绒盖牛肝菌酸HPLC检测方法的建立及在大鼠体内的药代动力学

HPLC Method Developed to Determine the Pharmacokinetics of Xerocomic Acid in Rats

为建立绒盖牛肝菌酸血药浓度和各主要组织的HPLC检测方法,考察绒盖牛肝菌酸在大鼠体内的药代动力学和组织分布特点。采用Agilent ZORBAX Eclipse XDB-C18 column色谱柱(4.6 mm×250 mm,0.5μm)分离,以V(甲醇)∶V(水)=75∶25为流动相,流速1.0 m L/min,柱温25℃,检测波长243 nm。研究结果表明大鼠血浆及肝组织中的内源性物质均不干扰样品的测定,线性关系良好,大鼠灌胃绒盖牛肝菌酸符合一室模型,主要药代动力学参数Tmax为(0.76±0.21)h,Cmax为(8.76±0.81)μg/m L,t1/2为(0.18±0.28)h,AUC0-inf为(102.95±0.78)μg/(m L·h),大鼠尾静脉注射绒盖牛肝菌酸符合二室模型,主要药代动力学参数t1/2为(0.33±0.71)h,AUC_(0-inf)为(34.14±2.38)μg/(m L·h)。该方法简单快速,准确可靠,符合生物样品的测定要求,并明确了绒盖牛肝菌酸在大鼠体内的药代动力学和组织分布特征。

The goal of this study was to establish a method for determining xerocomic acid in plasma and tissues of rats, and to study its pharmacokinetic characteristics and tissue distribution characteristics after＇ intragastric administration and intravenous injection. The concentration of xerocomic acid in plasma and tissues of rats were analyzed by HPLC with Agilent ZORBAX Eclipse XDB- C18 column （4.6 min×250 ram, 0.5 μm） with the mobile phase of methanol-water （75 ： 25）, the temperature of column was 25℃, the flow rate was set at 1.0 mL/min, and the UV detector was set at243 nm. The endogenous ingredients in plasma and liver tissue showed no interference to the determination. The curves of average concentration-time for determining xerocomic acid after intragastric administration was fit to one compartment model. The primary pharmacokinetic pharameters were： Tmax（0.76±0.21 ） h, Cinax （ 8.76±0.81 ） μg/mL, tl/2（ 0.18±0.28 ） h, AUC0-inf（ 102.95± 0.78） μg/（mL-h）. The curves of average concentration-time for determining xerocomic acid after intravenous injection was fit to two compartment model. The primary pharmacokinetic pharameters were ： t1/2（0.33±0.71） h, AUC0-in（34.14±2.38） μg/（ mL· h）. The HPLC method was proved to meet the requirements of biological sample analyses owing to its rapid, sensitive and accurate. In addition, it was the first time to study the pharmacoineic characters and tissue distribution of xerocomic acid in rats, providing the basis for future drug discovery and study on pharmacological effects and mechanism of action （MOA） of xerocomic acid.