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.
作者
程捷
贺娟
茅晓寅
周沁逸
张梦琪
张慧
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)
出处
《药学服务与研究》
CAS
2018年第3期199-202,共4页
Pharmaceutical Care and Research
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
agomelatine
blood concentration
pharmacokinetics
chromatography
high performance liquid
massspeetrometry
tandem
