relevant methodological validation was conducted. Results: There was a good linear relationship for aluminum element within the range of 0-2 mg·L-1(r=0. 999 9), the limit of detection was 0.073 9 μg·L-1,the limit of quantifi-cation was 0.246 2 μg·L-1. RSD of precision tests (n=8) was 0.70%. And RSD of repeatability tests (n=8) was 3.0%. The average recovery (n=8) was 106.7% with an RSD of 2.1%. Conclusion: The established ICP-MS method is simple, rapid, accurate and reproducible, and can be used for the determination of aluminum content in the COVID-19 inactivated vaccine (Vero cell).
[1] 国家药品监督管理局.药品注册标准YBS00192021[S]. 2021
National Medical Products Administration (NMPA) Drug registration standard YBS00192021 [S]. 2021
[2] 国家药品监督管理局.药品注册标准YBS00842021[S]. 2021
National Medical Products Administration (NMPA) Drug registration standard YBS00842021 [S]. 2021
[3] 中华人民共和国药典2020年版.三部[S]. 2020:98,143,159
ChP 2020.Vol Ⅲ [S]. 2020:98,143,159
[4] 国家药品监督管理局. 预防用含铝佐剂疫苗技术指导原则及起草说明[S]. 2019-12-09
National Medical Products Administration. Technical guidelines for aluminum-containing adjuvant vaccines for prophylaxis[S]. 2019-12-09
[5] 王晓娟,马锐,曹琰,等. 铝佐剂及佐剂吸附疫苗质量标准的探讨[J]. 中国生物制品学杂志,2019,32(4):485
WANG XJ,MA R,CAO Y, et al. Discussion on the quality standard of aluminum adjuvant and adjuvant adsorbed vaccine[J]. Chin J Biol,2019,32(4):485
[6] 赵晨燕,黄维金. 铝佐剂理化特性及其吸附抗原后产物的质量控制研究进展[J]. 微生物免疫学进展,2018,46(5):86
ZHAO CY,HUANG WJ. Progress on physico-chemical properties of aluminum adjuvant and quality control of related adsorbed antigen preparation[J]. Prog Microbiol Immunol,2018,46(5):86
[7] USP 2023. <1235> Vaccines for human use—General Considerations [S/OL]. (2021-05-01) [2023-03-18]. https://online.uspnf.com/uspnf/document/1_GUID-A0173998-8A54-47AE-9843-F53DFAD988E0_2_en-US
[8] BP 2023. VolⅠ [S]. 2022:122
[9] EP 11.0 VolⅠ [S]. 2022:183
[10] 中华人民共和国药典2020年版.四部[S]. 2020:287,305
ChP 2020.Vol Ⅳ [S]. 2020:287, 305
[11] 陈琼,王璟,石继春,等. ICP-OES法测定13价肺炎球菌结合疫苗中的铝含量[J]. 药物分析杂志, 2015, 35 (11):1995
CHEN Q, WANG J, SHI JC, et al. Determination of aluminum content in 13-valent pneumococcal conjugated vaccine by inductively coupled plasma optical emission spectrometry [J]. Chin J Pharm Anal, 2015, 35 (11): 1995
[12] 王平,张学峰,陈美丽,等. 疫苗中铝含量紫外分光光度测定法的建立及验证 [J]. 中国生物制品学杂志,2021, 34(9): 1094
WANG P, ZHANG XF, CHEN ML, et al. Development and verification of a novel method for determination of aluminium content in vaccine by ultraviolet spectrophotometry [J]. Chin J Biol, 2021, 34(9):1094
[13] 刘锐, 高秀梅,乔敏莎,等. ICP-MS 法测定消渴淸颗粒原料药材中15种重金属和有害元素及其不确定度评估[J]. 药物分析杂志, 2019,39(4): 685
LIU R, GAO XM, QIAO MS, et al. Determination of fifteen heavy metals and harmful elements in raw materials of Xiaokeqing granules by ICP-MS and evaluation of the uncertainty [J]. Chin J Pharm Anal, 2019, 39(4): 685
[14] 邵天舒,周长明,余立,等. ICP-MS法同时测定小牛血去蛋白提取物注射液中14种元素的含量[J]. 中国药房,2019, 30 (14):1902
SHAO TS, ZHOU CM, YU L, et al. Simultaneous determination of 14 elements in deproteinized calf blood extractives injection by ICP-MS [J]. China Pharm, 2019, 30 (14):1902
[15] 安永鹏,杨彦丽,丁轲. ICP-MS和ICP-OES法检测粉条中铝含量的比较研究[J]. 中国食品添加剂,2021, 32(6):108
AN YP, YANG YL, DING K. Comparison of ICP-MS and ICP-OES for detection of aluminum in vermicelli [J]. China Food Add, 2021, 32(6):108
[16] 赵沁,周勤,倪骏,等. 人血白蛋白中铝残留量电感耦合等离子体质谱测定法的优化[J]. 中国药师,2019, 22 (2): 363
ZHAO Q, ZHOU Q, NI J, et al. Determination optimization of aluminum residues in human albumin by inductively coupled plasma mass spectrometry [J]. China Pharm, 2019, 22 (2): 363
