HPLC-MS/MS method to determine genipin in rat plasma after hydrolysis with sulfatase and its application to a pharmacokinetic study
HPLC-MS/MS method to determine genipin in rat plasma after hydrolysis with sulfatase and its application to a pharmacokinetic study
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DOI：
10.1002/bmc.1735
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发表时间：
2012-07-01
影响因子：
1.8
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Ding, Yue;Zhang, Tong;Yang, Li
建立了测定大鼠血浆中京尼平硫酸酯酶水解产物的高效液相色谱-串联质谱（LC-MS/MS）方法。京尼平不能直接检测，因为它可以在给药后立即转化为其他形式，如缀合的京尼平。共轭京尼平可被硫酸酯酶水解为京尼平。对水解条件进行了研究。京尼平和内标芍药苷（IS）在反相柱上通过梯度洗脱分离，并在4000 QTrap三重四极杆质谱仪上使用电喷雾离子源检测。使用多反应监测进行定量，对于京尼平和芍药苷，使用跃迁m/z 225.0 -> 122.7和m/z 479.1 -> 449.1的选择的吸收体-产物离子对。该方法在1.368-1368 μ g/L浓度范围内呈线性关系。ng/mL，相关系数为0.9989。日内和日间精密度和准确度均在15%以内。定量下限为1.368？ng/mL。京尼平和芍药苷的回收率分别为53.3%和51.2%。高灵敏度的方法已成功地应用于估计京尼平口服和静脉给药后，大鼠的药代动力学参数。京尼平在大鼠体内的绝对生物利用度为80.2%，为首次报道。版权所有（c）2011约翰威利父子有限公司
A sensitive high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS) method was developed for the quantification of genipin in rat plasma after hydrolysis with sulfatase. Genipin could not be detected directly as it could be transformed into other forms such as conjugated-genipin immediately after administration. The conjugated genipin could be hydrolyzed by sulfatase to genipin. The conditions of hydrolysis were investigated. Genipin and the internal standard, peoniflorin (IS), were separated on a reversed-phase column by gradient elution and detected using an electrospray ion source on a 4000 QTrap triple-quadrupole mass spectrometer. The quantification was performed using multiple reaction monitoring with selected precursor-product ion pairs of the transitions m/z 225.0 -> 122.7 and m/z 479.1 -> 449.1 for genipin and peoniflorin. The assay was linear over the concentration range of 1.368-1368?ng/mL, with correlation coefficients of 0.9989. Intra- and inter-day precisions and accuracy were all within 15%. The lower limit of quantification was 1.368?ng/mL. The recoveries of genipin and peoniflorin were more than 53.3 and 51.2%. The highly sensitive method was successfully applied to estimated pharmacokinetic parameters of genipin following oral and intravenous administration to rats. The absolute bioavailability of genipin was 80.2% in rat, which is the first report. Copyright (c) 2011 John Wiley & Sons, Ltd.