【作者】 茅晓寅； 张梦琪； 周沁逸； 董春霞； 沈薇薇； 刘罡一； 贾晶莹； 余琛； 史美祺；

【Author】 MAO Xiao-yin;ZHANG Meng-qi;ZHOU Qin-yi;DONG Chun-xia;SHEN Wei-wei;LIU Gang-yi;JIA Jing-ying;YU Chen;SHI Mei-qi;Central Laboratory, Shanghai Xuhui Central Hospital;Department of Internal Medicine, Jiangsu Cancer Hospital;

【机构】 上海市徐汇区中心医院中心实验室； 江苏省肿瘤医院内科；

【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）方法。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（300mg·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×2.0mm,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 mL·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 WinNonlin 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10～20000μg·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,RSD<4%。应用此法,对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为:ρmax为（3 872±1 062）μg·L^-1,AUC0-∞为（14603±3390）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,可用于临床药动学的研究。更多还原

【Abstract】 AIM To establish a liquid chromatography-tandem mass spectrometric（LC-MS/MS） method for determination of paclitaxel in human plasma. METHODS Plasma samples were collected from 8 patients with advanced solid cancer after administered intravenous paclitaxel-loaded micelle infusion at a single dose of 300 mg·m^-2. In order to determine the concentration of paclitaxel, plasma samples were spiked with D5-labeled paclitaxel（internal standard,IS） and precipitated by methanol to remove protein before analysis. Chromatographic separation was achieved by a CAPCELL Pak C18 MGIII（100 mm×2.0 mm, 5μm） with an isocratic mobile phase which consisted of 0.2% formic acidin water-acetonitrile（40∶60,V/V）at a flow rate of 0.4 mL·min^-1. The mass spectrometer was operated in a positive electrospray multiple reaction monitoring（MRM） mode. The pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.2. RESULTS The calibration curve was linear over the range10-20 000 μg·L^-1 for paclitaxel. Both inter-and intra-day precision（RSD） were less than 8%. The average recovery was between 89.5% and 97.7%. IS normalized-MF was between 0.8887 and 1.033, RSD was less than 4%. This method was applied successfully to quantify paclitaxel level in plasma of 8 patients with advanced solid cancer who received recommended dose of drugs(300 mg·m^-2) by intravenous infusion for 3 h. The main pharmacokinetic parameters were as follows:ρmax was（3 872±1 062）μg·L^-1, AUC0-∞was（14 603±3 390） μg·h·L^-1, t1/2 is（18.3±6.4） h, CL was（22.0±5.0） L·h-1·m^-2.CONCLUSION The established LC-MS/MS detection method is sensitive, accurate, and simple for the determination of paclitaxel in human plasma. This method was successfully applied in pharmacokinetic study.更多还原