天麻素和葛根素在大鼠体内联合应用的药动学研究(1)
[摘要]建立同时测定天麻素及其代谢产物天麻苷元、葛根素和内标对羟基苯乙醇(Tyr)4种成分在大鼠血浆中药物浓度的HPLC方法，并应用该法研究单独或合并静脉注射及灌胃给药天麻素、葛根素后，三者在大鼠体内药代动力学过程及相互影响。以Tyr为内标，血浆样品经甲醇沉淀蛋白后，上清液用N2吹干，残渣用乙腈-0.05%磷酸(20∶80)复溶后，以乙腈-0.05%磷酸水为流动相梯度洗脱，用AgilentZORBAXSB-AqC18(4.6mm×150mm，5μm)色谱柱分离，在221nm处测定天麻素、天麻苷元和内标，250nm处测定葛根素。单独或合并给药天麻素、葛根素后，检测大鼠血浆中三者浓度，用WinNonlin5.2药动学软件和SPSS17.0软件分别计算各给药组药动学参数并进行统计分析，比较单独或合并给药后天麻素、葛根素药动学过程。天麻素、天麻苷元和葛根素低、中、高浓度及内标对羟基苯乙醇的绝对回收率均>77.20%;天麻素、天麻苷元、葛根素分别在0.10～101，0.03～7.58，0.05～5.98mg·L-1具有良好的线性(r>0.9996，n=5)，三者定量下限分别为0.10，0.03，0.05mg·L-1，日内及日间精密度均<12%，准确度85.61%～110.3%，且测定物在整个分析过程中稳定。结果表明，天麻素和葛根素联合给药后，大鼠体内主要药代动力学参数(AUC，Cmax，T1/2，Tmax，MRT)与单独给药后有显著性差异。无论是灌胃还是静脉注射，清除率(CL)降低，平均滞留时间(MRT)延长;相对生物利用度均有提高，尤以灌胃组效果显著，其中灌胃天麻素合用组为单用组的1.5倍，灌胃葛根素合用组为单用组的10.7倍。天麻素和葛根素合用后能相互促进吸收，降低消除速率，增加体内滞留时间。该法可同时测定大鼠体内天麻素、天麻苷元和葛根素血药浓度和药动学，且方法准确，操作简便。
, 百拇医药
[关键词]天麻素;天麻苷元(对羟基苯甲醇);对羟基苯乙醇;葛根素;RP-HPLC;药代动力学;大鼠血浆
Pharmacokineticstudyoncombinedapplicationofgastrodinandpuerarininrats
JIANGLi/1，YULan-bin/1，XUGuo-liang/1，ZHANGQi-yun/1，YANXiao-jun/1，WANGYu-rong2*
(1.ResearchCenterforDifferentiationandDevelopmentofBasicTraditionalChineseMedicineTheory，JiangxiUniversityofTraditionalChineseMedicine，Nanchang330004，China;
, 百拇医药
2.SchoolofChineseMateriaMedica，BeijingUniversityofChineseMedicine，Beijing100102，China)
[Abstract]ToestablishaHPLCmethodforsimultaneouslydeterminingplasmaconcentrationsofgastrodin(Gas)anditsmetaboliteshydroxybenzylalcohol(HBA)，puerarin(Pur)andinternalstandard(IS)p-hydroxyphenylethanol(Tyr)inratsandstudyingthepharmacokineticprocessandinteractionsofgastrodinandpuerarinaftersingleandcombinedintravenousinjectionandoraladministration.WithTyrastheinternalstandard，plasmasampleswereprocessedwithmethanolforproteinprecipitation，supernatantwasdriedwithN2，andresidueswerere-dissolvedwithacetonitrile-0.05%phosphoricacid(20∶80).ChromatographywascarriedoutonanAgilentZORBAXSB-AqC18column(4.6mm×250mm，5μm)，withacetonitrile-0.05%phosphoricacidasthegradientmobilephaseforthegradientelution.TheUVdetectorwavelengthwassetat221nmforGasHBAandISand250nmforPur.AfterthesingleorcombinedadministrationofGasandPur，theirplasmaconcentrationsinratsweredetected.WinNonlin5.2pharmacokineticsoftwareandSPSS17.0softwarewereusedtorespectivelycalculatepharmacokineticparametersofeachgroup，makeastatisticalanalysisandcomparethepharmacokineticprocessesofGasandPurafterthesingleorcombinedadministration.Accordingtotheresults，theabsoluterecoveriesbetweenlow，mediaandhighconcentrationsofGas，HBAandPurandISaswellasTyrweremorethan77.20%，withagoodlinearity(r>0.9996，n=5)forGas，HBAandPurwithinconcentrationrangesof0.10-101，0.03-7.58and0.05-5.98mg·L-1，respectively.ThelowerlimitsofquantificationforGas，HBAandPurwere0.10，0.03，0.05mg·L-1，respectively.Theirintra-dayandinter-dayprecisionswerelessthan12%，withtheaccuracybetween85.61%-110.3%.AllofthethreesubstancesandISwerestableduringthewholeanalysisprocess.Thefindingsshowedsignificantdifferencesinthemaininvivopharmacokineticparametersinrats(AUC，Cmax，T1/2，Tmax，MRT)afterthesingleandcombinedadministrationofGasandPur.Eitheraftertheoraladministrationoraftertheintravenousinjection，parametersshowedalowerclearancerate(CL)，longermeanresidencetime(MRT)andhigherrelativebioavailability，especiallyaftertheoraladministration.Specifically，therelativebioavailabilityofthecombinedoraladministrationofPurwas10.7timesofthatofthesingleadministration，whilethatofGaswas1.5timesofthatofthesingleadministration.ThecombinedadministrationofGasandPurcanpromotetheabsorption，decreasetheeliminationrateandprolongthemeanresidencetime.ThemethodissimpleandaccurateandcanbeappliedinthesimultaneousdeterminationofplasmaconcentrationsofGas，HBAandPurinratsandthepharmacokineticstudies., http://www.100md.com(姜丽 余兰彬 徐国良 张启云 严小军 王玉蓉)
, 百拇医药
[关键词]天麻素;天麻苷元(对羟基苯甲醇);对羟基苯乙醇;葛根素;RP-HPLC;药代动力学;大鼠血浆
Pharmacokineticstudyoncombinedapplicationofgastrodinandpuerarininrats
JIANGLi/1，YULan-bin/1，XUGuo-liang/1，ZHANGQi-yun/1，YANXiao-jun/1，WANGYu-rong2*
(1.ResearchCenterforDifferentiationandDevelopmentofBasicTraditionalChineseMedicineTheory，JiangxiUniversityofTraditionalChineseMedicine，Nanchang330004，China;
, 百拇医药
2.SchoolofChineseMateriaMedica，BeijingUniversityofChineseMedicine，Beijing100102，China)
[Abstract]ToestablishaHPLCmethodforsimultaneouslydeterminingplasmaconcentrationsofgastrodin(Gas)anditsmetaboliteshydroxybenzylalcohol(HBA)，puerarin(Pur)andinternalstandard(IS)p-hydroxyphenylethanol(Tyr)inratsandstudyingthepharmacokineticprocessandinteractionsofgastrodinandpuerarinaftersingleandcombinedintravenousinjectionandoraladministration.WithTyrastheinternalstandard，plasmasampleswereprocessedwithmethanolforproteinprecipitation，supernatantwasdriedwithN2，andresidueswerere-dissolvedwithacetonitrile-0.05%phosphoricacid(20∶80).ChromatographywascarriedoutonanAgilentZORBAXSB-AqC18column(4.6mm×250mm，5μm)，withacetonitrile-0.05%phosphoricacidasthegradientmobilephaseforthegradientelution.TheUVdetectorwavelengthwassetat221nmforGasHBAandISand250nmforPur.AfterthesingleorcombinedadministrationofGasandPur，theirplasmaconcentrationsinratsweredetected.WinNonlin5.2pharmacokineticsoftwareandSPSS17.0softwarewereusedtorespectivelycalculatepharmacokineticparametersofeachgroup，makeastatisticalanalysisandcomparethepharmacokineticprocessesofGasandPurafterthesingleorcombinedadministration.Accordingtotheresults，theabsoluterecoveriesbetweenlow，mediaandhighconcentrationsofGas，HBAandPurandISaswellasTyrweremorethan77.20%，withagoodlinearity(r>0.9996，n=5)forGas，HBAandPurwithinconcentrationrangesof0.10-101，0.03-7.58and0.05-5.98mg·L-1，respectively.ThelowerlimitsofquantificationforGas，HBAandPurwere0.10，0.03，0.05mg·L-1，respectively.Theirintra-dayandinter-dayprecisionswerelessthan12%，withtheaccuracybetween85.61%-110.3%.AllofthethreesubstancesandISwerestableduringthewholeanalysisprocess.Thefindingsshowedsignificantdifferencesinthemaininvivopharmacokineticparametersinrats(AUC，Cmax，T1/2，Tmax，MRT)afterthesingleandcombinedadministrationofGasandPur.Eitheraftertheoraladministrationoraftertheintravenousinjection，parametersshowedalowerclearancerate(CL)，longermeanresidencetime(MRT)andhigherrelativebioavailability，especiallyaftertheoraladministration.Specifically，therelativebioavailabilityofthecombinedoraladministrationofPurwas10.7timesofthatofthesingleadministration，whilethatofGaswas1.5timesofthatofthesingleadministration.ThecombinedadministrationofGasandPurcanpromotetheabsorption，decreasetheeliminationrateandprolongthemeanresidencetime.ThemethodissimpleandaccurateandcanbeappliedinthesimultaneousdeterminationofplasmaconcentrationsofGas，HBAandPurinratsandthepharmacokineticstudies., http://www.100md.com(姜丽 余兰彬 徐国良 张启云 严小军 王玉蓉)