葡萄糖酸钙注射液有关物质测定与高温降解杂质结构鉴定  

Determination of Related Substances of Calcium Gluconate Injection and Thermal Degradation Impurity Identification

作　　者：艾婕 顾霄 AI Jie;GU Xiao(Zhejiang Institute for Food and Drug Control,NMPA Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou 310052,China)

机构地区：[1]浙江省食品药品检验研究院国家药监局仿制药评价关键技术重点实验室,杭州310052

出　　处：《中国现代应用药学》2022年第15期2001-2005,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省基础公益研究计划项目(LGC21H300001)。

摘　　要：目的 建立葡萄糖酸钙注射液有关物质的测定方法,对高温降解杂质[相对保留时间(relative retention time,RRT)4.18]进行结构鉴定。方法 采用HPLC进行有关物质测定,使用XbridgeC8色谱柱(250 mm×4.6 mm,5μm),流动相为含0.1 mol·L^(-1)磷酸氢二钾与1 mmol·L^(-1)四丁基氢氧化铵的混合溶液,用磷酸调节pH值至5.5,检测波长为210 nm。采用HPLC-Q-TOF/MS方法,对RRT 4.18杂质做结构鉴定。结果 有关物质测定方法条件下主成分与杂质分离度良好,RRT4.18杂质鉴定为5-羟甲基-2-糠酸。5-羟甲基-2-糠酸的线性范围为0.18~2.26μg·mL^(-1)(r=0.999 0),检测限为0.06μg·mL^(-1)。结论 建立的方法能准确测定葡萄糖酸钙注射液中的有关物质,可为本品的工艺优化和质量控制提供参考依据。OBJECTIVE To develop a method for related substances of Calcium Gluconate injection,and to identify the structure of impurity whose relative retention time(RRT) was 4.18.METHODS The related substances were determined by HPLC,which was performed on Xbridge C8 column(250 mm×4.6mm,5 μm),the moblie phase was 0.1 mol·L^(-1) dipotassium phosphate and 1 mmol·L^(-1) tetrabutylammonium hydroxide(pH adjusted to 5.5 by phosphoric acid),the detection wavelength was 210 nm.HPLC-Q-TOF/MS was used to identify the structure of impurity(RRT 4.18).RESULTS The separation of gluconic acid and its related substances was good.Impurity RRT 4.18 was supposed to be 5-hydroxymethyl furoic acid.The calibration curves of 5-hydroxymethyl furoic acid was linear in range of 0.18-2.26 μg·m L^(-1)(r=0.999 0),and its detection limit was 0.06 μg·m L^(-1).CONCLUSION The HPLC method established is accutrate to determine the related substances in Calcium Gluconate injection,which can provide references for the process optimization and quality control of Calcium Gluconate injection.

关 键 词：葡萄糖酸钙注射液 有关物质 高效液相色谱法 结构鉴定 

分 类 号：R917[医药卫生—药物分析学]