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：郭延垒[1] 王勇德 师萱[1] 刘晓玲[1] 谭春斌[1] 杨大坚[1] 阳勇[1] GUO Yan-lei, WANG Yong-de, SHI Xuan, LIU Xiao-ling, TAN Chun-bin, YANG Da-jian, YANG Yong(Chongqing Academy of Chinese Material Medical, Chongqing 400065, China)

机构地区：[1]重庆市中药研究院,重庆400065

出　　处：《药物分析杂志》2018年第3期418-424,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：重庆市科委应用开发(重大)项目(cstc2014yykf C10004);重庆市科委社会事业与民生保障科技创新专项(cstc2017shms A130090;cstc2017 shms A130035)

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2 955.30μg·L^(-1)·h^(-1),平均驻留时间MRT_((0-t))为3.78 h,达峰时间T_(max)为1 h,最大血药浓度C_(max)为614.92μg·L^(-1),末端消除半衰期t_(1/2)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。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.

关 键 词：甲基斑蝥胺 体内过程 代谢产物 斑蝥胺 氧化斑蝥胺 去甲基氧化斑蝥胺 双去甲基氧化斑蝥胺 去三甲基氧化斑蝥胺 液相色谱质谱 多重质量亏损 

分 类 号：R917[医药卫生—药物分析学]