摘要
目的:分析双环醇、联苯双酯和五味子丙素的质谱裂解规律,鉴定双环醇原料药中的杂质。方法:采用超高效液相色谱-电喷雾-四极杆-飞行时间质谱法,以电喷雾电离源为离子源,在正离子模式下,利用飞行时间质谱对双环醇、联苯双酯和五味子丙素的准分子离子及其特征碎片离子信息进行分析,根据碎片质量变化推测可能的裂解途径,分析总结其质谱裂解规律;双环醇原料药样品首先通过液相色谱分离,寻找其中的杂质峰,然后利用质谱对杂质峰进行分析,结合裂解规律辅助鉴定杂质的结构。结果:3种化合物在正离子模式下均产生[M+H]+的准分子离子,经碰撞诱导解离后发生C—O键、C—C键的简单断裂以及氧环的开环断裂,并伴随以CH2O为主,CO2、CO、CHO为辅的中性碎片丢失,解离均集中在中高质量区。3种化合物只有支链结构和/或氧环结构发生C—C、C—O键的简单断裂,而联苯母核结构未曾改变。其中,双环醇由于含有苄位羟基结构,故在酸性流动相条件下,会以[M+H-H2O]+的形式稳定存在;五味子丙素因其含有八元环结构,故碰撞电压下率先出现开环,继而再出现中性碎片丢失。双环醇原料药中杂质的二级质谱与联苯双酯的二级碎片表现出的质谱裂解行为基本一致。结论:本研究归纳了3种五味子衍生物的质谱裂解规律。双环醇原料药中出现的杂质可能为联苯双酯。
OBJECTIVE:To analyze the mass spectrometry fragmentation regularity of bicyclol,bifendate and schisandrin C,and to identify the impurities of bicyclol raw material.METHODS:UHPLC-ESI-Q-TOF-MS method was adopted.Using electrospray ionization source,in positive ion mode,the excimer ion and characteristic fragments of bicyclol,bifendate and schisandrin C were analyzed by means of TOF-MS.According to the mass change of fragments,the possible fragmentation pathways were speculated,and the fragmentation regularity were analyzed and summarized.Bicyclol raw material sample was first separated by liquid chromatography to find the impurity peaks in it,and then the impurity peaks were analyzed by mass spectrometer;the impurity identification was conducted by combining with the fragmentation regularity.RESULTS:The 3 compounds all produced[M+H]+excimer ion in the positive ion mode.After collision-induced dissociation,the C-O bond,the simple rupture of the C-C bond and the ring-opening cleavage of the oxygen ring occurred;with the loss of neutral fragments,mainly CH2O,supplemented by CO2,CO and CHO,the dissociation was concentrated in the middle and high quality regions.C-C and C-O bonds of 3 compounds were simply broken only in the branched chain structure and/or oxygen ring structure,but the structure of the biphenyl parent nucleus remained unchanged.Among them,the bicyclol contained a benzyl alcohol structure,so under acidic mobile phase conditions,it would exist stably in the form of[M+H-H2O]+.Because schisandrin C contained 8-membered ring structure,ring opening first occurred under collision voltage,and then neutral fragment loss occurred.The secondary mass spectra of impurity in bicyclol raw material were consistent with the mass spectra fragmentation of secondary fragments of bifendate.CONCLUSIONS:The study summarized mass spectrometry fragmentation regularity of 3 schisandrin derivatives.The impurity in bicyclol raw material may be bifendate.
作者
段华健
武正华
余史丹
汪硕闻
陈明
范国荣
DUAN Huajian;WU Zhenghua;YU Shidan;WANG Shuowen;CHEN Ming;FAN Guorong(School of Pharmacy,Shanghai Jiaotong University,Shanghai 201100,China;Dept.of Clinical Pharmacy,the First Affiliated People’s Hospital of Shanghai Jiaotong University,Shanghai 200080,China;Dept.of Pharmacy,No.906 Hospital of the Joint Logistics Support Force of PLA,Zhejiang Ningbo 315040,China)
出处
《中国药房》
CAS
北大核心
2021年第14期1692-1697,共6页
China Pharmacy
基金
国家自然科学基金资助项目(No.81973289)
上海市科学技术委员会科研计划项目(课题)(No.18401931900)
上海市临床重点专科项目(No.shslczdzk01903)。
