高通量分析紫杉醇在动物体内的药动学及组织分布  

Pharmacokinetics and tissue distribution of paclitaxel injection based high throughput analysis

作　　者：李金银[1] 房晶[2] 李文学[2] 陈建明[2] 毛士龙[1] 范国荣[2] 

机构地区：[1]上海市徐汇区中心医院药械科,200031 [2] 第二军医大学药学院药物分析学教研室

出　　处：《中国医药》2014年第12期1833-1837,共5页China Medicine

摘　　要：目的 建立基于96孔板的高通量测定SD大鼠血浆和荷瘤小鼠组织中紫杉醇浓度的方法.方法 将SD大鼠血浆样品、荷瘤小鼠组织样品及内标物多西他赛置于96孔板中,采用96/384道半自动液体移液器取液进行高通量的液液萃取,高效液相色谱-串联质谱（LC/MS/MS）法测定各生物样品的紫杉醇浓度.结果 紫杉醇的线性范围为2 ～ 500 μg/L,最低定量下限为2μg/L.在SD大鼠血浆中,紫杉醇的半衰期、平均滞留时间、药时曲线下面积、药时曲线下总面积、药物清除率、表观分布容积分别为（6.3 ±0.4）h、（7.16 ±0.13）h、（3 070 ±201）（h· μg）/L、（3246±199）（h· μg）/L、（1.55±0.09）L/（h·kg）、（13±8）L/kg.荷瘤小鼠尾静脉注射紫杉醇注射液7.5 mg/kg后0.5、1、2、4、8h,紫杉醇在小鼠心、肝、脾、肺、肾、肿瘤中含量差异有统计学意义（P＜0.05）.结论 LC/MS/MS法专一、准确、稳定、简便并且实现了高通量分析,适用于紫杉醇的SD大鼠药动学和荷瘤小鼠组织分布研究.Objective To develop a high-throughput analytical method based on 96-well plate for the determination of paclitaxel.Methods Plasma or tissue samples and docetaxel （internal standard,IS） were collected in 96-well plates by liquid-liquid extraction; most liquid transfer steps were performed by 96/384-channel semiautomatic pipetting tools.The concentrations of paclitaxel in biological samples were determined by LC/MS/MS Method.Results The calibration curves were linear over the range of 2 500 μg/L.The lower limit of quantitation was 2 μg/L.The main pharmacokinetic parameters of paclitaxel injection in SD rats were as follows：half time was （6.3 ± 0.4） h,mean rasidence time was （7.16 ± 0.13） h,area under the time concentration curve （0 to 24h） was （3 070 ±201）h · μg/L,area under the time concentration curve（0 to ∞） was（3 246 ± 199）h · μg/L,clearance was （1.55 ± 0.09） L/（h · kg）,apparent volume of distribution was （13 ± 8） L/kg.There were higher concentrations in livers,kidney,spleen,lung,tumor and smaller in heart and blood and targeting performance in tumor rats.Conclusion The method is sensitive,accurate and convenient.

关 键 词：紫杉醇 96孔板 药动学 串联质谱法 色谱法 

分 类 号：R965.2[医药卫生—药理学]