发生器来源的氯化镓[^(68)Ga]溶液杂质研究  

Impurity of Gallium[^(68)Ga]Chloride Solution from Generator

作　　者：吴福海 陈孟毅 王晓明 王春林 孙明月 邱珊珊 周佳骏 秦祥宇 沈浪涛 WU Fuhai;CHEN Mengyi;WANG Xiaoming;WANG Chunlin;SUN Mingyue;QIU Shanshan;ZHOU Jiajun;QIN Xiangyu;SHEN Langtao(HTA Co.,Ltd.,Beijing 102413,China;CAEA Center of Excellence on Nuclear Technology Applications for Engineering and Industrialization of Radiopharmaceuticals,Beijing 102413,China;CNNC Engineering Research Center of Radiopharmaceuticals,Beijing 102413,China)

机构地区：[1]原子高科股份有限公司,北京102413 [2]国家原子能机构核技术(放射性药物工程转化)研发中心,北京102413 [3]中核集团放射性药物工程技术研究中心,北京102413

出　　处：《原子能科学技术》2023年第10期1889-1898,共10页Atomic Energy Science and Technology

基　　金：国防科工局核能开发项目。

摘　　要：镓[^(68)Ga]是PET显像药物中一种重要的正电子核素。为保证镓[^(68)Ga]药物关键原料氯化镓[^(68)Ga]溶液的质量满足高标记率、安全性等要求,本文对发生器来源的氯化镓[^(68)Ga]溶液的杂质进行了研究,建立了杂质的检测方法:氯化镓[^(68)Ga]溶液的放射化学纯度采用放射性薄层色谱(Radio-TLC)检测;氯化镓[^(68)Ga]溶液中的12种元素杂质(铁、锌、砷、镉、汞、铅、钴、镍、钒、锂、铜、锑)采用电感耦合等离子体质谱(ICP-MS)进行检测;氯化镓[^(68)Ga]溶液的放射性核纯度用高纯锗(HPGe)γ能谱检测。根据样品的特性以及用于放射化学杂质、元素杂质、放射性核素杂质检测方法的特点,对所建立的分析方法进行了验证。结果表明,建立的分析方法能准确检测氯化镓[^(68)Ga]溶液的杂质,有效控制其质量。样品杂质含量符合欧洲药典(EP10.0)的质量标准。本文所建立的氯化镓[^(68)Ga]溶液杂质分析方法能为镓[^(68)Ga]药物放射性原料的杂质控制、质量标准建立提供参考。Gallium[^(68)Ga]is an important positron-emitting radionuclide in PET imaging radiopharmaceuticals.In order to ensure that the quality of gallium[^(68)Ga]solution,a key raw material of gallium[^(68)Ga]radiopharmaceuticals,meets the requirements of high labeling efficiency and safety,a detailed study on impurities in gallium[^(68)Ga]solution from the generator was carried out,analytical method for impurity detection was developed and the validation of the methodology was completed.To control radiochemical impurities,radioactive thin-layer chromatography(Radio-TLC)method was used.The effects of key variables such as mobile phase,pH of the mobile phase,and system suitability solution on the test results were studied.After method optimization,iTLC-SG was determined to be the stationary phase,methanol-1 mol/L ammonium acetate(1∶1,V/V,ammonium acetate pH=2.8±0.2)as the mobile phase.In order to control elemental impurities,twelve elements including Fe,Ni,Zn,Sb,Pb,Li,V,Co,Cu,As,Cd,and Hg were determined by inductively coupled plasma mass spectrometry(ICP-MS)method.The radionuclide purity was determined by high-purity germanium(HPGe)γspectroscopy,and theγnuclide impurities such as 68 Ge were controlled.Combined with the properties of the samples and the characteristics of each analytical method,the established analytical methods were validated.The validation included system suitability and resolution,linearity,limit of detection(LOD),limit of quantification(LOQ),accuracy,precision,durability,etc.These validated methods were used to determine impurities in gallium[^(68)Ga]chloride solutions.The impurity test results of gallium[^(68)Ga]chloride solution show that the R f of ^(68)Ga 3+is≤0.2,and its radiochemical purity is 99.04%±0.35%(n=3).Its iron content is≤0.5μg/GBq,zinc content is≤0.1μg/GBq,and other elements do not exceed 30%of the PDE limits.Gallium[^(68)Ga]radionuclide purity is more than 99.9%,otherγnuclide impurities are not detected at the first detection.24 hours later,germanium[68 Ge]breakthrough

关 键 词：氯化镓[^(68)Ga]溶液 放射化学纯度 元素杂质 放射性核纯度 杂质研究 

分 类 号：TL92[核科学技术—核燃料循环与材料] R917[医药卫生—药物分析学]