人血浆中非索非那定的LC-MS/MS法测定及药动学

Determination of Fexofenadine in Human Plasma by LC-MS/MS and Its Pharmacokinetics

建立了LC-MS/MS法测定人血浆中的非索非那定浓度。以格列美脲为内标,采用C18柱,流动相为甲醇-水(含15mmol/L乙酸铵和0.05%甲酸)(68︰32),电喷雾离子化源,选择性正离子反应监测,检测离子为m/z502.1→466.2(非索非那定),m/z491.2→352.0(格列美脲),并用于人体药动学研究。20名健康志愿者单剂量口服非索伪麻缓释胶囊(非索非那定60、120mg)后非索非那定的主要药动学参数为:t1/2β(11.34±4.59)和(11.09±3.27)h,tmax(4.20±0.98)和(3.72±1.21)h,cmax(159.28±76.81)和(368.89±165.21)ng/ml,AUC0-48h(997.87±421.12)和(2386.3±867.5)ng·h·ml-1;多剂量口服非索伪麻缓释胶囊(60mg,bid)后非索非那定的主要药动学参数为:cmin(35.45±21.56)ng/ml,cav(97.88±57.12)ng/ml,DF(1.78±0.32),AUCss(1196.26±665.06)ng·h·ml-1。

A LC-MS/MS method was established for the determination of fexofenadine in human plasma.Glimepiride was used as internal standard.A C18 column was used,with the mobile phase of methanol-water（containing 15 mmol/L ammonium acetate and 0.05% formic acid）（68：32）.ESI was applied and operated in positive ion selective reaction monitoring mode.The detected ions were m/z 502.1→466.2（fexofenadine）,m/z 491.2→352.0（glimepiride）.The pharmacokinetics of single oral dose and multiple oral dose of fexofenadine/pseudoephedrine sustained-release capsules in 20 healthy volunteers was investigated.For single dosage（60 and 120 mg fexofenadine）,the main pharmacokinetic parameters of fexofenadine were as follows：t1/2β（11.34±4.59） and（11.09±3.27） h,tmax（4.20±0.98） and（3.72±1.21） h,cmax（159.28±76.81） and（368.89±165.21） ng·ml-1,AUC0-48h（997.87±421.12） and（2 386.3± 867.5） ng·h·ml-1.For multiple dosage（60 mg fexofenadine,bid）,the main pharmacokinetic parameters of fexofenadine were as follows：cmin（35.45±21.56） ng/ml,cav（97.88±57.12） ng/ml,DF（1.78±0.32）,AUCss（1 196.26±665.06） ng·h·ml-1.