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目的建立高效液相色谱(HPLC)法测定小鼠血清中痂囊腔菌素A的浓度,考察其在小鼠体内的药动学特征。方法 60只小鼠,雌雄各半,痂囊腔菌素A 30.0 mg灌胃后,于不同时间点分取血浆,采用HPLC分别测定血清样品中痂囊腔菌素A浓度,用DAS 3.0.8软件计算药动学参数。结果痂囊腔菌素A在10.0~800.0μg.L-1内线性关系良好(r=0.999 6),日内和日间RSD<7.0%,提取回收率为89.2%~92.4%,方法回收率为100.1%~100.6%。痂囊腔菌素A在小鼠体内的主要药动学参数:AUC0-t为(16 697.8±873.0)μg.L.h-1,MRT0-t为(3.8±0.0)h,t■z为(3.6±0.0)h,tmax为(1.0±0.0)h,CLz/F为(1.8±0.0)L.h-1,ρmax为(5 889.3±135.9)μg.L-1。结论本法简便、灵敏、重现性好。痂囊腔菌素A在小鼠体内药动学过程符合二室模型。
OBJECTIVE To establish a HPLC method for the determination of cystatin A concentration in mouse serum and investigate its pharmacokinetic characteristics in mice. Methods Sixty mice, male and female, were randomly divided into three groups. The plasma concentrations of cystatin A (30.0 mg) after intragastric administration were measured at different time points. The concentrations of cystatin A in serum samples were determined by HPLC, Software calculates pharmacokinetic parameters. Results Cystatin A had a good linearity (r = 0.999 6) within the range of 10.0-800.0 μg.L-1 with an RSD of less than 7.0% and an average recovery of 89.2% -92.4%. The recovery rate was 100.1% ~ 100.6%. The main pharmacokinetic parameters of cystatin A in mice were: AUC0-t (16 697.8 ± 873.0) μg.Lh-1, MRT0-t was 3.8 ± 0.0 h, tz was 3.6 ± 0.0) h, tmax was (1.0 ± 0.0) h, CLz / F was (1.8 ± 0.0) Lh-1 and ρmax was (5 889.3 ± 135.9) μg.L-1. Conclusion This method is simple, sensitive and reproducible. Cystatin A in mice follows the two-compartment model of pharmacokinetics.