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目的:探究新型钙离子增敏剂M6在大鼠血浆中的药代动力学特点,建立快速、简便的检测大鼠血浆中M6血药浓度的高效液相色谱法(HPLC)。方法:采用颈静脉抽血法,考察大鼠尾静脉注射M6后于1,3,5,10,15,30 min和1,2,4,6,8 h的血药浓度变化,采用HPLC测定血药浓度,流动相1%乙酸水溶液-乙腈(85∶15),检测波长280 nm,绘制血药浓度-时间曲线,通过PKSolver数据处理软件计算M6药代动力学参数。结果:M6检测的线性范围3.125~200 mg·L~(-1),最低定量限0.6 mg·L~(-1),日内、日间精确度和稳定性试验的RSD均<10%,方法回收率均>85%。M6在大鼠体内的主要药代动力学参数为达峰时间(tmax)1 min,最大血药浓度(Cmax)6.67 mg·L~(-1),半衰期(t_(1/2))21.36 min,平均滞留时间(MRT)30.83 min;药-时曲线出现了双峰现象。结论:M6的t_(1/2)较原型药物PPTA延长,具有代谢时间延长的特点,有望开发M6的新药物。建立的HPLC灵敏、快速、准确,可用于大鼠血浆中M6质量浓度的测定。
AIM: To investigate the pharmacokinetics of a novel calcium-sensitizer M6 in rat plasma and to establish a rapid and simple HPLC method for the determination of M6 in rat plasma. Methods: The jugular vein blood was drawn to study the change of plasma concentration at 1, 3, 5, 10, 15, 30 min and 1, 2, 4, 6 and 8 h after tail vein injection of M6 in rats. The plasma concentration, mobile phase 1% acetic acid aqueous solution-acetonitrile (85:15) and detection wavelength 280 nm were used to draw the plasma concentration-time curve. The pharmacokinetic parameters of M6 were calculated by PKSolver data processing software. Results: The linear range of M6 was 3.125 ~ 200 mg · L -1, the lowest limit of quantitation was 0.6 mg · L -1. The RSD of intra-day and inter-day accuracy and stability test were all less than 10% Recovery rates were> 85%. The main pharmacokinetic parameters of M6 in rats were: peak time (tmax) 1 min, maximum plasma concentration (Cmax) 6.67 mg · L -1, half life (t 1/2) 21.36 min , Mean retention time (MRT) was 30.83 min; bimodal phenomenon appeared on the drug-time curve. Conclusion: The t_ (1/2) of M6 is longer than that of the prototypical drug PPTA and has the characteristic of prolonging the metabolism time. It is expected to develop a new drug of M6. The established HPLC is sensitive, rapid and accurate and can be used for the determination of M6 mass concentration in rat plasma.