内皮素受体拮抗剂CPU-0213 血药浓度的HPLC 测定法和药动学研究

目的: 建立内皮素受体拮抗剂CPU-0213 在小鼠和大鼠血清中的检测方法, 测定单次静脉注射(iv) CPU-0213 80 mg·kg^-1后在小鼠和大鼠体内的药代动力学。方法: 用HPLC 测定小鼠和大鼠血清中的药物浓度, 3P97 程序拟合药动学参数。结果: CPU-0213 在0.4～200 μg·L^-1的范围内呈良好的线性关系(r=0.9998), 最低检测浓度为35 μg·L^-1。日内差小于2.7 %, 日间差小于6.3 %, 方法回收率大于95.9 %。CPU-0213 在小鼠和大鼠体内的药-时数据均符合二室模型, 消除半衰期分别为83.0±1.8 min 和96.6±11.5 min 。结论: 该方法灵敏、简单, 专属性强, 重现性好。单次iv CPU-021380 mg·kg^-1后, 在小鼠和大鼠体内的药代动力学未见种属差异性。

Pharmacokinetics of CPU-0213 in mice and rats after intravenous injection

AIM: To establish a method in determination of CPU-0213 in serum of mice and rats and to investigate the pharmacokinetics parameters after a single injection at the dose of 80 mg·kg^-1.METHODS: The concentration of CPU-0213 in serum was assayed by HPLC and the pharmacokinetics parameters were calculated by the program of 3P97.RESULTS: The linearity of CPU-0213 ranged from 0.4 to 200 mg·L^-1(r=0.9998) and the limit of quantity was 35 μg·L^-1.The RSD of intra-day was less than 2.7 %and that of inter-day was less than 6.3 %.The recovery was more than 95.9 %.The disposition was conformed to a two-compartment model. The T_1/2β of CPU-0213 in mice and rats were 83.0±1.8 and 96.6±11.5 min, respectively.CONCLUSION: The study provides a simple, stable and special method for determining of concentrations of CPU-0213 in serum of mice and rats.After intravenously injection of CPU-0213 at a single dose, there is no significantly difference in the pharmacokinetics patterns of CPU-0213 in mice and rats.