高效液相色谱法测定乙吗噻嗪在人的血浆浓度及药代动力学

建立了反相高效液相色谱法测定人血浆中乙吗噻嗪浓度。色谱柱采用SpherisotbC18柱(25cm×4.6mm,5μm),流动相为甲醇—水—三乙胺(70:30:0.4,pH6.5),检测波长268nm。用乙腈沉淀蛋白后,吹干浓缩进样。血药浓度在20～4000ng/ml范围内呈线性关系,相关系数0.9994,血浆最低检测浓度3ng/ml。方法回收率90～103%,日内、日间RSD2.4～10.2%。应用该法研究了8名志愿者口服乙吗噻嗪片后的药代动力学,用一室模型拟合,消除相半衰期为1.75±0.45h。本法简便、回收率和灵敏度高、重复性好,适于临床药代动力学和药效学的研究。

DETERMINATION OF ETHMOZINE IN HUMAN PLASMA BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY AND ITS PHARMAC0KINETICS

Following detailed study,a rapid and sensitive assay for ethmozine in humanplasma has been developed using reversed phase high performance liquid chromatography(HPLC).Plasma samples were prepared for analysis by addition of internal standard(5-chloro-2-amino-benzophenone )followed by protein preci pitation using acetonitrile.A nalytical column was a C 18 spherisorb.The mobile phase consisted of mathanol—water—triethylamine(70 :30:0.4,v/v/v,pH6.5).The column effluent was monitored at 268 nm. The calibration curve was linear in the rangefrom 20 ng/ml to 4000 ng/ml with r=0. 9994.The detection limit of this method was 3 ng/ml.Themethed showed good precision and the analytical recovery of ethmozine from plasma was 90～105%;The relative standard deviations for within- day and between- day were 2.4～6;3%and 4.5～10.2%respectively.The plasma drug concentration- time course in man after oral administration of 400 mgafter conformed to a 1-compartment open model with a first order absorption phase.Mean T1/2valuewas 1.75+0.45h.