Simultaneous Determination of Deoxypodophyllotoxin and Its Major Metabolites in Rat Plasma by a Sensitive LC-MS/MS Method and Its Application in a Pharmacokinetic Study
Simultaneous Determination of Deoxypodophyllotoxin and Its Major Metabolites in Rat Plasma by a Sensitive LC-MS/MS Method and Its Application in a Pharmacokinetic Study
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灵敏 LC-MS/MS 法同时测定大鼠血浆中脱氧鬼臼毒素及其主要代谢物及其在药代动力学研究中的应用
DOI：
10.1007/s10337-015-2992-x
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发表时间：
2016-01-01
期刊：
影响因子：
1.7
通讯作者：
Liu, Xiaodong
中科院分区：
文献类型：
--
作者：
Liu, Fei;Chen, Yang;Liu, Xiaodong
本研究的目的是建立和验证一种快速、灵敏的液相色谱-串联质谱法定量测定大鼠血浆中脱氧鬼臼毒素（DPT）及其主要代谢产物（M1、M2、M7）的方法。地西泮用作内标。该方法包括用乙酸乙酯进行简单的液-液萃取。在Shim-pack VP-ODS分析柱（2.0 mm x 150 mm，5 μ m）上进行色谱分离，使用由乙腈和水（含0.1%甲酸）组成的移动的相进行梯度洗脱，流速为0.2 mL min（-1）。通过正电喷雾电离接口以多反应监测模式进行检测。在研究范围内，所有分析物的校准曲线均呈线性。DPT、M1、M2和M7的定量下限分别为7.734 ng mL（-1）、1.973 ng mL（-1）、7.969 ng mL（-1）和1.973 ng mL（-1）。日内和日间精密度值小于10.59%，准确度范围为-6.787%至12.74%。分析物的萃取回收率高于90%，在该方法中没有观察到明显的基质效应。该方法已成功应用于DPT及其主要代谢物在大鼠血浆中的药代动力学研究。
The purpose of this study is to develop and validate a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantification of deoxypodophyllotoxin (DPT) and its major metabolites (M1, M2, M7) in rat plasma. Diazepam was used as the internal standard. The method involves a simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Shim-pack VP-ODS analytical column (2.0 mm x 150 mm, 5 mu m) with gradient elution using a mobile phase consisting of acetonitrile and water (containing 0.1 % formic acid) at a flow rate of 0.2 mL min(-1). The detection was performed by multiple reaction monitoring mode via a positive electrospray ionization interface. The calibration curves were linear for all analytes over investigated range. The lower limits of quantification were 7.734 ng mL(-1) for DPT, 1.973 ng mL(-1) for M1, 7.969 ng mL(-1) for M2, and 1.973 ng mL(-1) for M7, respectively. The intra- and inter-day precision values were less than 10.59 %, and the accuracy ranged from -6.787 to 12.74 %. The extraction recoveries of the analytes were higher than 90 % and in this method no apparent matrix effect was observed. The validated method was successfully applied to pharmacokinetic study of DPT and its main metabolites in rat plasma.