高效液相色谱法同时测定镥[^(177)Lu]氧奥曲肽注射液中两种稳定剂的含量  

Simultaneous Determination of Two Stabilizers Content in Lutetium[^(177)Lu]Oxodotreotide Injection by High-Performance Liquid Chromatography

作　　者：王勇 梁塑 孔祥瑞 李英 范振亚 罗田伟 王宁 付博 马红利 杨柳 李洪玉 WANG Yong;LIANG Su;KONG Xiang-rui;LI Ying;FAN Zhen-ya;LUO Tian-wei;WANG Ning;FU Bo;MA Hong-li;YANG Liu;LI Hong-yu(HTA Co.,Ltd.,Beijing 102413,China;China Atomic Energy Authority Center of Excellence on Nuclear Technology Applications for Engineering and Industrialization of Radiopharmaceuticals,Beijing 102413,China;China National Nuclear Corporation 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]中国核工业集团有限公司放射性药物工程技术研究中心,北京102413

出　　处：《核化学与放射化学》2025年第1期86-92,I0004,共8页Journal of Nuclear and Radiochemistry

摘　　要：为建立高效液相色谱法(HPLC)测定镥[^(177)Lu]氧奥曲肽注射液中稳定剂(龙胆酸、维生素C)的含量,采用十八烷基硅烷键合有机杂化硅胶填充的色谱柱(4.6 mm×250 mm×5μm),以0.82 g/L醋酸钠溶液(用冰醋酸调pH至3.50)和甲醇为流动相,串联紫外-可见分光检测器(检测波长为295 nm)与放射性流量检测器,柱温为25℃,进样体积为5μL,运行20.0 min,1.00 mL/min进行梯度淋洗,可有效地将龙胆酸和维生素C分离。龙胆酸和维生素C分别在0~1.50 g/L和0~30.0 g/L质量浓度范围内线性关系良好,相关系数r分别为1.000和0.998;改变柱温、流速、流动相pH值等色谱条件时,样品溶液中维生素C和龙胆酸含量的相对标准偏差均满足≤2.0%的要求;龙胆酸的回收率满足90%~108%的要求,维生素C回收率满足92%~105%的要求。该方法简便、快速、灵敏、准确,可用于镥[^(177)Lu]氧奥曲肽注射液中龙胆酸和维生素C含量的准确测定,为该类药物的工艺过程优化提供了指导作用。A high-performance liquid chromatography(HPLC)was established for the determination of stabilizer(gentisic acid,vitamin C)content in lutetium[^(177)Lu]oxodotreotide injection.The liquid chromatographic parameters were finally confirmed by the optimization experiments of the chromatographic column,mobile phase,elution gradient and UV wavelength.The chromatographic column(4.6 mm×250 mm×5μm)filled with octadecylsilane bonded organic hybrid silica gel was used,and the mobile phase was 0.82 g/L sodium acetate solution(pH was adjusted to 3.50 with glacial acetic acid)and methanol(gradient elution).The detector system was ultra-violet visible spectroscopic detector(detection wavelength was 295 nm)and radioactive flow detector connnected in series.The column temperature was 25℃,the injection volume was 5μL,the running time was 20.0 min,and the flow rate was 1.00 mL/min with gradient elution.The method can effectively separate gentisic acid and vitamin C,and the resolution meets the requirement of greater than 1.5.The linear ranges of gentisic acid and vitamin C are 0-1.50 g/L and 0-30.0 g/L,respectively.The correlation coefficient r are 1.000 and 0.998,respectively.When the chromatographic conditions of column temperature,flow rate and mobile phase pH are changed,the relative standard deviation(sr)of vitamin C and gentisic acid in the sample solution are 1.62%and 1.16%(n=9)respectively,meet the requirement of less than 2.0%.The sr of the retention and content of gentisic acid in six samples are 0.10%and 0.13%,respectively.The sr of the retention and content of vitamin C in six samples are 0.06%and 0.19%,respectively.The sr of the retention and content of gentisic acid in twelve samples are 0.18%and 0.30%,respectively.The sr of the retention and content of vitamin C in twelve samples are 0.10%and 1.49%,respectively.The above sr results all meet the requirement of less than 2.0%.The rate of recovery of gentisic acid meets the requirement of 90%-108%,and the rate of recovery of vitamin C meets the requirement of 92%-1

关 键 词：高效液相色谱法 镥[^(177)Lu]氧奥曲肽注射液 稳定剂 龙胆酸 维生素C 方法验证 

分 类 号：TQ421.6[化学工程] O657.72[理学—分析化学]