Sensitive liquid chromatography/tandem mass spectrometry method for the determination of two novel highly lipophilic anticancer drug candidates in rat plasma and tissues.
Sensitive liquid chromatography/tandem mass spectrometry method for the determination of two novel highly lipophilic anticancer drug candidates in rat plasma and tissues.
复制标题
灵敏液相色谱/串联质谱法测定大鼠血浆和组织中两种新型高亲脂性抗癌药物候选物。
DOI：
10.1002/bmc.4064
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Bartlett,MichaelG
中科院分区：
文献类型：
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作者：
Hooshfar,Shirin;Linzey,MichaelR;Wu,Daqing;Gera,Lajos;Mamouni,Kenza;Li,Xin;Chen,Yanhua;Yang,Yang;Olorunyolemi,Oluwasegun;Bartlett,MichaelG
开发并验证了一种简单灵敏的液相色谱/电喷雾串联质谱（LC-ESI-MS/MS）方法，用于测定大鼠血浆和组织（肝、肾和股骨）中的两种高度亲脂性抗癌候选药物LG 1980和GH501。采用液-液萃取法从大鼠血浆和组织匀浆中萃取LG 1980和GH501。该方法提供的血浆中GH501和血浆和肝脏中LG 1980的线性范围为1.0-200.0 ng/mL。对于其他组织匀浆中的两种分析物，线性范围为2.0-400.0 ng/mL。该方法经验证，精密度在15%相对标准偏差范围内，准确度在15%相对误差范围内，回收率一致。该方法已成功应用于LG 1980和GH501的两项临床前研究，以测定静脉注射化合物后24 h内大鼠血浆、肝脏、肾脏和骨骼中的浓度。
A simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS) method was developed and validated for determination of two highly lipophilic anticancer drug candidates, LG1980 and GH501, in rat plasma and tissues (liver, kidney and femur bones). LG1980 and GH501 were extracted from rat plasma and tissue homogenates using liquid–liquid extraction. The method provided a linear range of 1.0–200.0 ng/mL for GH501 in plasma and LG1980 in plasma and liver. For both analytes in other tissue homogenates the linear range was 2.0–400.0 ng/mL. The method was validated with precision within 15% relative standard deviation, accuracy within 15% relative error and a consistent recovery. This method has been successfully applied in two preclinical studies for LG1980 and GH501 to determine their concentrations in rat plasma, liver, kidney and bone over 24 h after intravenous injection of compounds.