论文部分内容阅读
目的建立测定大鼠血浆中野黄芩素及其代谢产物葡萄糖醛酸结合物浓度的UPLC-MS/MS法,并讨论两者在大鼠体内的药代动力学过程。方法色谱采用Waters BEH C18色谱柱,流动相为0.1%甲酸乙腈-0.1%甲酸水溶液,梯度洗脱,质谱采用多反应监测(MRM)进行正离子检测野黄芩素。大鼠静脉给予野黄芩素,测定给药后不同时间的野黄芩素的血药浓度;采用酶解方式间接测定野黄芩素葡萄糖醛酸结合物的血药浓度,以DAS 2.0软件获得药动学参数。结果野黄芩素在0.116~28.2 mg·L-1呈良好线性相关,提取回收率为80.5%~90.0%,精密度、准确度、稳定性良好。药代动力学研究结果表明静脉给予野黄芩素后其原型及其葡萄糖醛酸结合物药代动力学过程均符合二室模型。结论本研究所建立的方法具有灵敏度高,重现性好,操作简便等特点,可用于同时测定野黄芩素及其葡萄糖醛酸结合物在体内的浓度,便于原型药物及其代谢物产物的药动学研究。
OBJECTIVE To establish a UPLC-MS / MS method for the determination of the concentration of baicalein and its metabolite glucuronide in rat plasma and to discuss its pharmacokinetics in rats. Methods Waters BEH C18 column was used. The mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The mobile phase was eluted with gradient elution. Mass spectrometry was used for the detection of baicalein by multiple reaction monitoring (MRM). The rats were given intravenous baicalein, and the plasma concentration of baicalein was determined at different times after administration. The plasma concentration of baicalein glucuronic acid conjugate was determined indirectly by enzymolysis method. The pharmacokinetics parameter. RESULTS: Baicalein was linearly correlated with 0.116-28.2 mg · L-1 and the recoveries were 80.5% -90.0%. The precision, accuracy and stability of baicalein were good. Pharmacokinetic study results showed that after intravenous administration of baicalein its prototype and its glucuronic acid conjugate pharmacokinetic process are in line with the two-compartment model. Conclusion The method established in this study has the characteristics of high sensitivity, good reproducibility and easy operation. It can be used to determine the concentration of baicalein and glucuronic acid conjugates in vivo simultaneously, which is convenient for the manufacture of drugs and their metabolites Kinematics research.