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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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基于高分辨质谱技术的甲基斑蝥胺在小鼠体内的代谢分析

Analysis of N-methylcantharidimide metabolites in mice based on high resolution mass spectrometry

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (3):418-424
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:采用高分辨质谱技术对甲基斑蝥胺在小鼠体内的代谢物进行系统分析。方法:以甲基斑蝥胺为研究对象,借助UPLC/Q-TOF高分辨质谱系统,基于多重质量亏损技术,应用代谢物分析鉴定软件,系统分析甲基斑蝥胺在小鼠体内的代谢过程及产物,并对甲基斑蝥胺在小鼠体内药代动力学进行研究。结果:甲基斑蝥胺在小鼠体内经I相代谢后,生成甲基斑蝥胺去甲基、氧化、去甲基后氧化、双去甲基后氧化、去三甲基、去三甲基后氧化等在内的7种代谢产物,甲基斑蝥胺在小鼠体内主要药代动力学参数中,药时曲线下面积AUC(0-t)为2 955.30 μg·L-1·h-1,平均驻留时间MRT(0-t)为3.78 h,达峰时间Tmax为1 h,最大血药浓度Cmax为614.92 μg·L-1,末端消除半衰期t1/2为0.92 h。结论:本实验鉴定分析了甲基斑蝥胺在小鼠体内的代谢过程,并对其体内药代动力学进行研究,为甲基斑蝥胺在新药发现方面研究提供重要参考。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To investigate the metabolites rule of the N-methylcantharidimide in mice by high resolution mass spectrometry(HRMS). Methods: An efficient strategy was developed for the identification of the metabolites of N-Methylcantharidimide using ultra high performance liquid chromatography equipped with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF)method combined with multiple mass defect filter(MMDF)and a data mining software(MetabolitePilotTM). The pharmacokinetic of N-methylcantharidimide was studied in vivo of mice. Results: Based on the metabolism of phaseⅠ,multiple metabolites of N-methylcantharidimide including loss of CH2 and/or oxidation were found in mice after the oral administration of N-methylcantharidimide tablets. The pharmacokinetic of AUC(0-t) of N-methylcantharidimide was 2 955.30 μg·L-1·h-1,the MRT(0-t) was 3.78 h,the Tmax was 1 h,the Cmax was 614.92 μg·L-1,and the t1/2 was 0.92 h. Conclusion: This study provided a practical strategy for rapidly identifying metabolites and the pharmacokinetic of N-methylcantharidimide in vivo of mice. The results can provide a key reference for the clinical use of N-methylcantharidimide.

-----参考文献:---------------------------------------------------------------------------------------
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