非索非那定
化学
普伐他汀
色谱法
瑞舒伐他汀
药理学
蛋白质沉淀
瑞舒伐他汀钙
他汀类
皮塔伐他汀
药代动力学
高效液相色谱法
生物化学
胆固醇
医学
作者
Wei Wu,Rui Cheng,Zhenzhou Jiang,Luyong Zhang,Xin Huang
摘要
A rapid and specific UPLC-MS/MS method with a total run time of 3.5 min was developed for the determination of pravastatin, fexofenadine, rosuvastatin, and methotrexate in rat primary hepatocytes. After protein precipitation with 70% acetonitrile (containing 30% H2 O), these four analytes were separated under gradient conditions with a mobile phase consisting of 0.03% acetic acid (v/v) and methanol at a flow rate of 0.50 mL/min. The linearity, recovery, matrix effect, accuracy, precision, and stability of the method were well validated. We evaluated drug-drug interactions based on these four compounds in freshly suspended hepatocytes. The hepatic uptake of pravastatin, fexofenadine, rosuvastatin, and methotrexate at 4°C was significantly lower than that at 37°C, and the hepatocytes were saturable with increased substrate concentration and culture time, suggesting that the rat primary hepatocyte model was successfully established. Triptolide showed a significant inhibitory effect on the hepatic uptake of these four compounds. In conclusion, this method was successfully employed for the quantification of pravastatin, fexofenadine, rosuvastatin, and methotrexate and was used to verify the rat primary hepatocyte model for Oatp1, Oatp2, Oatp4, and Oat2 transporter studies. Then, we applied this model to explore the effect of triptolide on these four transporters.
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