高效液相色谱法同时测定动物血浆中萘哌地尔及其主要代谢产物浓度

为研究大鼠口服萘哌地尔的药代动力学规律,建立了同时测定萘哌地尔及其去甲基代谢产物浓度的高效液相色谱法。以甲醇、乙腈以及0.02mol·L^-1磷酸二氢钾溶液为流动相,RP-C₁₈为固定相,普萘洛尔作内标,紫外定量波长240nm。此条件下内标物、去甲基物和原药的保留时间分别为6.2,7.6和10.3min;绝对回收率分别为97.4%,86.6%和86.1%。去甲基物和原药在10～800ng·ml^-1血浆浓度范围内线性关系良好,γ=0.9998,最低检测浓度分别为8ng·ml^-1和5ng·ml^-1;日内和日间的相对标准偏差(RSD)均分别小于6.3%和11.6%(n=5)。并用此法研究了大鼠单次口服萘哌地尔后两者的药时规律。

DETERMINATION OF NAFTOPIDIL AND ITS MAIN METABOLITE IN PLASMA BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

A method was developed for the determination of naftopidil (NAF) and its main metabolite desmethyl-naftopidil (DMN) in plasma by HPLC. A mixture of methanol, acetonitrile and 0.02 mol.L-1 K2HPO4 solution was used as mobile phase. Stationary phase was RP-C18. Propranolol was chosen as internal standard (IS), and the detector wavelength was 240 nm. Under these conditions, the retention times of IS, DMN and NAF were 6.2, 7.6 and 10.5 min respectively. Absolute recoveries from plasma were up to 93.4% (IS), 76.8% (DMN) and 80.2% (NAF). The assay was linear for DMN and NAF in the range of 10-800 ng.ml-1 plasma concentration, gamma = 0.9998. The lowest detection limits were 8 ng.ml-1 (DMN) and 5 ng.ml-1 (NAF), and the precisions within-day and day-to-day were no more than 6.3% for MDN and 11.6% for NAF. The drug concentration-time pattern of these two substances was also studied with this method. Result showed that naftopidil was quickly absorbed after p.o. and the concentration-time data were fitted to two compartment model, with half life (T1/2 beta) of 8.13 h.