5-单硝酸异山梨酯血药浓度测定及其在人的药代动力学

采用气相色谱-电子捕获检测法测定 5-单硝酸异山梨酯的血药浓度。样品经乙醚—正己烷混合溶剂提取,三氟醋酐进行衍生化后,用5% SE-30硅烷化玻璃填充柱分离,以硝酸异山梨酯为内标,⁶³Ni电子捕获检测器检测。此法操作简便,日内、日间误差分别小于4%和6.5%,平均回收率为99.62%±1.19%。在20～800ng·mL^-1血浆浓度范围内呈线性关系(γ=0.9995)。最低检测浓度为2.0ng·mL^-1。应用此法研究了10名健康志愿者单次口服20mg 5-单硝酸异山梨酯片后的药代动力学。

DETERMINATION OF ISOSORBIDE-5-MONONITRATE IN PLASMA BY GC-ECD AND STUDY ON ITS PHARMACOKINETICS IN TEN VOLUNTEERS

A rapid, accurate and sensitive gas chromatographic method was developed for the determination of isosorbide-5-mononitrate(5-ISMN) in 0.5 ml plasma. The instrument was equipped with 5% SE-30 glass packed column (2 m x 3 mm) and electron-capture detector. Isosorbide dinitrate (ISDN) was used as internal standard. The plasma was extracted with a mixture of ethyl ether and n-hexane (4:1) to give mean recoveries of 100.1% of 5-ISMN. The extracts reacted with trifluoroacetic anhydride and the derivatives were analyzed. The calibration curves were linear over a wide range of concentrations (20-800 ng.ml-1), and the detection limit of 5-ISMN was 2.0 ng.ml-1. The precisions (RSD%, n = 5) of within-day and day-to-day were less than 4% and 6.5%, respectively. The pharmacokinetic characteristics of 5-ISMN in ten human volunteers after a single oral dose of 20 mg 5-ISMN were investigated. The concentration-time curve was fitted to a one-compartment model.