摘要
目的:采用色谱-质谱联用技术对注射用棓丙酯、棓丙酯注射液和棓丙酯氯化钠注射液中有关物质进行结构解析。方法:采用C_(18)色谱柱(2.1 mm×50 mm,1.7μm),以乙腈-0.05%甲酸(20∶80)为流动相,流速为0.2 mL·min^(-1),检测波长为272 nm,对注射用棓丙酯(来自13家企业)、棓丙酯注射液(来自6家企业)和棓丙酯氯化钠注射液(来自3家企业)中有关物质进行分离;采用电喷雾负离子化的方法,通过飞行时间质谱(TOF-MS)测定一级质谱精确质量,三重四极杆质谱扫描二级质谱(MS/MS),并进行结构解析。结果:棓丙酯与杂质分离良好,6家企业的注射用棓丙酯中检出同1个杂质,命名为杂质Ⅰ,1家企业的棓丙酯氯化钠注射液检出另1个杂质,命名为杂质Ⅱ。采用液相色谱-质谱联用法对杂质Ⅰ和杂质Ⅱ进行了结构解析,推测杂质Ⅰ为棓丙酯二聚物,为粉针剂生产过程中长时间加热产生,推测杂质Ⅱ为棓丙酯与辅料亚硫酸氢钠发生磺酸化反应的产物,为棓丙酯氯化钠注射液贮藏过程中产生。结论:色谱-质谱联用技术能有效地对3种剂型棓丙酯注射剂中的有关物质进行结构解析,为其工艺和质量控制提供参考依据。
Objective： To identify the related substances in propylgallate for injection,propylgallate injection and propylgallate and sodium chloride injection by LC-MS method.Methods： The analysis was performed on a C18（2.1 mm×50 mm,1.7 μm）column and the mobile phase was acetonitrile-0.05% formic acid aqueous solution（20：80）at a flow rate of 0.2 mL·min-1.The detection wavelength was 272 nm.Electrospray ionization source was operated in negative ion mode.The structures of the related substances in propylgallate for injection from thirteen producers,propylgallate injection from six producers and propylgallate and sodium chloride injection from three producers were speculated by TOF-MS for accurate ion mass determination and by LC-MS/MS for product ion scanning.Results： Propylgallate and the related substances were well separated.An impurity which was named related substance Ⅰ was found in the propylgallate for injection from six producers.Another impurity which was named related substance Ⅱ was found in the propylgallate and sodium chloride injection from one producer.The related substances Ⅰ and Ⅱ were identified by LC-MS techniques.The speculative results were as follows：The related substance Ⅰ was the dipolymer of the propylgallate and produced by heating process of propylgallate for injection for a long time.The related substance Ⅱ was the reaction product from the propylgallate and the sodium hydrogen sulfite and produced during the storage process of the propylgallate and sodium chloride injection.Conclusion： The LC-MS method is useful for the identification of related substances in propylgallate for injection,propylgallate injection and propylgallate and sodium chloride injection.The results obtained are valuable for its manufacturing process and quality control.
作者
刘荷英
程奇珍
钟振华
夏红英
LIU He-ying1,2, CHEN Qi-zhen1, 2, ZHONG Zhen-hua1,2, XIA Hong-ying1,2(1. Jiangxi Institute for Drug Control, Nanchang 330029, China; 2. Jiangxi Provincial Engineering Research Center for Drug and Medical Device Quality, Nanchang 330029, China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2018年第3期455-463,共9页
Chinese Journal of Pharmaceutical Analysis
关键词
棓丙酯
杂质
棓丙酯二聚物
棓丙酯磺酸化产物
结构解析
质谱裂解
飞行时间质谱
液相色谱质谱联用
propylgallate
related substances
dipolymer of propylgallate
reaction produet from propylgallate and soldium hydrogen sulfite
structure identification
MS fragmentation
TOF-MS
LC-MS/MS
