文拉法辛的人体药代动力学

目的建立HPLC-荧光法测定人血浆中文拉法辛浓度，研究其在中国健康人体内的药代动力学。方法以Diamonsil C18（150mm×4．6mm，5um）为色谱柱；流动相为乙腈-磷酸盐缓冲液（pH3．0）．三乙胺（33．5：66．5：1，V/V／V）；流速1．0ml／min；进样量：20．0ul，内标为马普替林。血浆样品经正己烷．异戊醇提取，荧光检测条件：λex276nm，λem596nm。结果文拉法辛在10．0—800．0ng·ml^-1浓度范围内线性关系良好（r=0．9999），最低血药检测浓度为16．99ng·ml^-1。文拉法辛浓度30．0，150．0，600．0ng·ml^-1的萃取回收率和相对回收率分别在81．51％-91．08％、98．7％-112．6％范围内，日内和日间精密度的RSD分别小于12％和10％（n=5）。文拉法辛的主要药动学参数：t1／2（6．57±2．81）h，Tmax（3．11±0．93）h，Cmax（273．38±75．44）ng·ml^-1，AUC（0-1）（2237．54±816．67）ng·h·ml^-1，AUC（0-∞）（2456．13±838．30）ng·h·ml^-1。结论HPLC-荧光法灵敏、准确、重复性好，适合于文拉法辛的临床药动学研究。

Pharmacokinetics of Venlafaxine

Aim To establish a method to determine the concentration of venlafaxine in human plasma using High performance Liquid Chromatography-Fluoresence （HPLC-F）. Methods The analytical column was Diamonsil C18 （150mm × 4.6mm,5 um） ;the mobile phase was acetonitrile-phosphate buffer solution（pH 3.0）-triethylamine （33.5： 66.5：1 ,V/V/V） ;the flow rate was 1.0ml/min;and the injection volume was 20 td,and the internal stand- ard was maprotiline. Plasma samples were extracted with n-hexane and isopropyl alcohol with fluorimetric detection （ λex 276 nm, λem 596 nm）. Results The linear range of venlafaxine in human plasma was 10 - 800ng.ml^-1 （ r = 0. 999 9 ）. The lowest detectable plasma concentration was 16.99ng.ml^-1 （ S/N 〉 3 ）. The extraction and relative recoveries of venlafaxine over plasma concentration 30,150,600ng.ml^-1 were 81.51% - 91.08% and 98.7 % 112.6 % respectively. The RSD of within-day and between-day were less than 12% and 10% （ n = 5 ）, respectively. The parameters： t 1/2（6.57 ±2.81）h, T max（3. 11 ±0.93）h, Cmax（273.38±75.44） ng.ml^-1, AUC（0-t） （2 237.54 ±816.67）ng.h.ml^-1 ,AUC（0-∞） （2 456.13 ∞838.30） ng·h·ml^-1. Conclusion The method is proved to be convenient, specific, sensitive enough to be applied to pharmaeokinetie studies of venlafaxine in human plasma.