LC-MS/MS法研究阿托伐他汀钙对大鼠体内丁苯酞药代动力学影响  

Effect of Atorvastatin Calcium in vivo Pharmacokinetics ofButyphthalide in Rats by HPLC-MS/MS Method

作　　者：贺少龙 文恩辉 费平霞[1] 党宏万[1,2] 魏世杰[1,2] He Shaolong;Wen Enhui;Fei Pingxia;Dang Hongwan;Wei Shijie(Department of Pharmacy,General Hospital of Ningxia Medical University,Yinchuan 750000,China;Department of Clinical Pharmacology,General Hospital of Ningxia Medical University,Yinchuan 750000,China;The First Affiliated Hospital of Xi’an Medical University,Xi’an 710077,China)

机构地区：[1]宁夏医科大学总医院药剂科,宁夏银川750000 [2]宁夏医科大学总医院临床药理研究室,宁夏银川750000 [3]西安医学院第一附属医院,陕西西安710077

出　　处：《山东化工》2023年第12期102-104,107,共4页Shandong Chemical Industry

基　　金：宁夏医科大学校级科研项目(XM2021074);宁夏药物创制与仿制药研究重点实验室项目(宁科计字[2017]36号);宁夏回族自治区重点研发项目(2021BEG03102)。

摘　　要：目的:建立LC-MS/MS法测定大鼠血浆中丁苯酞血药浓度,研究阿托伐他汀钙对其丁苯酞药代动力学的影响。方法:采用随机平行对照实验设计,将14只SD大鼠随机分为两组,单次灌胃给药,A组给药量70 mg·kg^(-1)丁苯酞和等体积0.9%NaCl(代替阿托伐他汀钙给药体积),B组给药量70 mg·kg^(-1)丁苯酞和8 mg·kg^(-1)阿托伐他汀钙。用LC-MS/MS法测定不同时间点大鼠血浆样本中丁苯酞药物浓度,通过DAS 2.0软件计算药代动力学参数。结果:丁苯酞在5~1000 ng·mL^(-1)内与峰面积线性关系良好,提取回收率在62%~79%,日内及日间RSD均小于15%,稳定性考察结果良好。丁苯酞单独给药和与阿托伐他汀钙联用的药代动力学参数无显著差异。结论:该方法简单高效、灵敏,可用于临床研究。阿托伐他汀钙对丁苯酞的药代动力学过程无明显影响。Objective:To establish an HPLC-MS/MS method for determining the concentration of butylphthalide(NBP)and investigate the effect of atorvastatin calcium(ATV)in vivo pharmacokinetics in rats.Methods:14 Sprague-Dawley(SD)rats were randomly divided into two group which was designed as a randomized parallel control trial.The 70 mg·kg^(-1) NBP was administrated to rats in A group(0.9%NaCl)and B group(8 mg·kg^(-1) ATV).The plasma concentration of NBPt was determined by HPLC-MS/MS.DAS2.0 was used to assess the pharmacokinetic parameter of NBP.Results:The linearity of NBP was 5~1000 ng·mL^(-1).The inter-day and intra-day RSD were all lower than 15%,and the method recoveries were at 62%~79%,with good stability.There was no significant difference in pharmacokinetic parameters between NBP administration alone and co-administration with ATV.Conclusion:The method was fast,simple,accurate and sensitive,which is suitable for clinical study.There was no no significant effect on the pharmacokinetic process between ATV and NBP.

关 键 词：LC-MS/MS 丁苯酞 阿托伐他汀钙 药代动力学 

分 类 号：TQ460[化学工程—制药化工]