Simultaneous determination of bentysrepinine (Y101) and its metabolites M8 and M9 in human plasma by UPLC-MS/MS and its application to a pharmacokinetic study
Simultaneous determination of bentysrepinine (Y101) and its metabolites M8 and M9 in human plasma by UPLC-MS/MS and its application to a pharmacokinetic study
复制标题
UPLC-MS/MS同时测定人血浆中bentysrepinine (Y101)及其代谢物M8和M9及其在药代动力学研究中的应用
DOI：
10.1016/j.jpba.2017.12.010
复制
发表时间：
2018-02-20
影响因子：
3.4
通讯作者：
Miao, Liyan
中科院分区：
文献类型：
--
作者：
Liu, Xiaoxue;Huang, Chenrong;Miao, Liyan
建立了一种快速、灵敏的高效液相色谱-串联质谱仪(LC-MS/MS)测定人血浆中抗乙肝病毒新化合物Y101及其代谢物M8和M9的方法。血浆样品在加入帕拉米韦(内标，IS)后用乙腈脱蛋白，并在40℃ACQUITY UPLC BEH C-18柱(2.1 mm x 50 mm，1.7微米)上分离。流动相为水(含5 mM醋酸铵和0.1%甲酸)-乙腈(74：26，v/v)，流速0.3mL/min。检测在Triple Quad5500串联质谱仪上进行，电喷雾电离(ESI)源为正模式。Y101的m/z 490.1->；339.0、代谢物M8的m/z 357.2->；105.2、代谢物M9的m/z 373.1->；105.1和IS的m/z 329.1->；270.2的转变分别通过多反应监测进行定量。用线性回归和1/x(2)加权法对Y101、M8和M9的校正曲线范围分别为1.000~1.000 ng/mL、2.000~2000 ng/mL和0.3000~2000 ng/mL进行了验证。未观察到基质效应和携带效应。Y101、代谢物M8和M9的批内和批间精密度和准确度均在可接受的标准范围内。该方法可快速、简便地测定人血浆中Y101及其代谢物M8和M9。首次将其成功应用于人体药代动力学研究。(C)2017爱思唯尔B.V.保留所有权利。
A rapid and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of a novel anti-HBV compound Y101 and its metabolites M8 and M9 in human plasma. The plasma samples were deproteinated with acetonitrile after addition of Peramivir (internal standard, IS) and separated on a 40 degrees C ACQUITY UPLC BEH C-18 column (2.1 mm x 50 mm, 1.7 mu m). The mobile phase consisted of water (containing 5 mM ammonium acetate and 0.1% formic acid) and acetonitrile (74:26, v/v) at a flow rate of 0.3 mL/min. The detection was performed on a Triple Quad 5500 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive mode. Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 490.1 -> 339.0 for Y101, m/z 357.2 -> 105.2 for metabolite M8, m/z 373.1 -> 105.1 for metabolite M9 and m/z 329.1 -> 270.2 for IS, respectively. The method was validated over the calibration curve range of 1.000-1000 ng/mL for Y101, 2.000-2000 ng/mL for metabolite M8 and 0.3000-300.0 ng/mL for metabolite M9, using linear regression and 1/x(2) weighting. No matrix effect and carryover effect was observed. The intra- and inter-batch precision and accuracy of Y101, metabolite M8 and M9 were all within the acceptable criteria. This method allows a rapid and simple determination of Y101 and its metabolites M8 and M9 in human plasma. It was successfully applied in a pharmacokinetic study in human for the first time. (C) 2017 Elsevier B.V. All rights reserved.