人血浆中盐酸伊托必利含量测定及药物动力学研究

Determination of Itopride Hydrochloride in Human Plasma and Its Pharmacokinetics Parameters by HPLC

目的:建立一种测定人血浆中盐酸伊托必利血药浓度的反相高效液相色谱法,并用该法研究盐酸伊托必利颗粒的人体药物动力学。方法:采用外标法,血样经乙醚氢氧化钠混合溶剂提取后,以nucleosilC18250mm×4.6mm,5μm色谱柱为固定相,乙腈磷酸二氢钾为流动相,在257nm波长处定量检测。结果:血药浓度在10.0～1600.0ng·ml-1范围内线性关系良好,最低检测浓度为10.0ng·ml-1。日内、日间精密度RSD(%)均小于7%,低、中、高浓度(20,100,800ng·ml-1)的相对回收率分别为106.3%,104.6%,102.8%。用该法检测了20名健康受试者服用盐酸伊托必利颗粒后不同时间的血药浓度变化,并计算了有关药物动力学参数。结论:此方法简便、快速、精确,适用于伊托必利的血药浓度检测和药物动力学研究。

Objective: To establish a sensitive and simple reversed-phase high performance liquid chromatography method (RP-HPLC) to determine the concentration of itopride hydrochloride in human plasma and study the pharmacokinetics of its granules in human body. Method: Itopride hydrochloride in plasma was extracted with the mixed solvent of ether and sodium hydroxide, and then measured by RP-HPLC using a nucleosil C_(18) reverse phase column as stationary phase and acetonitrile-phosphate buffer as mobile phase. Itopride hydrochloride was quantified, the wavelength was at 257 nm. Result: The calibration curve was linear in the range from 10 ng·ml^(-1) to 1600 ng·ml^(-1)with a regression coefficient of (0.9995) and the lower limit of detection of itopride hydrochloride in plasma was 10 ng·ml^(-1). The both RSDs of intra-day and inter-day of were less than 7%, and the recoveries of itopride hydrochloride at the concentrations being 20,100 and 800 ng·ml^(-1) were (106.3%),(104.6% ),(102.8%), respectively. The method has been used to determine itopride hydrochloride in the plasma of twenty volunteers and the parameters of pharmacokinetics were calculated. Conclusion: The results demonstrated that this method was rapid and accurate, and can be applied to determine the plasma concentration of itopride and study its pharmacokinetics.