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

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T_max为1 h，最大血药浓度C_max为614.92 μg·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(MetabolitePilot^TM). 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 T_max was 1 h,the C_max was 614.92 μg·L^-1,and the t_1/2 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.