新型睡眠促进剂褪黑激素(Melatonin)的药代动力学研究

摘要

The plasma concentration of melatonin in rabbits are measured by GC/MS with selected ion (m/z 173) and caffeine(m/z 194) as internal standard to determine the pharmacokinetic of melatonin. The concentrtion-time profile of melatonin is abtained after melatonin 30 mg*kg-1 administered for a two-compartment open model in rabbits. The pharmacokinetic parameters are t1/2α=0.31 h, t1/2β=8.58 h, t1/2Ka=0.34 h, Tmax=0.63±0.47 h, Cmax=322.23±255.40 ng/mL, K12=0.81 h-1, K21=2.80 h-1, K10=2.10 h-1, AUC=697.49(ng/mL)*h,CL(s)=0.097±0.054(mg/kg)/h(ng/mL). The method is stable, sensitive and accurate. It is a useful method for the determination of pharmacokinetics of melatonin which is important for clinic.%测定新型睡眠促进剂Melatonin的药代动力学参数的方法是以咖啡因为内标、以GC/MS的SIM(选择性离子监测)为检测手段,定量测定家兔体内Melatonin的含量及药代动力学参数.其结果为家兔灌胃给予Melatonin 30 mg*kg-1后,Melatonin在家兔体内呈二室分布,药代动力学参数为t1/2α=0.31 h,t1/2β=8.58 h,t1/2Ka=0.34 h,Tmax=0.63±0.47 h,Cmax=322.23±255.40 ng/mL, K12=0.81 h-1,K21=2.80 h-1,K10=2.10 h-1,AUC=697.49(ng/mL)*h,CL(s)=0.097±0.054(mg/kg)/h/(ng/mL).这种测量方法灵敏度高、特异性强、准确性好,为测定Melatonin药代动力学参数提供了有效实用的分析方法.Melatonin在家兔体内分布及消除都很快,不会在体内蓄积.