复方苦参注射液4种生物碱大鼠体内药动学研究  

Study on the pharmacokinetics of 4 alkaloids of Compound Matrine Injections in rats

作　　者：刘继平[1,2] 薛梅[3] 黄鑫[3] 江振洲[3,4] 张陆勇[3,5] 马世平[1] 

机构地区：[1]中国药科大学中药药理教研室,南京210009 [2]陕西中医学院药理教研室,咸阳712046 [3]中国药科大学江苏省新药筛选中心,南京210009 [4]药物质量与安全预警教育部重点实验室中国药科大学,南京210009 [5]中国药科大学江苏省药效研究与评价服务中心,南京210009

出　　处：《西北药学杂志》2012年第1期57-60,共4页Northwest Pharmaceutical Journal

基　　金：十一五"重大新药创制"科技重大专项(编号:2008ZX09202-009);陕西省教育厅自然科学专项(编号:2010JK498)

摘　　要：目的建立LC-MS法测定大鼠血浆中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱的质量浓度,研究复方苦参注射液在大鼠体内药动学过程及其参数。方法在血浆样品中加入内标,采用氯仿提取处理,以甲醇-0.2mL.L-1甲酸水溶液-10mmol.L-1NH4Ac水溶液(85∶7.5∶7.5)为流动相;VP-ODS柱分离,检测健康大鼠iv 2g.kg-1复方苦参注射液后12h内血浆样品中4种生物碱的质量浓度,用DAS 2.0药动学程序处理4种生物碱的血药浓度-时间数据。结果静注复方苦参注射液后,4种生物碱在大鼠体内的药代动力学符合二室开放模型,Cmax与原药液中质量浓度比例基本相符,苦参碱和氧化苦参碱AUC(0-∞)较为相近;苦参碱和槐果碱K12分别约为K21的2倍多,氧化槐果碱为3倍多,氧化苦参碱二者基本相近;表观分布容积顺序为槐果碱>氧化槐果碱>苦参碱>氧化苦参碱;氧化苦参碱t1/2β最短;苦参碱和槐果碱MRT(0-∞)较大,氧化苦参碱最小。结论氧化苦参碱部分代谢为苦参碱而增加了后者的血药浓度;氧化苦参碱主要分布在血液,消除最快,而其他3种生物碱会分布到组织;苦参碱、槐果碱和氧化槐果碱从中央室转运到周边室较为迅速,而氧化苦参碱转运速度相等。Objective To study the pharmacokinetics of Compound Matrine Injections in rats.Methods A sensitive and reproducible LC-MS method for quantitative determination of matrine,oxymatrine,sophocarpine and oxysophocarpine in rat's plasma was developed and validated using monocrotaline as an internal standard after iv of Compound Matrine Injections.The separation of plasma samples was performed on a VP-ODS column by isocratic elution with methanol-10 mmol·L-1 ammonium acetate-0.2 mL·L-1 formic acid-water(85∶7.5∶7.5) as the mobile phase.The plasma concentration of four kinds of alkaloids was calculated in rat plasma by detection of healthy rats given Compound Matrine Injections in twelve hours.All data of concentration-time of four kinds of alkaloids were treated with pharmacokinetics program DAS 2.0.Results Iv 2 g·kg-1 Compound Matrine Injections,four kinds of alkaloids in rats met the two-compartments open pharmacokinetic model;Cmax and the concentration of the original liquid in the proportion of the basic line,matrine and oxymatrine AUC(0-∞) were similar to that of injection;K12 of matrine and sophocarpine were approximately 2 folds more than K21 while oxysophocarpine was 3 folds,and oxymatrine was similar;apparent volume of distribution was sophocarpine> oxysophocarpine> matrine> oxymatrine;t1/2β of oxymatrine was minimum;MRT(0-∞) of matrine and sophocarpine was greater than that of oxymatrine.Conclusion Oxidative metabolism of matrine increased the blood concentration of oxymatrine;oxymatrine was mainly in the blood,while the other three kinds of alkaloids were distributed to the organs;and oxysophocarpine transfered from central compartment to peripheral compartment more quickly than matrine and sophocarpin did.

关 键 词：复方苦参注射液 液相色谱/质谱联用 药动学 

分 类 号：R285.5[医药卫生—中药学]