厚朴中苯乙醇苷类化合物厚朴苷A的大鼠体内药动学研究

目的:建立血浆样品中厚朴苷A的测定方法,研究厚朴苷A在大鼠体内的药动学特征。方法:大鼠经口服和尾静脉注射给药,以黄芩苷为内标,采用高效液相色谱法测定不同时间点大鼠血浆中的厚朴苷A浓度。使用岛津LC-20A高效液相色谱仪,色谱柱为Agilent Zobax SB-C18(250 mm×20 mm,5μm),甲醇/水溶液梯度洗脱(0~15 min,甲醇15%~85%),流速为1 mL·min~(-1)。采用DAS 2.0软件对所得的需要浓度进行拟合,计算相应的药动学参数。结果:大鼠经口服给药200 mg·kg~(-1)、尾静脉注射给药5 mg·kg~(-1),目标物质量浓度在0.3~100μg·mL~(-1),内线性关系良好(r=0.999 6),标准曲线定量下限为0.3μg·mL~(-1);批内精密度RSD7.1%,批间精密度RSD12.4%;准确度RE3.3%~5.9%;回收率83.5%~99.0%。大鼠经口服给药的药动学参数AUC(0-t)为(15.6±7.4)mg·h/L,CL为(14.5±6.1)L·h/kg,Vd为(13.5±2.8)L/kg,t1/2为(1.16±0.8)h。大鼠尾静脉注射给药的药动学参数AUC(0-t)为(17.8±9.9)mg·h/L,CL为(0.34±0.14)L·h/kg,Vd为(0.08±0.04)L/kg,t1/2为(0.15±0.03)h。结论:该实验建立了一种简便、准确、快速地测定厚朴苷A浓度的方法,首次报道了厚朴苷A在大鼠体内的药物代谢动力学特征。

Pharmacokinetics Study on Magnoloside A in Bark of Official Magnolia of Phenylethanoid Glycosidesin in Rats

Objective:To establish a method for the determination of Magnoloside A in plasma samples and to study the pharmacokinetic characteristics of Magnoloside A in rats.Methods:Rats by oral administration and intravenous injection with Magnoloside A as the internal standard used the high performance liquid chromatography to detect the concentrations of Magnoloside A in rat plasma at different time.Shimadzu LC-20A high performance liquid chromatograph was applied with a Agilent Zobax SB-C18column(250 mm×20 mm,5μm)by a gradient elution using(A)methanol-(B)water as the mobile phase 0 min(15%A)→15 min(85%A)and the flow rate was 1 mL·min~(-1).DAS 2.0 Software was applied to fit the blood concentration and calculate the corresponding pharmacokinetic parameters.Results:The rats were given at the concentrations of 200 mg·kg~(-1) and 5 mg·kg~(-1) by oral administration and intravenous injection respectively.The target blood quality concentrations showed good liner relations within the range of 0.3~100μg·mL-1(r=0.999 6),the lower limit of standard curve was 0.3μg·mL~(-1).RSD of with-run and between-run precisions was less than 7.1%and 12.4%.Accuracy RE ranged between 3.3%and 5.9%.The recovery rates ranged between 83.5%and 99.0%.Regarding the pharmacokinetic parameters of oral administration:(15.6±7.4)mg·h/L of AUC(0-t),(14.5±6.1)L·h/kg of CL,(13.5±2.8)L/kg of Vd,(1.16±0.8)h of t1/2.The parameters of intravenous injection:(17.8±9.9)mg·h/L of AUC(0-t),(0.34±0.14)L·h/kg of CL,(0.08±0.04)L/kg of Vd,(0.15±0.03)h of t1/2.Conclusion:We established a simple,rapid and accurate method to detect the blood concent rations of Magnoloside A and published the pharmacokinetics of Magnoloside A in rats for the first time.