家兔血浆中替拉扎明的HPLC测定及药动学研究

建立家兔血浆中替拉扎踢（Tirapazaming，TPZ）测定的高效液相色谱法（HPLC），并进行TPZ在家兔体内的药代动力学研究。血浆样品用甲醇沉淀蛋白后进样；流动相为甲醇-50mmol／L磷酸二氢钠溶液（10：90，磷酸调pH6．5），在266nm波长处检测，按外标法进行血药浓度计算。在此色谱条件下，TPZ峰形良好，血浆内源性成分对药物测定无干扰；检测限为0．5ng，在血药浓度0．150～59．98mg／L范围内，浓度与峰面积有良好的线性关系，r=0．9995；方法回收率〉95％（n=3），日内精密度和日间精密度的RSD〈6%（n=5）。TPZ在家兔体内的血药浓度-时间曲线符合二室模型。该法灵敏、简便、准确，适用于TPZ在家兔体内的药代动力学研究。

Study on HPLC Determination Method and Pharmacokinetics of Tirapazaming in Rabbits

We have developed an HPLC method for the determination of tirapazaming (3-Amino-1,2,4-Benzotriazine -1,4-dioxide, TPZ) in rabbits and have studied the related pharmacokinetics in rabbits. After protein was precipitated, TPZ in plasma was determinated on HPLC with UV detection at 266 nm, and the mobile phase consisted of methyl alcohol and phosphoric buffer (10: 90, adjusted to pH6.5 +/- 0.1 with NaOH). TPZ and endogenous substances could be separated. Its calibration curve was linear (r=0.9995) within the range of 0.150-59. 98 mg/L, the detection limits was 0.5 ng (S/N>3), the recovery was more than 95% (n=3), the intra-day and inter-day precision was less than 6.0% (n = 5). The concentration-time curve of TPZ in rabbit plasma could be fitted to two-compartment model. These data indicate the method is sensitive, simple and reliabe. It is suitable for the pharmacokinetic study of TPZ in rabbits.