LC-MS/MS法测定大鼠血浆中齐留通的含量及其药动学研究

An LC-MS/MS method for determining Zileuton in rat plasma and its pharmacokinetic properties

目的:建立测定大鼠血浆中齐留通含量的LC-MS/MS方法,研究齐留通片和齐留通原料在大鼠体内的药动学过程和生物利用度。方法:大鼠灌胃(ig)给药后,分别于不同时间点采血,血浆样品采用LC-MS/MS测定血药浓度,采用DAS 2.0软件求算药动学参数。结果:齐留通的血浆浓度在1~1 000 ng·mL^(-1)范围内线性关系良好(r=0.999 92),日间精密度和日内精密度RSD均小于15%,稳定性、回收率均在85%~115%。齐留通片和齐留通的半衰期分别为6.091和7.91 h,齐留通片在大鼠体内的相对生物利用度为138.90%。结论:该方法可用于测定大鼠血浆中齐留通的含量,齐留通片在大鼠体内吸收较好,本实验结果可为齐留通仿制药的研究提供依据。

Objective： To establish an LC-MS/MS method for determining Zileuton in rat plasma and study the pharmacokinetic properties of Zyflo and Zileuton. Methods： Rats recieved Zyfio and Zileuton by intragastrical administration, plasma samples were extracted at different time. Then the concentrations of Zileuton in plasma were determined. Pharmacokinetic parameters were calculated with DAS 2.0 software. Results： Calibration curve of Zileuton was linear in range of 1 - 1 000 ng·mL^-1（r =0.99992）, RSD of intra- and inter-day were less than 15%. Extraction recoveries and stability were between 85% - 115%. t1/2 of Zyflo and Zileuton were 6. 091 h and 7.91 h, and the relative bioavailability value was 138.90%. Conclusion： The method is successfully applied for determining Zileuton in rat plasma. Zyflo can be obsorbed better in rat, which can be used for the determination o! generic drug study .