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  

Pharmacokinetic Analysis of New Calcium Sensitizer of M6 in Rat Plasma by Single Intravenous

作　　者：樊鸿浩 邓乐君[1,2] 朱晋辉 李健[2] 万华印 李伟达[4] 招健华 李茹冰[1,2] 

机构地区：[1]南方医科大学,广州510515 [2]广州军区总医院,广州510010 [3]广州市众为生物技术有限公司,广州510663 [4]广东药学院,广州510006

出　　处：《中国实验方剂学杂志》2015年第23期83-86,共4页Chinese Journal of Experimental Traditional Medical Formulae

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)

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。Objective： To explore pharmacokinetic characteristics of the new calcium sensitizer-M6 in rat plasma,and establish a fast,convenient and effective HPLC for determination of M6 in rat plasma. Method：Jugular vein haemospasia was adopted,M6 was injected by tail vein in rats,plasma concentration was determined by HPLC after 1,3,5,10,15,30 min and 1,2,4,6,8 h, mobile phase of 1% acetic acid solutionacetonitrile（ 85∶ 15）,detection wavelength was set at 280 nm. Plasma concentration-time curve was drawn,and pharmacokinetic parameters were calculated by PKSolover software. Result： Linear range of M6 was 3. 125-200mg·L^-1,the limit of quantitation was 0. 6 mg·L^-1,the intra-day,inter-day precision and stabilization were less than 10%, recovery of method was more than 85%. These main pharmacokinetic parameters of M6 were as followed： tmaxof 1 min,Cmaxof 6. 67 mg·L^-1,t1/2 of 21. 36 min,MRT of 30. 83 min,concentration-time curve showed double peaks. Conclusion： Results suggest that t1/2 of M6 is longer than t1/2 of its prototype drug-PPTA.This HPLC is sensitive,rapid and accurate,it can be empolyed to determine concentration of M6 in rat plasma.

关 键 词：钙离子增敏剂 M6 盐酸椒苯酮胺 颈静脉抽血法 药物代谢动力学 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]