Development of a validated LC-MS/MS method for the determination of ailanthone in rat plasma with application to pharmacokinetic study
Development of a validated LC-MS/MS method for the determination of ailanthone in rat plasma with application to pharmacokinetic study
复制标题
DOI：
10.1016/j.jpba.2014.10.022
复制
发表时间：
2015-01-05
影响因子：
3.4
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Chen, Ang;Qin, Xuan;Wang, Xin
Ailanthone是从中草药臭椿中分离得到的一种天然化合物，因其抗肿瘤活性而备受关注。本研究首次建立了一种简便、灵敏的高效液相色谱-串联质谱法(LC-MS/MS)测定大鼠血浆中的阿利桑酮。以布鲁塞尔醇为内标。采用Agilent Zorbax Eclipse Plus C-18色谱柱，以水-甲醇为流动相，流速0.2mL/min，梯度洗脱。用多反应监测负电喷雾电离模式的三重四极杆质谱仪分别检测了375.2->；301.1和519.1->；437.4的跃迁。定量下限为5 ng/m L，线性范围为5-2000 ng/m L。日内和日间精密度(RE)分别为-3.6~1.5%和-0.7~4.7%，日内和日间精密度(RSD)分别为2.8~6.7%和3.1~8.0%。该方法已成功地应用于大鼠体内的药物动力学研究。单次静脉给药后消除半衰期(t(1/2))分别为105.5±13.6min、113.3±-39.6min和95.8±23.9min。血药浓度-时间曲线下面积(AUC(0-6h))和初始血药浓度(C-0)与剂量呈线性关系。(C)2014爱思唯尔B.V.保留所有权利。
Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has drawn a lot of attention for its antitumor activity. In this study, a simple and sensitive method for determination of ailanthone in rat plasma was developed for the first time, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Brusatol was used as an internal standard. Separation was achieved on an Agilent Zorbax Eclipse Plus C-18 column with gradient elution using water-methanol as mobile phase at a flow rate of 0.2 mL/min. A triple quadrupole mass spectrometer operating in the negative electrospray ionization mode with multiple reaction monitoring (MRM) was used to detect ailanthone and IS transitions of 375.2 -> 301.1 and 519.1 -> 437.4, respectively. The lower limit of quantification was 5 ng/mL with a linear range of 5-2000 ng/mL. The intra- and inter-day accuracy (RE) ranged from -3.6 to 1.5% and -0.7 to 4.7% and the intra- and inter-day precision (RSD) was between 2.8-6.7% and 3.1-8.0%. The validated method has been successfully applied to a pharmacokinetic study of ailanthone in rats. The elimination half-lives (t(1/2)) were 105.5 +/- 13.6, 113.3 +/- 39.6, and 95.8 +/- 23.9 min after single intravenous administration of 0.5, 1.0, and 1.5 mg/kg ailanthone, respectively. The area under the plasma concentration versus time curve (AUC(0-6 h)) and initial plasma concentration (C-0) were linearly related to dose. (C) 2014 Elsevier B.V. All rights reserved.