人血浆中单硝酸异山梨酯的LC-MS/MS法测定及其药动学

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U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,AUC0-0→t(2 578±605) ng·h·ml-1,AUC0→∞(2 785±653) ng·h·ml-1.

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

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.