单剂量静注新型钙离子增敏剂M6在大鼠血浆中的药代动力学分析

发布时间：2018-07-17 21:26

【摘要】：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。
[Abstract]:Aim: to investigate the pharmacokinetic characteristics of a new calcium sensitizer M6 in rat plasma and to establish a rapid and simple HPLC method for the determination of M6 in rat plasma. Methods: by using jugular vein blood sampling method, the changes of blood drug concentration in rats were studied after injection of M6 into caudal vein at 1: 3, 5, 10, 15, 30 min and 1, 2, 2, 4, 4, 6, 6 hours after injection, and the plasma concentrations were determined by HPLC. The mobile phase consisted of 1% acetic acid aqueous solution and acetonitrile (85:15). The detection wavelength was 280 nm. The plasma concentration and time curves were plotted. The pharmacokinetic parameters of M6 were calculated by PKSolver data processing software. Results the linear range was 3.125 渭 g / L ~ (-1) and the lowest quantitative limit was 0.6 mg / L ~ (-1). The main pharmacokinetic parameters of the method were: peak time (tmax) 1 min, maximum blood concentration 6.67 mg L ~ (-1), half-life (t _ (1 / 2) 21.36 min, mean retention time (MRT) 30.83 min, maximum plasma concentration (C max) 6.67 mg L ~ (-1), half life (t _ (1 / 2) 21.36 min, mean retention time (MRT) 30.83 min. There is a double peak phenomenon. Conclusion the t _ (1 / 2) of M6 is longer than that of PPTA and has the characteristic of prolonging the metabolic time. It is expected to develop a new M6 drug. The established HPLC is sensitive, rapid and accurate. It can be used to determine the mass concentration of M 6 in rat plasma.
【作者单位】：南方医科大学;广州军区总医院;广州市众为生物技术有限公司;广东药学院;
【基金】：广东省教育部产学研结合项目(2012B091100170) 广东省重大科技专项(2012A080204010) 广州市创新平台建设与共享-重点实验室项目(201509010012) 国家“重大新药创制”科技重大专项(2011ZX091011-003)
【分类号】：R965

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