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一种灵敏的超快速液相色谱-串联质谱法,用于同时测定大鼠血浆中灯盏细辛注射液的十种成分,并将其应用于假手术和大脑中动脉闭塞大鼠的比较药代动力学研究。

A sensitive ultra-fast liquid chromatography with tandem mass spectrometry method for simultaneous determination of ten constituents of Deng-Zhan-Xi-Xin injection in rat plasma and its application to a comparative pharmacokinetic study in sham and middle cerebral artery occlusion rats.

机构信息

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, P. R. China.

出版信息

J Sep Sci. 2020 Nov;43(22):4162-4177. doi: 10.1002/jssc.202000661. Epub 2020 Sep 30.

Abstract

Deng-Zhan-Xi-Xin injection is widely used to treat cerebrovascular and cardiovascular diseases in clinical practice. A rapid and selective method based on ultra-fast liquid chromatography with tandem mass spectrometry was established and validated to simultaneously quantify chlorogenic acid, 1,3-O-dicaffeoylquinic acid, isochlorogenic acid A, neochlorogenic acid, erigeside I, cryptochlorogenic acid, apigenin-7-O-glucuronide, scutellarin, isochlorogenic acid B, and isochlorogenic acid C of Deng-Zhan-Xi-Xin injection in both sham and middle cerebral artery occlusion rats. This was the first quantitative analysis of these ten constituents in both sham and middle cerebral artery occlusion rats. Chromatographic separation of these ten constituents was accomplished on an Acquity HSS T3 column with the mobile phase consisting of acetonitrile and 0.1% formic acid in water. Mass analysis was performed in negative ion mode with an electrospray ionization source using multiple reaction monitoring technology. The pharmacokinetic study of the ten constituents in sham and middle cerebral artery occlusion rats after intravenous administration of Deng-Zhan-Xi-Xin injection was successfully accomplished by using this validated method. Based on the results of pharmacokinetic parameters, significant differences were observed between the two groups, which might be due to the pathological factors of middle cerebral artery occlusion and pharmacological effects of Deng-Zhan-Xi-Xin injection.

摘要

灯盏细辛注射液在临床上广泛用于治疗脑血管和心血管疾病。建立并验证了一种基于超快速液相色谱-串联质谱的快速、选择性方法,用于同时定量测定灯盏细辛注射液中绿原酸、1,3-O-二咖啡酰奎宁酸、异绿原酸 A、新绿原酸、淫羊藿苷 I、隐绿原酸、芹黄素-7-O-葡萄糖醛酸、野黄芩苷、异绿原酸 B 和异绿原酸 C。这是首次对假手术和大脑中动脉闭塞大鼠中这十种成分进行定量分析。这些十种成分的色谱分离在 Acquity HSS T3 柱上完成,流动相由乙腈和水中的 0.1%甲酸组成。质谱分析采用电喷雾电离源在负离子模式下,采用多反应监测技术进行。采用验证后的方法成功完成了灯盏细辛注射液静脉给药后假手术和大脑中动脉闭塞大鼠中十种成分的药代动力学研究。基于药代动力学参数的结果,两组之间观察到显著差异,这可能是由于大脑中动脉闭塞的病理因素和灯盏细辛注射液的药理作用所致。

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