摘要
采用质谱技术,利用手性探针酰氯对盐酸兰地洛尔及其3个立体异构体进行了区分识别研究。本研究采用了两个手性酰氯探针N-对甲苯磺酰基-L-苯丙氨酰氯(TSPC)和(-)-莰烷酰氯与盐酸兰地洛尔反应产生共价结合产物,放大了盐酸兰地洛尔与其立体异构体的结构差异。在二级串联质谱实验中,与手性酰氯探针结合的产物容易丢失羟基产生碎片离子m/z 793和672,在不同构型的产物离子所产生的丢失水分子的碎片离子的丰度具有一定差异,(-)-莰烷酰氯衍生化产物的碎片离子m/z 603由于立体结构差异,导致稳定性不同,使得不同构型的碎片离子丰度产生差异,可通过比较药物和异构体杂质在二级质谱中特征碎片离子丰度的差异,实现盐酸兰地洛尔及其立体异构体的有效区分识别。所有碎片的元素组成都经过高分辨质谱进行确证。本研究通过质谱法对于盐酸兰地洛尔及其立体异构体进行快速、简单的区分识别,为盐酸兰地洛尔立体异构体杂质的质谱分析相关研究提供数据支持。
In this work,two chiral chloride probes were used to differentiate landiolol hydrochloride by mass spectrometry.Two chiral chloride probe reagents,N-(p-Tosyl)-L-phenylalaninyl chloride(TSPC)and(-)-Camphanic acid chloride,were chosen to react with landiolol hydrochloride and its stereoisomers to form covalent bonding derivatives,which enlarged the difference of stereo structure between landiolol and its stereoisomers.Result of tandem mass spectrometry showed that fragment from derivative products prefers to losing water to form fragment ions m/z 793 and m/z 672.The relative abundance of ions m/z 793 and m/z 672 was quite different in each isomer.The fragment ions m/z 603 from(-)-Camphanic acid chloride derivative products showed distinction relative abundance because of the different stability of each stereoisomers,which gave rise to the enlarged difference of stereo structure between landiolol and its stereoisomers.By comparing the different relative abundance ratio of analyte and each stereoisomer in MS/MS spectra,we could realize recognization landiolol hydrochloride and its stereoisomers.Accurate masses of precursor and fragment ions were confirmed on an IT-TOF mass spectrometer.This method by using ion-trap mass spectrometry could rapidly and simply differentiate landiolol hydrochloride and its stereoisomers.This work could also contribute to differentiation and discrimination of landiolol hydrochloride and its stereoisomers.
作者
戴田行
张才煜
耿颖
何兰
DAI Tian-Xing;ZHANG Cai-Yu;GENG Ying;HE Lan(National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《分析化学》
SCIE
EI
CAS
CSCD
北大核心
2018年第3期332-341,共10页
Chinese Journal of Analytical Chemistry
基金
科技重大专项重大新药创制项目(No.2015ZX09303001)资助~~
关键词
手性探针
识别
质谱
盐酸兰地洛尔
Chiral probe
Recongnition
Mass spectrometry
Landiolol hydrochloride
