Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry
Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry
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DOI：
10.1002/bmc.1712
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发表时间：
2012-05-01
影响因子：
1.8
通讯作者：
Yoo, Sun Dong
中科院分区：
文献类型：
--
作者：
Kim, Min Gi;Shin, Beom Soo;Yoo, Sun Dong
本研究建立了一种快速灵敏的高效液相色谱-电喷雾电离串联质谱仪(LC-MS/MS)测定小鼠血浆中[6]-姜辣素的方法，并将其应用于小鼠体内的药动学研究。用乙腈沉淀蛋白质，以乙腈和含0.1%甲酸的水(80：20v/v)为流动相进行等度洗脱。多反应监测基于[6]-姜辣素的m/z=277.2->；177.1和非伊夫胺(内标)的294.2->；137.1的转变。方法的特异性、线性、回收率、准确度、精密度和稳定性均得到验证。在10~10,000 ng/mL浓度范围内线性关系良好(r>；=0.9988)。用小鼠血浆(20亩L)定量的下限为10 ng/mL。该方法已成功地用于小鼠静脉注射1.5、3和6 mg/kg姜辣素后的药动学研究。[6]-姜辣素的药物动力学在所研究的剂量范围内呈线性关系，表现为药物浓度-时间曲线下面积(AUCinf)的线性增加，而全身清除量(CLS)、分布体积(VSS)和消除半衰期(T1/2)随剂量的变化不显著。版权所有(C)2011 John Wiley&Sons，Ltd.
This study describes the development of a rapid and sensitive high-performance liquid chromatographyelectrospray ionization tandem mass spectrometry (LC-MS/MS) assay for the quantification of [6]-gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 -> 177.1 for [6]-gingerol and 294.2 -> 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10-10,000 ng/mL (r >= 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 mu L). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]-gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]-gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration-time curve (AUCinf) with no significant change in the systemic clearance (Cls), volume of distribution (Vss) and elimination half-life (t1/2) as a function of dose. Copyright (c) 2011 John Wiley & Sons, Ltd.