盐酸二氧丙嗪血药浓度的测定及其在健康志愿者体内的药动学

Determination of dioxopromethazine hydrochloride in human plasma and its phar-macokinetics in Chinese healthy volunteers

目的检测人血浆中盐酸二氧丙嗪的浓度,并研究在健康志愿者中口服单剂量9 mg后的药动学特征。方法血浆样品经液-液萃取法提取处理,用高效液相色谱荧光检测法建立血浆中盐酸二氧丙嗪浓度的分析方法。结果盐酸二氧丙嗪在为0．5～75．0μg·L-1时线性关系良好(r=0．999 9),其血浆中的提取回收率>80％。日内、日间RSD分别<5％和<7％。盐酸二氧丙嗪浓度的血药浓度-时间曲线符合二室模型,主要药动学参数为:tmax为(2．17±1．70)h;ρmax为(31．07±5．83)μg·L-1;t1/2为(12．97±5．52)h。结论本方法灵敏度高,选择性好和重视性佳,可准确测定人血浆中盐酸二氧丙嗪的浓度。

AIM To determine the concentration of dioxopromethazine hydrochloride in human plasma and investigate its pharmacokinetics in healthy volunteers following oral administration of a single dose of 9 mg. METHODS Plasma samples were processed by liquid-liquid extraction and the plasma concentrations of dioxopromethazine hydrochloride were assayed by HPLC with fluorescence detection （HPLC-FLD）. RESULTS Assay linearity was obtained in the range of （0.5- 75.0）μg·L^-1（ r = 0.999 9）. The recovery of dioxopromethazine hydrochloride from human plasma was more than 80 %. The intra-day and inter-day relative standard deviations （RSDs） were less than 5% and less than 7%, respectively. The concentration-time curve was fitted to a two-compartment model. Its main pharmacokinetic parameters were as follows： tmax Was（2.17 ± 1.70 ） h; ρmax was （31.07 ±5.83 ） μg·L^-1 ; t1/2 was （ 12.97 ±5.52） h. CONCLUSION The method developed in this study is of high sensitivity, good selectivity and reproducibility for accurate determination of the plasma concentration of dioxopromethazine hydrochloride in human.