液相色譜-串聯(lián)質(zhì)譜法測(cè)定晚期實(shí)體癌患者靜脈滴注紫杉醇膠束后的藥動(dòng)學(xué)
發(fā)布時(shí)間:2018-06-22 22:32
本文選題:紫杉醇 + 色譜法 ; 參考:《中國(guó)新藥與臨床雜志》2015年11期
【摘要】:目的建立測(cè)定人血漿中紫杉醇濃度的液相色譜-串聯(lián)質(zhì)譜(LC-MS/MS)法。方法 8例晚期實(shí)體癌患者,進(jìn)行單次靜脈滴注注射用紫杉醇膠束(300 mg·m-2),采集血漿樣本并測(cè)定其中紫杉醇的濃度。血漿樣本以氘5-紫杉醇為內(nèi)標(biāo),血漿經(jīng)直接沉淀后進(jìn)樣分析,選用CAPCELL PAK C18 MGIII(100 mm×2.0 mm,5μm)為分析柱,以0.2%甲酸的水溶液-乙腈溶液=40∶60(V/V)為流動(dòng)相,流速為0.4 m L·min-1。選用三重四級(jí)桿串聯(lián)質(zhì)譜儀的多重反應(yīng)監(jiān)測(cè)(MRM)掃描方式進(jìn)行監(jiān)測(cè),電噴霧離子化源,正離子方式。并采用Phoenix Win Nonlin 6.2軟件對(duì)數(shù)據(jù)進(jìn)行處理,計(jì)算藥動(dòng)學(xué)參數(shù)。結(jié)果血液中紫杉醇的線性范圍10~20 000μg·L-1。日內(nèi)、日間RSD均小于8%,平均提取回收率在89.5%~97.7%范圍內(nèi)。內(nèi)標(biāo)校正基質(zhì)因子為0.888 7~1.033,RSD4%。應(yīng)用此法,檢測(cè)8例晚期實(shí)體癌患者靜脈滴注注射用紫杉醇膠束(300 mg·m-2)所得主要藥動(dòng)學(xué)參數(shù):ρmax為(3 872±1 062)μg·L-1,AUC0-∞為(14 603±3 390)μg·h·L-1,t1/2為(18.3±6.4)h,CL為(22.0±5.0)L·h-1·m-2。結(jié)論建立的LC-MS/MS測(cè)定人血漿中紫杉醇濃度的方法靈敏度高、專一性好、操作簡(jiǎn)單。
[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 鹵1 062) 渭 g / L ~ (-1) AUC _ (0- 鈭,
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