LC-MS/MS法测定血浆中伊拉地平的浓度及其人体药代动力学研究  

Determination of isradipine in human plasma by LC-MS/MS and study on its human pharmacokinetics

作　　者：谢潘潘 薛薇[2,3] 曹国颖[2,3] 胡欣[2,3] 齐文渊[2,3] 史爱欣[2,3] 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]卫生部北京医院药学部,北京100730 [3]药物临床风险与个体化应用评价北京市重点实验室,北京100730

出　　处：《药物分析杂志》2014年第9期1536-1540,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：国家科技部十二五重大新药创制-心脑血管疾病新药临床评价技术平台研究课题(2012ZX09303-008-002)

摘　　要：目的：建立LC-MS/MS法测定人血浆中伊拉地平的浓度,研究中国健康人单剂量口服伊拉地平胶囊后体内药代动力学。方法：采用Waters XterraMS C18色谱柱（2.1 mm×100 mm,3.5μm）,以乙腈-0.5 mmol·L-1醋酸铵水溶液为流动相,梯度洗脱（0-1min,20%乙腈;1-3 min,20%→90%乙腈;3-5 min,90%乙腈;5-5.1 min,90%→20%乙腈;5.1-9 min,20%乙腈）,流速0.3 mL·min-1,柱温40℃;负离子方式检测,扫描方式为多反应监测（MRM）,固相萃取法处理血浆样品;9名受试者单剂量口服10 mg伊拉地平胶囊后,以LC-MS/MS法测定血浆中伊拉地平浓度,使用WinNonlin6.3软件对血药浓度数据进行处理,计算药动学参数。结果：血浆中伊拉地平浓度线性范围为10-10000 pg·mL-1,定量下限为10 pg·mL-1,批内、批间精密度均小于15%。单剂量口服10 mg伊拉地平胶囊后主要的药动学参数Cmax为（4610.21±147.91）pg·mL-1,Tmax为（1.46±0.42）h,t1/2为（11.65±4.38）h,AUC0-t（34466±11140）pg·h·mL-1。结论：本文建立的LC-MS/MS法符合方法学考察要求,适合于伊拉地平胶囊在中国健康受试者体内药代动力学研究。Objective：To develop an LCMS /MS method for quantification of isradipine in human plasma and study the in vivopharmacokinetics after administration of isradipine capsules at a single dose to healthy Chinese volunteers. Method：The isradipine concentrations were determined by LCMS /MS using a Waters XterraMS C18column（ 2. 1 mm × 100 mm,3. 5 μm） with a mobile phase of acetonitrilewater（ containing 0. 5 mmol·mL1ammonium acetate） by gradient elution（ 01 min,20% acetonitrile; 13 min,20% →90% acetonitrile; 35 min,90% acetonitrile; 55. 1 min,90% →20% acetonitrile; 5. 19 min,20% acetonitrile） at a flow rate of 0. 3 mL·min1; the column temperature was 40 ℃ under negative ionization（ MRM） mode. Plasma samples were processed by solid phase extraction. After oral administration of isradipine capsules at a single dose to 9 healthy volunteers,the plasma concentrations of isradipine were determined by LCMS /MS method. The plasma concentrations were determined and the pharmacokinetic parameters were calculated by WinNonlin6. 3. Results：The calibration curve was linear within the range of 1010000 pg·mL1. The LLOQ was 10 pg·mL1and RSDs of intraand interday were less than 15%. The pharmacokinetic parameters after administration of 10 mg isradipine capsules at a single dose were as follows：Cmaxwas（ 4610. 21 ± 147. 91） pg·mL1; Tmaxwas（ 1. 46 ± 0. 42） h; t1 /2was（ 11. 65 ± 4. 38） h;AUC0twas（ 34466 ± 11140） pg·h·mL1. Conclusion：The developed LCMS /MS method met the requirements of methodology verification and was suitable for the pharmacokinetic study of isradipine in healthy Chinese volunteers.

关 键 词：伊拉地平 液相色谱-串联质谱 血药浓度 药代动力学 固相萃取 人血浆样品 临床用药监测 

分 类 号：R917[医药卫生—药物分析学]