电感耦合等离子体质谱法测定盐酸头孢卡品酯颗粒中9种元素杂质的含量  

Determination of 9 Elemental Impurities in Cefcapene Pivoxil Hydrochloride Granules by Inductively Coupled Plasma Mass Spectrometry

作　　者：朱俐[1] 赵瑜[1] 肖超强 许明哲[1] 尹利辉[1] ZHU Li;ZHAO Yu;XIAO Chaoqiang;XU Mingzhe;YIN Lihui(National Medical Products Adminsitration Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Institutes for Food and Drug Control,Beijing 102629,China;Beijing Diane High Tech Children′s Drug Research Institute Co.,Ltd.,Beijing 100050,China)

机构地区：[1]中国食品药品检定研究院国家食品药品监督管理局化学药品质量研究与评价重点实验室,北京102629 [2]北京达因高科儿童药物研究院有限公司,北京100050

出　　处：《理化检验（化学分册）》2022年第5期512-516,共5页Physical Testing and Chemical Analysis(Part B:Chemical Analysis)

摘　　要：由于头孢卡品酯的理化性质及其颗粒制剂包含很多难溶的辅料,为准确测定盐酸头孢卡品酯颗粒中镉、铅、砷、汞、钴、钒、镍、钼、铬等9种元素杂质的含量,尤其是挥发性元素汞,需要对样品进行络合和稳定性处理。以6 mL硝酸、1.5 mL盐酸、0.1 mL氢氟酸为消解酸,于180℃微波消解50 mg盐酸头孢卡品酯颗粒样品30 min;消解结束后,反复赶酸,再用体积比为0.1∶100的氢氟酸和盐酸-硝酸-水(体积比为1∶4∶95)的混合液定容至50 mL,采用电感耦合等离子体质谱法测定样品中9种元素杂质的含量,内标法定量。结果显示:9种元素杂质的质量浓度在一定范围内与其对应的响应值与内标响应值的比值呈线性关系,检出限(3s/k)为0.001~0.070μg·L^(-1);对6份同一加标样品溶液进行测定,9种元素杂质测定值的相对标准偏差为2.9%~5.1%;对实际样品进行加标回收试验,回收率为82.0%~104%。方法用于实际样品分析,9种元素杂质的含量均低于元素杂质指导原则规定的允许浓度限值。Due to the physical and chemical properties of cefcapene pivoxil and its granulars preparation containing many insoluble excipients,in order to accurately determine the contents of 9 elemental impurities(Cd,Pb,As,Hg,Co,V,Ni,Mo and Cr)in the cefcapene pivoxil hydrochloride granules,especially volatile element Hg,it was necessary to conduct complexation and stability treatment of the sample.6 mL of nitric acid,1.5 mL of hydrochloric acid and 0.1 mL of hydrofluoric acid were used as the digestion acid,and 50 mg of cefcapene pivoxil hydrochloride granules sample was digested by microwave at 180℃for 30 min.After digestion,the acid was removed repeatedly,and then the volume of the sample solution for test was made up to 50 mL with mixed solution(volume ratio of 0.1∶100)of hydrofluoric acid and hydrochloric acid-nitric acid-water at volume ratio of 1∶4∶95.Inductively coupled plasma mass spectrometry was used for the determination of 9 elemental impurities in the sample,and internal standard method was used for quantitative analysis.As shown by the results,linear relationships between values of mass concentration of 9 elemental impurities and response value ratio of analytes to internal standard were kept in definite ranges,with detection limits(3s/k)in the range of 0.001-0.070μg·L^(-1).RSDs of the determined values of 9 elemental impurities for 6 sample solutions with the same spiking amount were in the range of 2.9%-5.1%.Recovery test was made on substantial sample by standard addition method,giving results of recovery in the range of 82.0%^(-1)04%.This method has been applied to the analysis of substantial samples,the contents of 9 elemental impurities were all below the allowable concentration limits from guideline for elemental impurities.

关 键 词：电感耦合等离子体质谱法 盐酸头孢卡品酯颗粒 元素杂质 

分 类 号：O657.63[理学—分析化学]