LC-MS/MS法测定阿戈美拉汀人体血浆中的浓度及两种片剂的生物等效性研究  

Study on the Determination of Concentration and Bioequivalence of 2 kinds of Agomelatine Preparations in Human Plasma by LC-MS/MS

作　　者：邵凤[1,2] 杨欣怡[1,2] 吴锡凤 徐怀友[1,2] 朱玲玲 路于 陶春蕾[1,2] 

机构地区：[1]安徽中医药大学研究生院,合肥230031 [2]安徽万邦医药科技有限公司,合肥230031

出　　处：《中国药房》2015年第17期2342-2345,共4页China Pharmacy

摘　　要：目的：建立一种快速、准确测定人血浆中阿戈美拉汀浓度的方法,并研究两种片剂的生物等效性。方法：120名男性健康志愿者随机分成两组,采用两制剂四周期重复双交叉试验设计,先后两次口服阿戈美拉汀片受试制剂与参比制剂25 mg后采用液相色谱-串联质谱（LC-MS/MS）法测定阿戈美拉汀人体血浆中的浓度。以地西泮作为内标,色谱柱为Phenomenex Luna C18,流动相为甲醇-0.1%甲酸（80∶20）。采用正离子检测方式,以多反应监测,用于定量的离子分别为阿戈美拉汀m/z 244.0→185.0,地西泮m/z 285.1→154.0,用DAS 3.2.5软件进行数据处理。结果：阿戈美拉汀血药浓度在0-05-20 ng/ml范围内线性关系良好。受试制剂与参比制剂的主要药动学参数：cmax分别为（12-032±12.190）、（0.891±11-035）ng/ml,tmax分别为（0.658±0.492）、（0.709±0.465）h,t1/2分别为（0.813±0.356）、（0.960±0.849）h,AUC0-12 h分别为（12.637±12.852）、（11.572±10.348）ng·h/ml、AUC0-∞分别为（12.770±12.871）、（11.734±10.369）ng·h/ml。方差分析表明两制剂的主要药动学参数之间差异均无统计学意义（P〉0-05）,双单侧t检验结果表明两制剂为生物等效制剂。结论：LC-MS/MS法能够快速、准确地测定阿戈美拉汀在人体血浆中的浓度,两种片剂生物等效。OBJECTIVE： To establish a fast and accurate method for determining the concentration of agomelatine in human plasma and study the bioequivalence. METHODS： 60 healthy male vohmteers were randomly divided into 2 groups. It included two prescriptions, four-cycle, repeat and two-cross-over trails. The concentration of agomelatine in human plasma was determined by LC-MS/MS after orally giving test and reference preparations. With the internal standard of diazepam, the column was Phenomenex Luna-C18 with the mobile phase of methanol-formic acid （80：20）. API-3000 positive ionization mode was conducted in MRM mode, monitoring the transitions agomelatine m/z 244.0±185.0,Diazepatm m/z 285.1±154.0 , and DAS 3.2.5 was used to analyze the data. RESULTS： The linear range of the plasma concentration of agomelatine was 0,05-20 ng/ml. The main pharmacokinetic parameter cm2 of test and reference preparations was respectively （12-032 ± 12.190）（0.891± 11-035）ng/ml, tmax was respectively（0.658± 0.492） （0.709± 0.465）h, tl/2 was respectivel （0.813 ± 0.356） （0.960 ± 0.849）h, AUC0-,2 h was respectively （12.637 ± 12.852） （11.572 ±10.348） ng· h/ml. and AUC0- was respectively （ 12.770±12.871） （ 11.734 ±10.369） ng- h/ml, Analysis of variance showed there were no significant difference in the pharmacokinetic parameters of 2 preparations and the results of double-sided t test showed the 2 preparations were bioequivalent preparations. CONCLUSIONS： LC-MS/MS can monitor the concentration of agomelatine in human plasma accurately and rapidly. The 2 preparations have bioequivalence.

关 键 词：液相色谱-串联质谱法 阿戈美拉汀 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]