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（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CAPCELLPAKC18MGⅢ（100mm×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0．4mL·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PhoenixWinNonlin6．2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0．8887～1．033，RSD〈4％。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（300mg·m-2）所得主要药动学参数：ρmax为（3872±1062）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。
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（100mm×2.0mm,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 range 10 - 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 0.888 7 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 was （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.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2015年第11期869-873,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
2014年上海市国家创新基金(14C26213100947)
关键词
紫杉醇
色谱法
高压液相
串联质谱法
药动学
paclitaxel
chromatography, high pressure liquid
tandem mass spectrometry
pharmaco-kinetics
