苯磺酸氨氯地平片的血药浓度测定及其药动学特征  

Determination of amlodipine in human plasma by LC-MS/MS method and pharmacokinetics of amlodipine besilate tablets in healthy volunteers

作　　者：刘梅[1] 张琰[1] 文爱东[2] 杨林[2] 李微[2] 袁静[2] 高晓华[2] 

机构地区：[1]中国人民解放军第四军医大学唐都医院药学部,西安710038 [2]中国人民解放军第四军医大学西京医院药学部,西安710032

出　　处：《中国临床药学杂志》2007年第4期211-214,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立测定氨氯地平血药浓度的液相色谱-串联质谱分析方法，并用于研究苯磺酸氨氯地平片在健康志愿者体内的药动学特征。方法以乙腈-水-甲酸（80：20：0．5）为流动相，采用大气压化学电离源，选择反应监测方式进行正离子检测。内标物为盐酸苯海拉明，对18名健康志愿者服药后不同时间的氨氯地平血药浓度进行测定。结果氨氯地平的线性范围为0．2．16．0μg·L^-1，定量下限为0．2μg·L^-1。所有血浆分析样品的日内、日间精密度均〈10％，重现性良好。健康受试者口服10mg氨氯地平后的主要药动学参数tmax为（8．2±2．2）h，ρmax为（5．01±2．17）μg·L^-1，t1/2为（48．8±24．2）h，AUC0→1为（196±53．0）μg·h·L^-1，Au0→∞为（243±89．3）μg·h·L^-1。结论本方法选择性强，灵敏度高，能满足氨氯地平制剂的临床药动学研究需要。A/M To establish a fast, sensitive and specific analysis of amlodipine in human plasma and to study pharmacokinetics of amlodipine besilate tablets in healthy volunteers. METHODS Amlodipine was extracted from serum and separated with the mobile phase consisting of acetonitrile-water- formic acid （80： 20： 0.5）. A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Diphenhydramine was used as internal standard. Amlodipine plasma concentrations were analyzed by LC-MS/MS using selected reaction monitoring （SRM） in 18 healthy Chinese male volunteers. RESULTS The standard curve was linear over the range of 0.2 - 16.0 μg· L^-1 of amlodipine in human serum. The limit of quantification was 0.2 μg· L^-1 of serum. The within-day and between-day precision studies showed good reproducibility with coefficients of variation less than 10% for all the analytes. After a single oral dose of 10 mg amlodipine, the following pharrnacokinetic parameters were obtained： tmax Was （8.2 ± 2.2） h, ρmax was （5.01 ± 2.17）μ g· L^-1, t1/2 was （48.8 ± 24.2） h, AUC0→1 was （196±53.0）μg·h·L^-1,AUC0→∞ was （243 ± 89.3）μg·h·L^-1. CONCLUSION The method is sensitive, convenient and proved to be suitable for the clinical investigation of amlodipine pharmacokinetics.

关 键 词：氨氯地平 药动学 液相色谱-串联质谱法 

分 类 号：R96[医药卫生—药理学]