白花前胡丁素在大鼠体内的药动学研究

Study on Pharmacokinetics of Praeruptorin D in Rats in vivo

目的：建立白花前胡丁素（PD）的血浆浓度测定方法,研究PD在大鼠体内的药动学特征。方法：采用高效液相色谱法。色谱柱为Odyssil C18,流动相为甲醇-水（75∶25,V/V）,流速为0.8 ml/min,检测波长为323 nm,柱温为25℃,进样量为20μl。24只雄性SD大鼠随机均分为PD高、低剂量（20、10 mg/kg）组。大鼠尾iv给药0.016 7、0.083 3、0.166 7、0.25、0.5、0.75、1、1.5、2、3、4 h后眼眶采血测定血药浓度,采用3p87软件计算药动学参数。结果：PD检测质量浓度线性范围为0.05~51.2μg/ml（r2=1.000）,精密度试验的RSD均小于7.85%,方法回收率为83.12%~86.63%,提取回收率为80.19%~84.21%,稳定性试验的RSD均小于15%。PD高、低剂量组t1/2α分别为（0.128 6±0.052 1）、（0.118 5±0.054 6）h,t1/2β分别为（2.64±0.874）、（2.41±0.823 1）h,cmax分别为（14.981 2±5.831）、（9.012 8±1.576）μg/ml,tmax分别为（0.109 1±0.058 5）、（0.108 2±0.069 1）h,AUC0-4 h分别为（20.79±9.981）、（18.14±9.856）μg·h/ml,CL分别为（1.335 7±1.146）、（1.521 5±1.268）L·kg/h。结论：该方法灵敏度高、专属性强、操作简便、准确可靠,可应用于PD在大鼠体内的药动学特征研究。PD在大鼠体内的消除过程属于一级消除,符合二室模型。

OBJECTIVE： To establish a method for determining the plasma concentration of praeruptorin D （PD） and investigate the pharmacokinetic characteristics of PD in rats in vivo. METHODS： HPLC was adopted. The column was Odyssil Ct8 with the mobile phase of methanol-water （75 ： 25, V/V）, at the flow rate of 0.8 ml/min, with the detection wavelength of 323 nm, column temperature of 25 ℃ and the volume of 20 μl. 24 male SD rats were randomly divided into PD high and low dose groups （20 and 10 mg/kg）. The plasma concentration was determined by orbital blood 0.016 7, 0.083 3, 0.166 7, 0.25, 0.5, 0.75, 1, 1.5, 2, 3 and 4 h after their tails were iv given the drug, and 3p87 software was employed to calculate pharmacokinetic parameters. RE- SULTS： In the determination of PD, the quality concentration linear range was 0.05-51.2 gg/ml （r^2= 1.000）, the RSD of precision test was less than 7.85%, the method recovery was 83.12%-86.63%, the extraction recovery was 80.19%-84.21% and RSD of stability tests was less than 15%. The t1/2α in PD high and low dose groups were respectively （0.128 6 ± 0.052 1） h and （0.118 5 ± 0.054 6） h, t1/2α were respectively （2.64 ± 0.874） h and （2.41 ± 0.823） h, Cmax were respectively （14.981 2 ± 5.831） μg/ml and （9.012 8 ± 1.576） μg/ml, tmax were respectively （0.109 1 ± 0.058 5） h and （0.108 2 ± 0.069 1） h, AUC0-4h were respectively （20.79 ± 9.981） μg·h/ml and （18.14 ± 9.856） μg·h/ml and CL were respectively （1.335 7 ± 1.146） L·kg/h and （1.521 5 ± 1.268） L·kg/h. CONCLU- SIONS： The method is highly sensitive, exclusive, simple, accurate and reliable, and can be applied to study on the pharmacokinetic characteristics of PD in rats in vivo. The elimination of PD in rats was first-order elimination and compatible with two-compartment model.