摘要
目的采用高效液相色谱法开展注射用腺苷钴胺有关物质研究,并对相关杂质进行质谱分析和毒性预测。方法高效液相色谱法测定,色谱条件是用十八烷基硅烷键合硅胶为填充剂色谱柱,检测波长为260 nm,柱温35℃,进样体积10μL,0.01 mol·L^(-1)酸铵溶液(冰醋酸调剂p H值至4.0)为流动相A,甲醇为流动相B,进行梯度洗脱。采用所建方法对105批注射用腺苷钴胺开展有关物质评价。含量≥0.1%的未知杂质采用高效液相色谱串联四极杆静电场轨道阱高分辨质谱(HPLC-QE-MS)扫描并对未知杂质开展基因毒性预测。结果所建方法各杂质峰能与主峰有效分离,检测限为1.497×10^(-4)mg·mL^(-1),对检测方法进行了方法学验证,结果符合药典要求。结论所建方法测定专属性强,准确度高,重复性好,能够有效获得全面的杂质信息,适用于注射用腺苷钴胺的杂质检查与控制。
Objective High performance liquid chromatography was used to study the related substances of adenosine cobalt amine for injection,and mass spectrometry analysis and toxicity prediction were performed on the related impurities.Methods Determination by high-performance liquid chromatography,the chromatographic conditions were using octadecylsilane bonded silica gel as the filling agent in the chromatographic column,with a detection wavelength of 260 nm,a column temperature of 35℃,and an injection volume of 10μL.0.01 mol·L^(-1)ammonium acetate solution(adjusted to pH 4.0 with glacial acetic acid)was used as mobile phase A,and methanol was used as mobile phase B for gradient elution.The established method was used to evaluate the related substances in 105 batches of adenosine cobalt amine for injection.Unknown impurities with a content of≥0.1%were scanned by high-resolution mass spectrometry and genotoxicity prediction was performed on the unknown impurities.Results The impurity peaks of the established method were effectively separated from the main peak,with a detection limit of 1.497×10^(-4) mg·mL^(-1).The methodological validation of the detection method was conducted,and the results met the requirements of the pharmacopoeia.Conclusion The established method has strong specificity,high accuracy,good repeatability,and can effectively obtain comprehensive impurity information.It is suitable for impurity detection and control of adenosine cobalt amine for injection.
作者
郝钢
韩峰
周刚
颜皓
武星
李旭扬
候海玲
宁霄
汪祺
崔黎
HAO Gang;HAN Feng;ZHOU Gang;YAN Hao;WU Xing;LI Xuyang;HOU Hailing;NING Xiao;WANG Qi;CUI Li(Inner Mongolia Institute of Drug Inspection,Hohhot,Inner Mongolia 010020,China;Institute for Food and Cosmetics Testing,National Institutes for Food and Drug Control,Beijing 100050,China;Institute for Control of Chinese Traditional Medicine and Ethnic Medicine,National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《中国药物警戒》
2023年第12期1339-1345,共7页
Chinese Journal of Pharmacovigilance
基金
国家重点研发计划(2021YFC2401100)。
关键词
注射用腺苷钴胺
有关物质
高效液相色谱
质谱
杂质
方法学
adenosine cobalt amine for injection
related substances
high-performance liquid chromatography
mass spectrometry
impurity
methodology
作者简介
郝钢,男,硕士,副主任药师,药理学与药物安全性评价;并列第一作者:韩峰;通信作者:崔黎,女,本科,主任药师,药物质量标准研究。E-mail:413647638@qq.com;共同通信作者:汪祺。
