高效液相色谱-串联质谱法测定人血浆中氯法拉滨的浓度

张春燕 朱宝英 赵立波 闫美玲 方翼 李玉珍

中国药学杂志 ›› 2010, Vol. 45 ›› Issue (19) : 1492-1495.

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中国药学杂志 ›› 2010, Vol. 45 ›› Issue (19) : 1492-1495.
论 著

高效液相色谱-串联质谱法测定人血浆中氯法拉滨的浓度

  • 张春燕1,朱宝英2,赵立波1, 闫美玲3,方翼1,李玉珍1
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Determination of Clofarabine in Human Plasma by LC-MS/MS

  • ZHANG Chun-yan1, ZHU Bao-ying2,ZHAO Li-bo1,YAN Mei-ling3,FANG Yi1,LI Yu-zhen1
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摘要

目的 建立高效液相色谱-串联质谱法(LC-MS/MS)测定人血浆中氯法拉滨浓度。方法 采用API3000串联质谱仪及Shimadzu系列液相色谱仪进行检测。血浆样品经乙酸乙酯提取处理,以克拉屈滨为内标。色谱柱为Thermo C18柱(4.6 mm×150 mm,5 μm),流动相为乙腈-水(250∶3,其中含4 mmol的乙酸铵和0.3%的甲酸),流速为0.5 mL·min-1。氯法拉滨和克拉屈滨的MRM扫描离子通道m/z分别为304.0→170.0,286.1→170.0。进样体积为20 μL,每个样品的分析时间为5 min。结果 氯法拉滨和克拉屈滨保留时间分别为4.00,4.11 min。氯法拉滨在10~2 000 ng·mL-1内线性关系良好(r=0.999 5),日内、日间RSD均低于9.60%,准确度为101.10%~102.94%。结论 本法样品预处理简便快速,检测准确、灵敏、专一,适用于氯法拉滨药动学的研究。

Abstract

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of clofarabine in human plasma. METHODS The drug was determinated by LC-MS/MS using electrospray ionization. The plasma samples were extracted with ethyl acetate. Cladribine was the internal standard (IS). The analytical column was Thermo C18 column (4.6 mm×150 mm,5 μm). The mobile phase consisted of acetonitrile-water (250∶3,Which contains 4 mmol of ammonium acetate and 0.3% formic acid) at a flow rate of 0.5 mL·min-1. Clofarabine and cladribine were detected on multiple reaction monitoring (MRM) by the transitions from the precursor to the product ion (m/z 304.0/170.0 and m/z 286.1/170.0). The injection volume was 20 μL and the total run time was 5.0 min. RESULTS Calibration curve showed good linearity in the range of 10-2 000 ng·mL-1 (r=0.999 5). The intra-batch and inter-batch precisions (RSD) were all less than 9.60% and the accuracy was within 101.10%-102.94%. CONCLUSION The retention time of cladribine and clofarabine were 4.00 and 4.11 min. The established LC-MS/MS method is sensitive,accurate and simple for the determination of clofarabine in human plasma. It is suitable for the pharmacokinetics of clofarabine.

关键词

氯法拉滨 / 高效液相色谱-串联质谱法 / 血浆浓度

Key words

clofarabine / LC-MS/MS / drug plasma concentration

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导出引用
张春燕 朱宝英 赵立波 闫美玲 方翼 李玉珍. 高效液相色谱-串联质谱法测定人血浆中氯法拉滨的浓度[J]. 中国药学杂志, 2010, 45(19): 1492-1495
ZHNG Chun-yn;ZHU o-ying;ZHO Li-o;YN Mei-ling;FNG Yi;LI Yu-zhen. Determination of Clofarabine in Human Plasma by LC-MS/MS[J]. Chinese Pharmaceutical Journal, 2010, 45(19): 1492-1495

参考文献


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