中国医药
中國醫藥
중국의약
CHINA MEDICINE
2014年
12期
1833-1837
,共5页
李金银%房晶%李文学%陈建明%毛士龙%范国荣
李金銀%房晶%李文學%陳建明%毛士龍%範國榮
리금은%방정%리문학%진건명%모사룡%범국영
紫杉醇%96孔板%药动学%串联质谱法%色谱法
紫杉醇%96孔闆%藥動學%串聯質譜法%色譜法
자삼순%96공판%약동학%천련질보법%색보법
Taxol%96-well plates%Pharmacokinetics%Tandem mass spectrometry%Chromatography
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.
目的 建立基于96孔闆的高通量測定SD大鼠血漿和荷瘤小鼠組織中紫杉醇濃度的方法.方法 將SD大鼠血漿樣品、荷瘤小鼠組織樣品及內標物多西他賽置于96孔闆中,採用96/384道半自動液體移液器取液進行高通量的液液萃取,高效液相色譜-串聯質譜(LC/MS/MS)法測定各生物樣品的紫杉醇濃度.結果 紫杉醇的線性範圍為2 ～ 500 μg/L,最低定量下限為2μg/L.在SD大鼠血漿中,紫杉醇的半衰期、平均滯留時間、藥時麯線下麵積、藥時麯線下總麵積、藥物清除率、錶觀分佈容積分彆為(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.荷瘤小鼠尾靜脈註射紫杉醇註射液7.5 mg/kg後0.5、1、2、4、8h,紫杉醇在小鼠心、肝、脾、肺、腎、腫瘤中含量差異有統計學意義(P＜0.05).結論 LC/MS/MS法專一、準確、穩定、簡便併且實現瞭高通量分析,適用于紫杉醇的SD大鼠藥動學和荷瘤小鼠組織分佈研究.
목적 건립기우96공판적고통량측정SD대서혈장화하류소서조직중자삼순농도적방법.방법 장SD대서혈장양품、하류소서조직양품급내표물다서타새치우96공판중,채용96/384도반자동액체이액기취액진행고통량적액액췌취,고효액상색보-천련질보(LC/MS/MS)법측정각생물양품적자삼순농도.결과 자삼순적선성범위위2 ～ 500 μg/L,최저정량하한위2μg/L.재SD대서혈장중,자삼순적반쇠기、평균체류시간、약시곡선하면적、약시곡선하총면적、약물청제솔、표관분포용적분별위(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.하류소서미정맥주사자삼순주사액7.5 mg/kg후0.5、1、2、4、8h,자삼순재소서심、간、비、폐、신、종류중함량차이유통계학의의(P＜0.05).결론 LC/MS/MS법전일、준학、은정、간편병차실현료고통량분석,괄용우자삼순적SD대서약동학화하류소서조직분포연구.
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.
