首页> 中文期刊> 《药学与临床研究》 >LC-MS/MS法测定血浆中多西他赛和紫杉醇浓度及在乳腺癌患者中的应用

LC-MS/MS法测定血浆中多西他赛和紫杉醇浓度及在乳腺癌患者中的应用

         

摘要

Objective: To establish an LC-MS/MS method for determining the concentrations of docetax-el and paclitaxel in plasma of breast cancer patients. Methods: Docetaxel and paclitaxel were used as the internal standard for each other. A sample of 100μL human plasma was extracted by using 1 mL of terta-butyl methyl ether. The upper organic layer was dried under nitrogen flow. The residue was reconstituted with mobile phase and then injected for LC-MS/MS analysis. The separation was performed on an Agilent Eclipse XDB-C18 analytical column (100 mm×2.1 mm, 3.5μm) at 40℃. Samples were eluted using a mobile phase consisting of 0.4% formic acid water / 0.4% formic acid acetonitrile solution (20∶80, v/v) at a flow rate of 0.3 mL·min-1. Detection and quantitation were performed by electrospray ionization in the positive ionization mode by multiple reaction monitoring of the transitions at m/z 808.5 → m/z 527.2 for docetaxel and m/z 854.3 → m/z 569.4 for paclitaxel. Results: The linear ranges of docetaxel and paclitaxel were, respectively, 5.0-1000 ng·mL-1 and 1.0-500 ng·mL-1 with LLOQ at 5.0 ng·mL-1 and 1.0 ng·mL-1. The intra-and inter-day RSDs were all within 15% at low, moderate and high concentrations. The mean extract re-coveries were 65.9%-84.3% for docetaxel and 90.4%-106.5% for paclitaxel. Conclusion: The method es-tablished is rapid, sensitive, accurate and reliable for the determination of docetaxel and paclitaxel in hu-man plasma. The method is useful for the therapeutic drug monitoring of docetaxel and paclittaxel, and can be applied in pharmacokinetic study of the drugs in Chinese breast cancer patients.%目的:建立一种快速、灵敏的液相色谱-串联质谱(LC-MS/MS)法检测乳腺癌患者血浆中多西他赛、紫杉醇的浓度。方法:多西他赛和紫杉醇互为内标,血浆样品100μL加入1 mL叔丁基甲醚萃取,分离有机相,以氮气吹干后流动相复溶进样。色谱柱为Agilent Eclipse XDB-C18(2.1 mm×100 mm,3.5μm),流动相为0.4%甲酸水溶液-0.4%甲酸乙腈溶液(20∶80,v/v),流速0.3 mL·min-1,柱温为40℃。采用多反应监测(MRM)进行定量,电喷雾电离源(ESI)正离子方式进行检测,多西他赛与紫杉醇用于定量分析的检测离子对分别为m/z 808.5→m/z 527.2和m/z 854.3→m/z 569.4。结果:多西他赛和紫杉醇的线性范围分别为5.0~1000 ng·mL-1和1.0~500 ng· mL-1,最低检测浓度分别为5.0 ng·mL-1和1.0 ng·mL-1。两药低、中、高三个浓度的批内和批间RSD均<15%,平均提取回收率分别为65.9%~84.3%和90.4%~106.5%。结论:本法快速、准确、灵敏、专属性强,适用于同步测定多西他赛和紫杉醇血药浓度及其在中国乳腺癌患者中的药动学研究。

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