LC-MS/MS法分析去水山莨菪碱在大鼠体内的药代动力学研究  

Study on pharmacokinetics of raceanisodamine impurityⅠin Rats by LC-MS

作　　者：吴瑞 刘艳芳 张芳[1] 姚辰昊 余宇洁 张建兰 代书 万峰[1,2] 南峰 李芸霞 WU Rui;LIU Yan-fang;ZHANGFang;YAO Chen-hao;YU Yujie;ZHANG Jian-lan;DAI Shu;WAN Feng;NAN Feng;LI Yun-xia(School of Pharmacy,State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan;Chengdu NO.1 Pharmaceutical Co.,Ltd.,Pengzhou 610031,Sichuan;Drug Clinical Trial Institution,The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,Sichuan)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,四川成都611137 [2]成都第一制药有限公司,四川成都610031 [3]成都中医药大学附属医院国家药物临床试验机构,四川成都610075

出　　处：《中药与临床》2023年第6期65-68,共4页Pharmacy and Clinics of Chinese Materia Medica

基　　金：四川省科技厅应用基础项目(2021JDKY0013)。

摘　　要：目的:评价不同给药途径和剂量对氢溴酸山莨菪碱(Ani HBr)代谢物去水山莨菪碱(RIMP I)在大鼠体内的药代动力学特征的影响。方法:使用LC-MS/MS技术建立RIMP I在大鼠血浆中的生物分析方法。大鼠灌胃氢Ani HBr片(12.5、25、50 mg·kg^(-1))以及尾静脉注射Ani HBr注射液(4、8、16 mg·kg^(-1))后,于不同时间点采集血浆以检测RIMP I的血药浓度,评估RIMP I在大鼠体内的药代动力学参数。结果:测定大鼠血浆中RIMP I的方法专属性良好,线性范围为1~500 ng·mL^(-1),批内及批间精密度(RSD)均<11.0%,准确度为91.1~107.5%,基质效应无明显干扰,达到生物样本分析方法要求。通过灌胃和尾静脉注射给药,在不同剂量下发现RIMP I的药代动力学特征可能呈非线性动力学过程。结论:基于LC-MS/MS技术,建立了RIMP I在大鼠血浆中的方法学并评价了其药代动力学特征。Objective:To evaluate the influence of different administration routes and doses on the pharmacokinetic characteristics of dehydrated anisodamine(RIMP I)in rats.Method:High performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was used to establish a bioanalysis method for RIMP I in rat plasma.After intragastric administration of anisodamine hydrobromide(Ani HBr)tablets(12.5,25,50 mg·kg&(-1))and tail vein injection of Ani HBr injection(4,8,16 mg·kg&(-1))in rats,plasma was collected at different time points to detect the plasma concentration of RIMP I and evaluate its pharmacokinetic parameters in rats.Result:The method for determining RIMP I in rat plasma had good speciffcity,with a linear range of 1~500 ng·mL&(-1).The intra and inter batch precision(RSD)were lower than 11.0%,and the accuracy was at 91.1~107.5%.The matrix effect had no signiffcant interference,meeting the requirements of biological sample analysis methods.Through oral and intravenous administration,it was found that the pharmacokinetic characteristics of RIMP I may exhibit a nonlinear kinetic process at different doses.Conclusion:With the support of LC-MS/MS technology,a methodology for RIMP I in rat plasma is established and its pharmacokinetic characteristics are evaluated.

关 键 词：LC-MS/MS 去水山莨菪碱 药代动力学 

分 类 号：R285.5[医药卫生—中药学]