Hooshfar Shirin, Linzey Michael R, Wu Daqing, Gera Lajos, Mamouni Kenza, Li Xin, Chen Yanhua, Yang Yang, Olorunyolemi Oluwasegun, Bartlett Michael G
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA, USA.
Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA.
Biomed Chromatogr. 2018 Feb;32(2). doi: 10.1002/bmc.4064. Epub 2017 Sep 12.
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.
建立并验证了一种简单且灵敏的液相色谱/电喷雾电离串联质谱法（LC-ESI-MS/MS），用于测定大鼠血浆和组织（肝脏、肾脏和股骨）中两种高度亲脂性抗癌候选药物LG1980和GH501。采用液-液萃取法从大鼠血浆和组织匀浆中提取LG1980和GH501。该方法在血浆中对GH501和血浆及肝脏中的LG1980的线性范围为1.0-200.0 ng/mL。在其他组织匀浆中，两种分析物的线性范围均为2.0-400.0 ng/mL。该方法的验证结果为相对标准偏差在15%以内，相对误差在15%以内，回收率一致。该方法已成功应用于两项针对LG1980和GH501的临床前研究，以测定静脉注射化合物后24小时内大鼠血浆、肝脏、肾脏和骨骼中的药物浓度。
