人血浆中单硝酸异山梨酯的LC-MS/MS法测定及其药动学

Determination of Isosorbide 5-Mononitrate in Human Plasma by LC-MS/MS and Its Pharmacokinetics

建立了液相色谱-串联质谱法测定人血浆中的单硝酸异山梨酯。采用Venusil ASB C8色谱柱,以甲醇-5 mmol/L乙酸铵溶液(60︰40)为流动相,电喷雾离子源,负离子模式,多反应监测(MRM)。监测离子为m/z 249.9→58.2(单硝酸异山梨酯)和m/z 149.9→106.4(内标,对乙酰氨基酚)。单硝酸异山梨酯在5～1 000 ng/ml范围内线性关系良好,低、中、高浓度组的提取回收率分别为69.6%、58.9%和64.6%。志愿者单剂量口服20 mg单硝酸异山梨酯口崩片后的主要药动学参数为:cmax(343.0±87.3)ng/ml,tmax(1.11±0.67)h,t1/2(6.01±1.29)h,AUC0→t(2 578±605)ng.h.ml-1,AUC0→∞(2 785±653)ng.h.ml-1。

A LC-MS/MS method was established for the determination of isosorbide 5-mononitrate in human plasma.The sample was separated on a Venusil ASB C8 column with the mobile phase of methanol-5 mmol/L ammonium acetate solution（60︰40）.The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring（MRM） mode via electrospray ionization（ESI） source in negative ion mode.The transitions of m/z 249.9→58.2（isosorbide 5-mononitrate） and m/z 149.9→106.4（internal standard,paracetamol） were used.The calibration curve was linear in the concentration range of 5-1 000 ng/ml.The extraction recoveries of low-,middle-and high-concentration groups were 69.6%,58.9% and 64.6%,respectively.After administration of 20 mg isosorbide 5-mononitrate orally disintegrating tablets to volunteers,the main pharmacokinetic parameters were as follows： cmax（343.0±87.3） ng/ml,tmax（1.11±0.67） h,t1/2（6.01±1.29） h,AUC0→t（2 578±605） ng·h·ml-1,AUC0→∞（2 785± 653） ng·h·ml-1.