UPLC-MS/MS测定大鼠血浆中胡蔓藤碱乙和胡蔓藤碱丁及其药动学与生物利用度研究

目的 建立一种检测大鼠血浆中蔓藤碱乙和胡蔓藤碱丁的UPLC-MS/MS法，并研究大鼠口服和舌下静脉给药方式下胡蔓藤碱乙和胡蔓藤碱丁的药动学差异。方法 大鼠分别灌胃和舌下静脉注射蔓藤碱乙和胡蔓藤碱丁，在一定时间内取血，离心获得血清；士的宁为内标，通过UPLC-MS/MS来测定血清中蔓藤碱乙和胡蔓藤碱丁的浓度，绘制药-时曲线，计算药动学参数。结果 经灌胃给药5 mg·kg^–1，胡蔓藤碱乙的t_1/2为(5.7±1.2) h，AUC_(0-t)为(59.6±20.1) ng·h·mL^–1，CL/F为(89.1±30.5) L·h^–1·kg^–1，C_max为(18.3±5.3) ng·mL^–1；经舌下静脉给药1 mg·kg^–1后，胡蔓藤碱乙的t_1/2为(1.5±0.3) h，AUC_(0-t)为(140.2±37.4) ng·h·mL^–1，CL为(7.6±2.3) L·h^–1·kg^–1，C_max为(114.9±36.0) ng·mL^–1。经灌胃给药5 mg·kg^–1，胡蔓藤碱丁的t_1/2为(4.7±4.1) h，AUC_(0-t)为(44.3±5.1) ng·h·mL^–1，CL/F为(100.3±11.7) L·h^–1·kg^–1，C_max为(13.0±4.0) ng·mL^–1；经舌下静脉给药0.1 mg·kg^–1后，胡蔓藤碱丁的t_1/2为(1.1±0.4) h，AUC_(0-t)为(72.9±19.1) ng·h·mL^–1，CL为(1.4±0.4) L·h^-1·kg^–1，C_max为(43.7±6.8) ng·mL^–1。胡蔓藤碱乙的生物利用度为8.5%；胡蔓藤碱丁的生物利用度为1.2%。结论 胡蔓藤碱乙、胡蔓藤碱丁吸收迅速，半衰期较短。

Determination of Humantenine and Humantenirine in Rat Plasma by UPLC-MS/MS and Their Pharmacokinetics and Bioavailability

OBJECTIVE To establish an UPLC-MS/MS method for the detection of humantenine and humantenirine in rat plasma,and to study the pharmacokinetics of humantenine and humantenirine under oral and sublingual vein administration in rats.METHODS Rats were given intragastric and sublingual intravenous injections of humantenine and humantenirine.The blood was collected within a certain period of time,and the plasma was obtained by centrifugation;strychnine was used as an internal standard,the concentrations of humantenine and humantenirine in plasma was determined by UPLC-MS/MS,the concentration-time curve was drawn,and the pharmacokinetic parameters were calculated.RESULTS After intragastric administration of 5 mg·kg^–1,the t_1/2 of humantenine was (5.7±1.2) h,AUC_(0-t) was (59.6±20.1) ng·h·mL^–1,and CL/F was (89.1±30.5) L·h^–1·kg^–1,C_max was (18.3±5.3) ng·mL^–1;after sublingual intravenous administration of 1 mg·kg^–1,the t_1/2 of humantenine was (1.5±0.3) h,and the AUC_(0-t) was (140.2±37.4) ng·h·mL^–1,CL was (7.6±2.3) L·h^–1·kg^–1,C_max was (114.9±36.0) ng·mL^–1.After intragastric administration of 5 mg·kg^–1,the t_1/2 of humantenirine was (4.7±4.1) h,the AUC_(0-t) was (44.3±5.1) ng·h·mL^–1,and the CL/F was (100.3±11.7) L·h^–1·kg^–1,C_max was (13.0±4.0) ng·mL^–1;after sublingual intravenous administration of 0.1 mg·kg^–1,the t_1/2 of humantenirine was (1.1±0.4) h,and the AUC_(0-t) was (72.9±19.1) ng·h·mL^–1,CL was (1.4±0.4) L·h^–1·kg^–1,C_max was (43.7±6.8) ng·mL^–1.The bioavailability of humantenine was 8.5%;the bioavailability of humantenirine was 1.2%.CONCLUSION The absorption of humantenine and humantenirine is rapid and has a short half-life.