化学
色谱法
生物利用度
药代动力学
电喷雾电离
甲酸
选择性反应监测
同位素稀释
稀释
质谱法
串联质谱法
分析化学(期刊)
药理学
医学
热力学
物理
作者
Jinglai Li,Sha Liao,Xiaoying Wang,Qian Liu,Fei Meng,Wenpeng Zhang,Tianhong Zhang,Cui-Ping Yang,Xinyi Song,Huan Luo,Juan Wang,Zheng Li,Bo-Hua Zhong,Zhenqing Zhang
摘要
A rapid, specific and high-throughput stable isotope-dilution LC-MS/MS method was developed and validated with high sensitivity for the quantification of R-phencynonate (a eutomer of phencynonate racemate) in rat and dog plasma. Plasma samples were deproteinized using acetonitrile and then separated on a C8 column with an isocratic mobile phase containing acetonitrile-water-formic acid mixture (60:40:0.1, v/v/v) at a flow rate of 0.2 mL/min. Each sample had a total run time of 3 min. Quantification was performed using triple quadrupole mass spectrometry in selected reaction monitoring mode with positive electrospray ionization. The method was shown to be highly linear (r2 > 0.99) and to have a wide dynamic range (0.1-100 ng/mL) with favourable accuracy and precision. No matrix effects were observed. The detailed pharmacokinetic profiles of R-phencynonate at therapeutic doses in rats and dogs were characterized by rapid oral absorption, quick clearance, high volume of distribution and poor absolute bioavailability. R-Phencynonate lacked dose proportionality over the oral dose range, based on the power model. However, the area under concentration-time curve and the maximum plasma concentration increased linearly in a dose-dependent manner in both animal models. The absolute bioavailability of R-phencynonate was 16.6 ± 2.75 and 4.78 ± 1.26% in dogs and rats, respectively.
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