亮菌甲素及其前药大鼠血浆药动学参数的比较  

Comparison of pharmacokinetic parameters of armillarisin A and its prodrug in rat plasma

作　　者：林彦凝 雷硕 陈明明[2] 赵龙山[1] 陈晓辉[1] LIN Yanning;LEI Shuo;CHEN Mingming;ZHAO Longshan;CHEN Xiaohui(School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;Shenyang Military Institute for Drug and Instrument Control, Shenyang 110026, China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]沈阳军区药品仪器检验所,辽宁沈阳110026

出　　处：《沈阳药科大学学报》2018年第6期448-452,459,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立测定大鼠血浆中亮菌甲素质量浓度的方法,比较亮菌甲素与其结构改造后亮菌甲素L-缬氨酸单酯盐酸盐的药物动力学参数差异,为亮菌甲素的化学结构改造和前药设计提供依据。方法采用UPLC-MS/MS法。色谱柱为Acquity UPLC BEH C18(50 mm×2.1 mm I.D,1.7 m)柱;内标物为苄氟噻嗪;流动相为乙腈-5 mmol醋酸铵水溶液(体积比20∶80);柱温为35℃;流速为0.20 m L·min^(-1);检测质核比为m/z 232.98→m/z 132.8(亮甲菌素)和m/z 420.2→m/z 289.1(内标物质苄氟噻嗪)。结果分别给予两种药物后,大鼠血浆中亮菌甲素的药动学参数口服亮菌甲素后AUC0-∞为308.8μg·h·L^(-1),t_(1/2)为0.387 h;口服亮菌甲素L-缬氨酸单酯盐酸盐为AUC0-∞为445.6μg·h·L^(-1),t_(1/2)为0.392 h。结论本方法可用于亮菌甲素血药质量浓度测定及药物动力学研究。Objective To establish an UPLC-MS/MS method for detecting the concentration of armillarisin A in the plasma,and to investigatd the effects of oral administration of armillarisin A or prodrug on the pharmacokinetics of armiharisin A in rats. Methods The ltra-performance liquid chromatography-tandem mass spectrometry（ UPLC-MS/MS） was used to detect the concentration of armillarisin A in the plasma. A Waters ACQUITY UPLC BEH C18 column（ 50 mm × 2. 1 mm,1. 7 μm） was employed in the study.Bendroflumethiazide was used as the internal standard. The mobile phase was consisted of acetonitrile（ A）and 0. 05% ammonium acetate solution（ B）. The column temperature was maintained at 35 ℃. The current velocity of mobile phase is 0. 2 m L·min^（-1）. Quantification was performed using multiple reaction-monitoring（ MRM）,the MRMtransitions were m/z 233. 2 →m/z 132. 8 for armiharisin A,m/z 420. 2 →289. 1 for Bendroflumethiazide（ IS）. Results The pharmacokinetic parameters of armiharisin A was AUC0-∞：308. 8 μg·h·L^（-1）,t1/2： 0. 387 h for oral armiharisin A; The pharmacokinetic parameters of armiharisin A was AUC0-∞： 445. 6 μg·h·L^（-1）,t1/2： 0. 392 h for oral armillarisin a L-valine ester hydrochloride. Conclusion We develope a fast and sensitive UPLC-MS/MS method for the determination of armiharisin A concentrations in rat plasma. The method is successfully applied to compare the pharmacokinetic behaviours after oral administration of armiharisin A and prodrug in rat. The results indicate that armiharisin A is esterified by Lvaline,can significantly increased absorption effect and blood concentration of armiharisin A. The reform of armiharisin A can eliminate the shortcoming of armiharisin A in clinic.

关 键 词：亮菌甲素 UPLC-MS/MS 前药 药物动力学 

分 类 号：R917[医药卫生—药物分析学]