新型Gi蛋白偏向性阿片受体(MOR)激动剂LPM3480392原料药有关物质测定  

Determination of Related Substances in the Novel Gi Protein-biased Opioid Receptor(MOR) Agonist LPM3480392 Active Pharmaceutical Ingredients

作　　者：冯聪睿 王丹 李丽霞 王淑萍 张连庆 徐志红 周凤梅 车鑫[1,3] FENG Congrui;WANG Dan;LI Lixia;WANG Shuping;ZHANG Lianqing;XU Zhihong;ZHOU Fengmei;CHE Xin(Key Laboratory of Molecular Pharmacology and Drug Evaluation,Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,School of Pharmacy,Yantai University,Yantai 264005,China;Shenyang Institute for Food and Drug Control,Shenyang 110000,China;State Key Laboratory of Long-acting and Targeting Drug Delivery System,Shandong Luye Pharmaceutical Co.,Ltd.,Yantai 264003,China)

机构地区：[1]烟台大学药学院分子药理和药物评价教育部重点实验室,新型制剂与生物技术药物研究山东省高校协同创新中心,山东烟台264005 [2]沈阳市食品药品检验所,沈阳110000 [3]绿叶制药有限公司长效和靶向制剂国家重点实验室,山东烟台264003

出　　处：《中国现代应用药学》2024年第3期372-377,共6页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的建立新型Gi蛋白偏向性阿片受体(MOR)激动剂LPM3480392的有关物质测定方法。方法采用Waters Symmetry Shield RP18(150 mm×4.6 mm,3.5μm)色谱柱,以0.0025 mol·L^(-1)辛烷磺酸钠的0.01 mol·L^(-1)磷酸二氢钾水溶液(含0.1%的三乙胺,磷酸调节pH 2.50)和乙腈为流动相,梯度洗脱,流速1.0 mL·min^(-1),紫外检测波长210 nm。结果LPM-3480392与杂质A、杂质B、杂质C、杂质E、杂质F的色谱峰能够完全分离。LPM3480392质量浓度在0.0649~5.1912μg·mL^(-1)内线性关系良好;杂质A、B、C、E、F质量浓度分别在0.0666~7.6104μg·mL^(-1),0.1660~3.7940μg·mL^(-1),0.2092~4.4632μg·mL^(-1),0.1679~7.6726μg·mL^(-1),0.0164~7.5057μg·mL^(-1)线性关系良好;回收率在93.0%~103.2%。结论该方法可准确测定LPM3480392的有关物质,可为LPM3480392的后续研究与开发提供有价值的参考。OBJECTIVE To establish a determination method for the related substances of LPM3480392,a novel Gi protein-biased opioid receptor(MOR)agonist.METHODS The separation was carried out with Waters Symmetry Shield RP18(150 mm×4.6 mm,3.5μm)by gradient elution method,using a mixture of 0.0025 mol·L^(-1) sodium 1-octanesulfonate monohydrate in 0.01 mol·L^(-1) potassium dihydrogen phosphate-water solution(containing 0.1%triethylamine,adjusted pH to 2.50 with phosphate acid)and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min^(-1) and the UV detection wavelength was set at 210 nm.RESULTS The chromatographic peaks of LPM3480392 and impurity A,impurity B,impurity C,impurity E and impurity F could be completely separated,the linear relationship of LPM3480392 was good in 0.0649-5.1912μg·mL^(-1),while impurity A,impurity B,impurity C,impurity E and impurity F showed good linear relationship within 0.0666-7.6104μg·mL^(-1),0.1660-3.7940μg·mL^(-1),0.2092-4.4632μg·mL^(-1),0.1679-7.6726μg·mL^(-1) and 0.0164-7.5057μg·mL^(-1),respectively.The recovery rate was within 93.0%-103.2%.CONCLUSION The method is suitable for the determination of related substances in LPM3480392,and can provide valuable reference for the follow-up research and development of LPM3480392.

关 键 词：镇痛药物 Gi蛋白偏向性阿片受体激动剂 LPM3480392 有关物质 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]