Simultaneous quantification of evodiamine,rutaecarpine,and dehydroevodiamine in rat cerebrospinal fluid and cerebral nuclei after oral administration by UPLC-MS/MS  

液质联用法测定吴茱萸碱、吴茱萸次碱、去氢吴茱萸碱在大鼠脑脊液和脑组织中的分布

作　　者：Yanfang Yang Yinan Zhang Youbo Zhang Xiuwei Yang 杨雁芳;张伊楠;张友波;杨秀伟(北京大学医学部北京大学药学院天然药物及仿生药物国家重点实验室天然药物学系,北京100191)

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Department of Natural Medicines,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2022年第1期13-22,共10页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81773865);the National Key R&D Program of China(Grant No.2018YFC1704500,2018YFC1704506)。

摘　　要：Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.吴茱萸碱、吴茱萸次碱、去氢吴茱萸碱是吴茱萸中主要的生物碱类成分。为研究吴茱萸主要生物碱成分在大鼠脑脊液中的代谢和在脑组织中的分布,吴茱萸碱、吴茱萸次碱、去氢吴茱萸碱以1:1:1的质量比混合,以15 mg/kg的剂量灌胃给予大鼠。本文建立了同时测定大鼠脑脊液和脑组织中三个生物碱成分的液质联用方法,测定结果显示,三个生物碱成分能快速吸收进入脑脊液并分布到脑组织,并能快速消除。三个成分在脑组织中的分布特点不同,吴茱萸碱在小脑和脑干分布最多,而吴茱萸次碱和去氢吴茱萸碱分别在脑干、小脑和海马分布最多。本研究结果揭示了吴茱萸碱、吴茱萸次碱和去氢吴茱萸碱在脑内分布的差异,为进一步研究中药吴茱萸果实治疗脑病的药效物质基础提供了依据。

关 键 词：EVODIAMINE RUTAECARPINE Dehydroevodiamine Cerebrospinal fluid Cerebral nuclei UPLC-MS/MS 

分 类 号：R917[医药卫生—药物分析学]