液相色谱-串联质谱法测定晚期实体癌患者静脉滴注紫杉醇胶束后的药动学

发布时间：2018-06-22 22:32

  本文选题：紫杉醇 + 色谱法　； 参考：《中国新药与临床杂志》2015年11期

【摘要】：目的建立测定人血浆中紫杉醇浓度的液相色谱-串联质谱(LC-MS/MS)法。方法 8例晚期实体癌患者,进行单次静脉滴注注射用紫杉醇胶束(300 mg·m-2),采集血浆样本并测定其中紫杉醇的浓度。血浆样本以氘5-紫杉醇为内标,血浆经直接沉淀后进样分析,选用CAPCELL PAK C18 MGIII(100 mm×2.0 mm,5μm)为分析柱,以0.2%甲酸的水溶液-乙腈溶液=40∶60(V/V)为流动相,流速为0.4 m L·min-1。选用三重四级杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,正离子方式。并采用Phoenix Win Nonlin 6.2软件对数据进行处理,计算药动学参数。结果血液中紫杉醇的线性范围10~20 000μg·L-1。日内、日间RSD均小于8%,平均提取回收率在89.5%~97.7%范围内。内标校正基质因子为0.888 7~1.033,RSD4%。应用此法,检测8例晚期实体癌患者静脉滴注注射用紫杉醇胶束(300 mg·m-2)所得主要药动学参数:ρmax为(3 872±1 062)μg·L-1,AUC0-∞为(14 603±3 390)μg·h·L-1,t1/2为(18.3±6.4)h,CL为(22.0±5.0)L·h-1·m-2。结论建立的LC-MS/MS测定人血浆中紫杉醇浓度的方法灵敏度高、专一性好、操作简单。
[Abstract]:Objective to establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of paclitaxel in human plasma. Methods eight patients with advanced solid carcinoma were treated with paclitaxel micelle (300 mg m-2) for single intravenous infusion. Plasma samples were collected and the concentrations of paclitaxel were measured. Deuterium 5- paclitaxel was used as internal standard, plasma was analyzed by direct precipitation, CAPCELL PAK C18 mg III (100 mm 脳 2.0 mm ~ 5 渭 m) was used as the analytical column, and the mobile phase was 0.2% formic acid-acetonitrile solution 40: 60 (V / V), the flow rate was 0.4 mL / min ~ (-1). The multiple reaction monitoring (MRM) scanning mode, electrospray ionization source and positive ion mode were used to monitor the triple four-bar series mass spectrometer. The data were processed by Phoenix win Nonlin 6.2 software and the pharmacokinetic parameters were calculated. Results the linear range of paclitaxel in blood was 100.000 渭 g / L ~ (-1). The inter-day RSD was less than 8 and the average recovery was in the range of 89.5% or 97.7%. The calibration matrix factor of internal standard was 0.888 ~ 1.033% RSD _ 4. Using this method, the pharmacokinetic parameters of paclitaxel micelle (300mg m-2) for intravenous infusion in 8 patients with advanced solid carcinoma were determined as follows: 蟻 max was (3 872 卤1 062) 渭 g / L ~ (-1) AUC _ (0- 鈭，

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