人血浆中阿戈美拉汀的浓度测定及其药动学研究  

Concentration determination of agomelatine in human plasma and its pharmacokinetics study

作　　者：程捷[1] 贺娟 茅晓寅 周沁逸 张梦琪[1] 张慧[2] CHENG Jie;HE Juan;MAO XiaoYin;ZHOU QinYi;ZHANG MengQi;ZHANG Hui(Institution for Drug Clinical Trials,Shanghai Xuhui Central Hospital,Shanghai 200031,China;Department of Pharmacy,Community Health Service Center of Xietu Street,Xuhui District of Shanghai,Shanghai 200032,China)

机构地区：[1]上海市徐汇区中心医院药物临床试验机构,上海200031 [2]上海市徐汇区斜土街道社区卫生服务中心药剂科,上海200032

出　　处：《药学服务与研究》2018年第3期199-202,共4页Pharmaceutical Care and Research

摘　　要：目的:建立LC-MS/MS法测定阿戈美拉汀在人血浆中的浓度,并测定其在健康志愿者体内的药动学参数。方法:以ACQUITY UPLC BEH C18柱(50mm×2.1mm,1.7μm)为分析柱,50mmol/L甲酸铵-甲酸-水(0.75∶1.25∶98)溶液(A)-乙腈(B)为流动相,梯度洗脱(0~0.65min,43%B相;0.65~0.66min,43%~90%B相;0.66~1.00min,90%B相;1.00~1.10min,90%~43%B相,1.10~2.50min,43%B相)。采用电喷雾离子源,多离子反应监测(MRM)正离子扫描分析。阿戈美拉汀和内标阿戈美拉汀-氘6离子对分别为m/z244.1→185.1和m/z250.1→188.1。测定48名健康志愿者单剂量口服阿戈美拉汀25mg后的血药浓度和药动学参数。结果:在0.05~10.00ng/ml浓度范围内,阿戈美拉汀具有良好的线性关系。日内、日间精密度RSD均<6%,平均提取回收率在77.28%~83.67%(n=6)。单次口服给药后,阿戈美拉汀的cmax为(16.16±31.52)ng/ml,AUC0~∞为(17.05±21.17)ng·h·ml^(-1),AUC0~12h为(16.95±21.11)ng·h·ml^(-1),tmax为(1.20±0.88)h,t1/2为(0.96±0.33)h。结论:本方法简便、灵敏、精确,重现性好,可用于人血浆中阿戈美拉汀浓度的测定及药动学研究。Objective：To establish a LC-MS/MS method for concentration determination of agomelatine in human plasma and to determine its pharmacokinetics parameters in healthy volunteers.Methods：ACQUITY UPLC BEH C_（18）（50 mm×2.1 mm,1.7μm）was used with the mobile phase consisting of 50 mmol/L ammonium formate-formic acid-water（0.75∶1.25∶98,phase A）and acetonitrile（phase B）at a gradient elution（0-0.65 min 43% B,0.65-0.66 min 43%-90% B,0.66-1.00 min 90% B,1.00-1.10 min 90%-43% B,1.10-2.50 min 43% B）.Mass spectrometry was performed using electro spray ionization（ESI）,combined with positive ion scanning switch.The mass transition pairs of m/z244.1→185.1 and m/z250.1→188.1 were agomelatine and internal standard[~2H_6]-agomelatine.The plasma concentrations and pharmacokinetics parameters were determined after administration of a single oral dose of 25 mg agomelatine in 48 healthy volunteers.Results：In the concentration ranges of 0.05-10.00 ng/ml,agomelatine displayed good linearity.The intra-and inter-day precisions（RSD）were less than 6%.The average recovery rate was 77.28%-83.67%（n=6）.The main pharmacokinetics parameters after a single oral dose of agomelatine were as follows：cmax（16.16±31.52）ng/ml,AUC_（0-∞）（17.05±21.17）ng·h·ml^（-1）,AUC0-12 h（16.95±21.11）ng·h·ml^（-1）,tmax（1.20±0.88）h,and t1/2（0.96±0.33）h.Conclusion：The established method was convenient,sensitive,accurate and reproducible,and it could be used for concentration determination of agomelatine in human plasma and the study of pharmacokinetics.

关 键 词：阿戈美拉汀 血药浓度 药代动力学 色谱法 高效液相 质谱法 联用 

分 类 号：R969[医药卫生—药理学] R971.43[医药卫生—药学]