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

LIU Jiping1,2,XUE Mei3,HUANG Xin3,JIANG Zhenzhou3,4,ZHANG Luyong3,5,MA Shiping1(1.Department of Pharmacology of Chinese Materia Medica,China Pharmaceutical University,Nanjing 210009,China;2.Department of Pharmacology,Shaanxi University of Chinese Medicine,Xianyang 712046,China;3.Jiangsu Center for Drug Screening,China Pharmaceutical University,Nanjing 210009,China;4.Key Laboratory of Drug Quality Control and Pharmacovigilance Ministry of Education,China Pharmaceutical University,Nanjing 210009,China;5.Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing 210009,China)  
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.
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