乌头类有毒中药生物碱体内吸收 分布 排泄的分析-analysis of absorption, distribution and excretion of aconitum alkaloids.docx

子离子[M+H]+存在离子流峰。结论：大鼠口服附子总生物碱后，发现三种生物碱吸收快，并在短时间内血药浓度快速下降，提示吸收后分布快，在30-360分钟内血药浓度保持相对平稳，同时具有多峰现象。脏器分布研究表明，乌头碱、新乌头碱和次乌头碱在大鼠体内组织脏器的分布较为广泛，肝脏、肺脏中的含量较高。排泄研究提示尿液是乌头碱、新乌头碱及次乌头碱原型药的重要排除途径，其中乌头碱、新乌头碱的24h平均排除率均为30％左右，次乌头碱的24h平均排除率相对较低，仅为乌头碱、新乌头碱的一半即15.36±1.29％，提示次乌头碱在体内相对较难于排出。在各胆汁样品中均未检测出乌头碱、新乌头碱及次乌头碱。提示乌头碱、新乌头碱及次乌头碱原药排泄的主要途径可能不是胆汁。StudyontheAbsorption,DistributionandEliminationofAconitumAlkaloids（Abstract）ChengDuUniversityofTCMGrade2005Master:TaoChang-geFacultyAdviserProfPengChengObject:Tostudytheabsorption(A)，distribution(D),andelimination(E)afteriv.aconitine,mesaconitineandhypaconitine,respectively,andpo.Aconitumalkaloid;discussthetoxicmechanismoftheherbsofgenusAconituminfamilyofRanunculaceae.MethodsandResults1MethodsWesuccessfullyestablishedthemethodofHPLC-MS-MStodetectaconitinemesaconitineandhypaconitineinbiologicalsamplesincludingplasma,bile,urineandorgans.Themethod(HPLC-MS-MS)issimpleandefficientwithexcellentaccuracy,precision,reproducibilityandlowdetectionlimit.Itcanofferbiologicalanalysisinallcalibrationcurves.Wecarriedorgandistributionafterpoaconitumalkaloid;metabolitesafterivaconitine,mesaconitineandhypaconitine;eliminationafteriv.aconitine,mesaconitine,hypaconitinebythemethod.2ThestudyoftoxicokineticsafterpoaconitumalkaloidPoaconitumalkaloidinasingledose,thetoxicokineticparameterswereestimatedbythe3p97program(designedbyChinesePharmacologicalSociety).Accordingtothecompartmentmodeljudgmentprinciple,wechosethemostsuitablecompartmentmodel.AconitinewasatwocompartmentModelafterpo.Themajortoxicokineticparametersareasfollow.T1/2alpha=3.326±1.564min,T1/2beta=886.609±242.136min,t1/2Ka=2.5192±0.846min,AUC=86557.852±9462.485(ng/ml)×min,T(peak)=6.989±1.546min,CL(s)=0.000004±0.000001mg/kg/min/(ng/ml),C(max)=83.5489±10.4591ng/ml.MesaconitinewasatwocompartmentModelafterpo.Themajortoxicokineticparametersareasfollow.T1/2alpha=15.4989±4.8712min,t1/2Ka=3.618±1.254min,T1/2beta=1255.8081±684.891min,Tpeak=15.782±7.541min,Cmax=202.983±30.781ng/ml,AUC=297212.38±74641.91(ng/ml)×min,CL(s)=