岩舒注射液4种生物碱类成分Beagel犬体内药动学研究  

Pharmacokinetic of four alkaloids of Yanshu injection in Beagel dogs

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

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

出　　处：《中国中药杂志》2012年第12期1845-1849,共5页China Journal of Chinese Materia Medica

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

摘　　要：目的:建立LC-MS法测定Beagel犬血浆中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱的浓度,研究岩舒注射液在Beagel犬体内药动学过程及其参数。方法:以野百合碱做内标,三氯甲烷提取,甲醇-10 mmol醋酸铵0.02%甲酸水溶液90∶10为流动相,CN柱分离,检测Beagel犬iv 1.2 g.kg-1岩舒注射液后12 h内血浆样品中4种生物碱的浓度,用DAS 2.0药动学程序处理血药浓度-时间数据,分析药动学参数。结果:苦参碱、氧化苦参碱、槐果碱、氧化槐果碱分别在0.01～16.0,0.02～60.0,0.01～4.0,0.02～16.0 mg.L-1具有良好的线性关系,平均回收率均大于90%,精密度试验RSD小于6.4%,稳定性试验RSD小于4.6%;静注岩舒注射液后,4种生物碱在Beagel犬体内的药代动力学符合二室开放模型,Cmax与原药液中浓度比例基本相符;苦参碱和氧化苦参碱、槐果碱和氧化槐果碱的AUC0-∞与原药液中的比例相比均有增大,苦参碱和槐果碱MRT0-∞和t1/2z分别小于氧化苦参碱和氧化槐果碱;4种生物碱表观分布容积苦参碱>氧化苦参碱,槐果碱>氧化槐果碱。结论:该方法用于岩舒注射液中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱血药浓度的测定准确、灵敏、稳定性好、回收率高,适合其药动学研究。Objective ： For studying the pharmacokinetic of Yanshu injections in Beagel dogs, a sensitive and reproducible LC- MS method for quantitative determination of matrine, oxymatrine, sophocarpine and oxysophocarpine in dog＇s plasma were developed and validated using monocrotaline as an internal standard after iv of Yanshu injections （ Sophorae Flavescentis Radix and Heterosmilacis Japonicae Rhizoma）. Method： The separation of plasma samples was performed on a CN column by isocratic elution with methanol-10 mmol ·L^-1 NH4Ac-0. 02% HCOOH-H20 90：10 as the mobile phase. The plasma concentration of four kinds of alkaloids were calcu- lated in dog plasma by detection of healthy dogs given Yanshu injection fluid after in twelve hours of plasma samples, All data of con- centration-time of four kinds of alkaloids were treated with pharmacokinetics program DAS 2.0. Result： MT, OMT, SP and OSP have a good linear relationship in 0.01-16. 0, 0. 02-60. 0, 0. 01-4. 0, 0. 02-16.0 mg·L^-1 , respectively. The average recoveries were morethan 90% and the RSD of precision and stability of the test were less than 6.4% iv 1.2 g·kg^-1 Yanshu injection, four kinds of alka- loids in rats meet the two-compartment open pharmacokinetic model, Cm,x and the concentration of the original liquid in the proportion of the basic line, the AUC0-∞ of matrine and oxymatrine, sophocarpine and oxysophocarpine compared to the original both in the propor- tion of liquid increases, the MRT0-∞ and t1/2x of matrine and sophocarpine were Xess than oxymatrine and oxysophocarpine ; four kinds of alkaloids apparent volume of distribution matrine 〉 oxymatriue, sophocarpine 〉 oxysophocarpine. Conclusion： A method with high re- covery rate and good stabilitywas established to determine the blood concentration of MT, OMT, SP, OSP in Yanshu injection and ap- plied in its pharmacokinetics successfully.

关 键 词：岩舒注射液 液相色谱/质谱联用 药动学 

分 类 号：R285.5[医药卫生—中药学]