岩黄连总碱胶囊在健康受试者体内的药动学研究  

Pharmacokinetics of Yanhuanglian total alkaloids capsules in healthy volunteers

作　　者：戴国梁[1] 欧阳冰琛 王一清[1] 陈闪闪 杨欣怡 许美娟[1] 居文政[1] 刁和芳 DAI Guo-liang;OUYANG Bing-chen;WANG Yi-qing;CHEN Shan-shan;YANG Xin-yi;XU Mei-juan;JU Wen-zheng;DIAO He-fang(Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Nanjing 210029,China;Jiangsu Hongdian Research Institute of Traditional Chinese Medicine Industry Co.Ltd.,Jiangsu Nanjing 210042,China)

机构地区：[1]南京中医药大学附属医院临床药理科,江苏南京210029 [2]江苏弘典中药产业研究院有限公司,江苏南京210042

出　　处：《中国医院药学杂志》2022年第7期702-706,共5页Chinese Journal of Hospital Pharmacy

基　　金：江苏省中医药领军人才(编号:SLJ0208);江苏省自然科学基金面上项目(编号:BK20181504,BK20211394)。

摘　　要：目的:建立LC-MS/MS法测定人血浆中脱氢卡维丁的浓度,研究不同剂量岩黄连总碱胶囊在中国健康受试者多次给药后的药动学。方法:采用随机、开放、多剂量给药设计的方法。16名健康志愿者随机分为2个剂量组(2400 mg和3200 mg),男女各半,每组8例,分别多次口服岩黄连总碱胶囊,每日1次,连续7 d,第7天在给药前及给药后不同时间点采取血样本。血浆样品以乙腈沉淀蛋白,色谱柱为Agilent ZORBAX SB-C_(18)(3.0 mm×100 mm,3.5μm),流动相为0.2%甲酸水溶液(含1 mmol·L^(-1)甲酸铵)∶乙腈(30∶70,V/V),ESI离子源,正离子扫描,MRM检测模式。检测离子:m/z 350.3→334.3(脱氢卡维丁);m/z 272.2→171.3(右美沙芬)。利用WinNonlin 8.0软件计算药动学参数。结果:脱氢卡维丁线性范围为0.015~3 ng·mL^(-1),定量下限为0.015 ng·mL^(-1),方法学的各项指标均符合要求。2个剂量组(2400 mg和3200 mg)多次给药后的主要药动学参数分别为t_(max):(1.75±1.04),(2.06±0.98)h;t_(1/2):(31.59±17.32),(35.98±14.46)h;AUC_(0-t):(2.637±0.504),(3.150±0.485)ng·h·mL^(-1);AUC_(0-∞):(5.512±1.792),(7.649±3.306)ng·h·mL^(-1)。结论:本研究建立的LC-MS/MS测定法简便、灵敏,可用于岩黄连总碱胶囊的人体药动学研究。OBJECTIVE To develop the LC-MS/MS method for the determination of dehydrocavidine in human plasma,and study pharmacokinetics of Yanhuanglian total alkaloids capsules at different doses with repeated oral administration in Chinese healthy volunteers.METHODS A randomized,open,multi-dose design was conducted.Sixteen healthy volunteers(with half males and half females)were randomized into two groups with eight cases in each(2400 mg and 3200 mg).The sixteen subjects were orally administrated with Yanhuanglian total alkaloids capsules,once a day for seven days.On the 7^(th) day,the blood samples were collected at different time points after administration.The separation of plasma was performed on an Agilent ZORBAX SB-C_(18) column(3.0 mm×100 mm,3.5μm)after precipitated by acetonitrile with the mobile phase consisting of 0.2%formic acid(containing 1 mmol·L^(-1) ammonium formate)-acetonitrile(30∶70,V/V).Dehydrocavidine and dextromethorphan(IS)were detected by the MS system with an electrospray ionization(ESI)interface in positive ion mode.Multiple reaction monitoring(MRM)was used to monitor precursor to product ion transition of m/z 350.3→334.3 for dehydrocavidine and m/z 272.2→171.3 for IS.Pharmacokinetic parameters were calculated by WinNonlin 8.0 software.RESULTS The linear range of dehydrocavidine was 0.015-3 ng·mL^(-1).The lower limit of quantification was 0.015 ng·mL^(-1).The indicators of method validation were in line with the requirements.The main pharmacokinetic parameters of dehydrocavidine after oral administration of multiple doses of 2400 mg and 3200 mg were as follows,t_(max) were(1.75±1.04)h and(2.06±0.98)h,t_(1/2) were(31.59±17.32)h and(35.98±14.46)h,AUC_(0-t) were(2.637±0.504)ng·h·mL^(-1) and(3.150±0.485)ng·h·mL^(-1),AUC_(0-∞)were(5.512±1.792)ng·h·mL^(-1) and(7.649±3.306)ng·h·mL^(-1),respectively.CONCLUSION The LC-MS/MS method is simple and sensitive,and can be successfully applied to the pharmacokinetic study of Yanhuanglian total alkaloids capsules in healthy Chinese volun

关 键 词：岩黄连总碱胶囊 脱氢卡维丁 人体 药动学 高效液相串联质谱 

分 类 号：R284.1[医药卫生—中药学]