SD大鼠体内各组织中银杏内酯B的LC-MS/MS测定
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摘要
建立了液相色谱-串联质谱(LC-MS/MS)法测定SD大鼠心、肝、脾、肺、肾、骨骼肌、小肠、性腺(睾丸、卵巢)、脂肪和脑10种组织中的银杏内酯B。以白果内酯为内标,采用ESI源负离子模式、多反应监测(MRM)进行定量分析,监测离子对m/z 423.1→m/z 367.1(银杏内酯B)和m/z 325.2→m/z 163.2(白果内酯)。以大鼠肝组织作为代表性基质进行方法学验证,结果表明银杏内酯B在20~5 000 ng/g范围内线性关系良好,方法回收率90.26%~102.99%,日内、日间RSD小于8.6%。采用该法考察雄性SD大鼠尾静脉注射银杏内酯B注射液(10 mg/kg)后的组织分布情况,结果显示,各组织中的药物浓度随着给药时间的延长而迅速衰减;同时该药更易蓄积在血流量较大的肝肾组织中。此外,该药可穿透血脑屏障进入脑组织。
A LC-MS/MS method was established for the determination of ginkgolide B in SD rat tissues,including heart,liver,spleen,lung,kidney,skeletal muscle,intestine,gonads(testicle and ovary),fat and brain.Bilobalide was selected as the internal standard.The detection was conducted under negative ionization mode with an electrospray ionization(ESI) interface.A multiple reaction monitoring mode was optimized with the transitions of m/z 423.1→m/z 367.1(ginkgolide B) and m/z 325.2→m/z 163.2(bilobalide).When liver was chosen as the prime matrix,the calibration curve was linear in the range of 20—5 000 ng/g.The method recoveries were 90.26%—102.99%,with RSDs less than 8.6%.The validated method was applied to investigate the tissue distribution of ginkgolide B in male SD rats followed by intravenous administration of test preparation at the dose of 10 mg/kg.The drug concentration in every tissue decreased rapidly with the time of administration and ginkgolide B tended to accumulate in well-perfused organs like liver and kidney.It was noteworthy that ginkgolide B could penetrate blood-brain barrier.
A LC-MS/MS method was established for the determination of ginkgolide B in SD rat tissues,including heart,liver,spleen,lung,kidney,skeletal muscle,intestine,gonads(testicle and ovary),fat and brain.Bilobalide was selected as the internal standard.The detection was conducted under negative ionization mode with an electrospray ionization(ESI) interface.A multiple reaction monitoring mode was optimized with the transitions of m/z 423.1→m/z 367.1(ginkgolide B) and m/z 325.2→m/z 163.2(bilobalide).When liver was chosen as the prime matrix,the calibration curve was linear in the range of 20—5 000 ng/g.The method recoveries were 90.26%—102.99%,with RSDs less than 8.6%.The validated method was applied to investigate the tissue distribution of ginkgolide B in male SD rats followed by intravenous administration of test preparation at the dose of 10 mg/kg.The drug concentration in every tissue decreased rapidly with the time of administration and ginkgolide B tended to accumulate in well-perfused organs like liver and kidney.It was noteworthy that ginkgolide B could penetrate blood-brain barrier.
引文
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[2]Chi CL,Shen DF,Wang PJ,et al.Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke[J].Int J Clin Exp Med,2015,8(3):3522—3529.
[3]杨鹏飞,陈卫东.银杏内酯B药理作用研究进展[J].安徽中医药大学学报,2012,31(5):86—90.
[4]蔡晓蕾,陈卫东.银杏内酯B剂型研究进展[J].安徽中医学院学报,2013,32(1):86—90.
[5]Wang J,Ouyang J,Liu Y,et al.Development of a sensitive LC-MS/MS method for the determination of bilobalide in rat plasma with special consideration of ex vivo bilobalide stability:application to a preclinical pharmacokinetic study[J].J Pharm Biomed Anal,2014,95:238—244.
[6]杨赴云,王景田.银杏内酯A,B在家兔体内的药代动力学研究[J].中国药学杂志,2000,35(8):541—543.
[7]Song H,Bu F,Wei C,et al.Pharmacokinetics of ginkgolide B injection in Beagle dogs[J].Arzneimittel-Forschung,2012,62(12):595—598.
[8]宋玉乔,廖杰,李宁,等.液相色谱-串联质谱法测定人血浆中银杏内酯B的含量[J].现代科学仪器,2010:153—155.
[9]Chen WD,Liang Y,Xie L,et al.Pharmacokinetics of the ginkgo B following intravenous administration of ginkgo B emulsion in rats[J].Biol Pharm Bull,2007,30(1):1—5.
[10]Wang S,Ouyang B,Aa J,et al.Pharmacokinetics and tissue distribution of ginkgolide A,ginkgolide B,and ginkgolide K after intravenous infusion of ginkgo diterpene lactones in a rat model[J].J Pharm Biomed Anal,2016,126:109—116.
[11]刘冰洋,刘有平,王鑫,等.LC-MS/MS法测定Wistar大鼠组织中银杏内酯B的浓度[J].沈阳药科大学学报,2012,29(7):541—545.
[12]Lan K,Li XJ,Du G,et al.Characterizations of the hydrolyzed products of ginkgolide A and ginkgolide B by liquid chromatography coupled with mass spectrometry[J].J Pharm Biomed Anal,2016,118:113—122.
[13]Wang DL,Peng DY,Tao XH,et al.The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma[J].J Asian Nat Prod Res,2013,15(4):337—343.