琥珀酸普芦卡必利的降解试验及降解产物的结构鉴定  

Degradation test and structure identification of Prucalopride succinate

作　　者：闫翔宇 梅雪娇 严相平 YAN Xiangyu;MEI Xuejiao;YAN Xiangping(Pharmaceutical Department,Jiangsu Provincial Institute of Materia Media,Nanjing,Jiangsu,210009 P.R.China;Nanjing Polytechnic Institute,Nanjing,Jiangsu,210044 P.R.China)

机构地区：[1]江苏省药物研究所有限公司药学部,江苏南京210009 [2]南京科技职业学院,江苏南京210044

出　　处：《华西药学杂志》2023年第5期530-533,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的 研究琥珀酸普芦卡必利在酸、碱、氧化、光照等条件下强制破坏产生的降解杂质结构和来源。方法 在各条件下强制破坏琥珀酸普芦卡必利,得到降解产物;采用Kromasil C18色谱柱(150 mm×3 mm, 5μm),以磷酸盐缓冲液-乙腈-甲醇(90:5:5)为流动相A,甲醇-乙腈(1:1)为流动相B,梯度洗脱,分离得到有关物质。利用MS研究主要降解杂质的结构,归属杂质来源,推测形成路径。结果 推测降解产物为4-氨基-5-氯-N-[1-(3-甲氧基丙基)-4-哌啶基]-7-苯并呋喃甲酰胺、4-氨基-5-氯-2,3-二氢-N-[1-氧-1-(3-甲氧基丙基)-4-哌啶基]-7-苯并呋喃甲酰胺、2-羟基-4-氨基-5-氯-2,3-二氢-N-[1-(3-甲氧基丙基)-4-哌啶基]-7-苯并呋喃甲酰胺、4-氨基-2,3-二氢-N-[1-(3-甲氧基丙基)-4-哌啶基]-7-苯并呋喃甲酰胺。结论 成功推测了琥珀酸普芦卡必利强制碱、氧化、光降解产物的结构,并阐明其产生途径,可为琥珀酸普芦卡必利的稳定性研究及质量控制提供依据。OBJECTIVE To study the structure and source of degradation impurities produced by forced destruction of Prucalopride succinate(PS)under conditions such as acid,alkali,oxidation,and light.METHODS Under various conditions,PS was forcibly destroyed to obtain degradation products.Separation was performed using Kromasil C18 column(150 mm×3 mm,5μm),with phosphate buffer-acetonitrile-methanol(90∶5∶5)as mobile phase A and methanol-acetonitrile(1∶1)as mobile phase B.Then gradient elution was conducted to obtain relevant substances.To study the structure of major degradation impurities,MS was used to identify their sources,and speculate on their formation pathways.RESULTS Degradation products mainly include 4-amino-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide,4-amino-5-chloro-2,3-dihydro-N-[1-oxo-1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide,2-hydroxy-4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide,and 4-amino-5-chloro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide.CONCLUSION The structures of the degradation products were successfully speculated following forced alkali,oxidation,and photodegradation of PS.Also,elucidating its production pathway can provide a basis for the stability research and quality control of PS.

关 键 词：琥珀酸普芦卡必利 强制降解试验 梯度洗脱 降解杂质 结构推测 杂质收集 质谱 结构确证 降解途径 

分 类 号：R917[医药卫生—药物分析学]