目的: 根据ICH Q3D最新要求,建立同时测定注射用头孢美唑钠中10种元素杂质的方法。方法: 样品经直接溶解并稀释后采用电感耦合等离子质谱分析,以硒(Se)、锗(Ge)、碲(Te)、镥(Lu)为内标,等离子功率1 550 W,载气流量1.09 L·min-1。结果: 10种元素线性均良好(r均>0.999),检测限为0.000 2~0.059 ng·mL-1,各浓度点平均回收率为90%~110%(n=3),重复性RSD为4%~10%(n=6)。5家企业12批样品中有3批测得镍(Ni)(0.1 μg·mL-1),其中1批测得锂(Li)(0.1 μg·mL-1),不同厂家的注射用头孢美唑钠中10种元素杂质含量均符合ICH规定。结论: 本文应用的方法简单快速,灵敏度高,准确性好,可用于注射用头孢美唑钠中元素杂质的质量控制。
Objective: To develop a method for simultaneous determination of 10 elemental impurities in cefmetazole sodium for injection according to the latest requirement of ICH Q3D. Methods: Samples were analyzed after direct dissolved and dilution by inductively coupled plasma mass spectroscopy (ICP-MS), with selenium (Se), germanium (Ge), tellurium (Te), and lutetium (Lu)as internal standards. RF power was set at 1 550 W and carrier gas was set at 1.09 L·min-1. Results: The linear relationship for all elemental impurities were good(r>0.999), with a detection limit of 0.000 2-0.059 ng·mL-1. The average recovery rate at each concentration point was 90%~110% (n=3), and the RSD were 4%-10% (n=6). Nickel (Ni) were detected at 0.1 μg·mL-1 in 3 out of 12 batches of samples from five companies, and lithium (Li) was detected at 0.1 μg·mL-1 in 1 batche. The contents of 10 elemental impurities in cefmetazole sodium for injection from different manufacturers comply with ICH requirement. Conclusions: The established method was simple, rapid, sensitive, accurate and can be used for the quality control of elemental impurities in cefmetazole sodium for injection.
[1] 张春然,唐克慧.头孢美唑钠质量与稳定性研究[J].国外医药抗生素分册,2005,26(1):5
ZHANG CR, TANG KH. Study on quality and stability of cefmetzole sodium[J].World Notes Antibiot, 2005, 26(1):5
[2] 中华人民共和国药典2020年版. 二部[S]. 2020: 342
ChP 2020.Vol Ⅱ[S]. 2020: 342
[3] USP 43-NF 36. Vol Ⅰ[S]. 2020: 823
[4] JP 17. Vol Ⅰ[S]. 2017: 628
[5] CHAHROUR O, MALONE J, COLLINS M, et al. Development and validation of an ICP-MS method for the determination of elemental impurities in TP-6076 active pharmaceutical ingredient (API) according to USP (232)/(233)[J].J Pharm Biomed Anal, 2017, 145:84
[6] 顾霄,朱思琪,郑金琪.葡萄糖酸钙注射液中24种元素杂质测定方法的建立[J].药物分析杂志,2020,40(2):278
GU X, ZHU SQ, ZHENG JQ. A method for the determination of 24 element impurities in calcium gluconate injection according to ICH requirement[J].Chin J Pharm Anal, 2020, 40(2):278
[7] ICH Q3D. Guideline for Elemental Impurities [S].2018
[8] FISCHER L, ZIPFEL B, KOELLENSPERGER G, et al. Flow injection combined with ICP-MS for accurate high throughput analysis of elemental impurities in pharmaceutical products according to USP [J].J Pharm Biomed Anal, 2014, 95:121
[9] MULLER ALH, OLIVERRA JSS, MELLO PA, et al. Study and determination of elemental impurities by ICP-MS in active pharmaceutical ingredients using single reaction chamber digestion in compliance with USP requirements[J].Talanta, 2015, 136:161
[10] 彭双,杨海源,张敏娟,等.ICP-MS大测定小儿氨酚黄那敏颗粒中重金属及有害元素的含量[J].中国药房,2021,32(18):2218
PENG S,YANG HY,ZHANG MJ, et al. Determination of heavy metals and harmful elements in paracetamol artifical cow-bezoar and chlorphenamine maleate granules by ICP-MS[J]. China Pharm, 2021, 32(18):2218
[11] MENOUTIS J, PARISI A, VERMA N. Study of the use of axial viewed inductively coupled plasma atomic emission spectrometry with ultrasonic nebulization for the determination of select elemental impurities in oral drug products[J].J Pharm Biomed Anal, 2018, 152:12
[12] 徐文峰,金鹏飞,徐硕,等.电感耦合等离子体质谱在药物分析中的应用[J].药物分析杂志,2017,37(12):2123
XU WF, JIN PF, XU S, et al. Application of ICP-MS in pharmaceutical analysis[J].Chin J Pharm Anal, 2017, 37(12):2123
[13] 梁建谋,王芸.ICP-MS同时测定鱼肝油中21种重金属元素残留量[J].中国现代应用药学,2021,38(10):1161
LIANG JM, WANG Y. Simultaneous determination of twenty-one trace heavy metal elements in cod liver oil using ICP-MS[J].Chin Mod Appl Pharm, 2021, 38(10):1161
[14] HOECKEA KV, CATRYB C, VANHAECKEA F. Determination of elemental impurities in leachate solutions from syringes using sector field ICP-mass spectrometry [J].J Pharm Biomed Anal, 2013, 77:139
[15] USP 43-NF 36. Vol Ⅳ[S]. 2020: 6151