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.