岩舒注射液4种生物碱类成分Beagel犬 体内药动学研究

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。

Pharmacokinetic of four alkaloids of Yanshu injection in Beagel dogs

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-H₂O 90:10 as the mobile phase. The plasma concentration of four kinds of alkaloids were calculated in dog plasma by detection of healthy dogs given Yanshu injection fluid after in twelve hours of plasma samples, All data of concentration-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 more than 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 alkaloids in rats meet the two-compartment open pharmacokinetic model, C_max and the concentration of the original liquid in the proportion of the basic line,the AUC _0-∞ of matrine and oxymatrine, sophocarpine and oxysophocarpine compared to the original both in the proportion of liquid increases, the MRT_0-∞ and t_1/2z of matrine and sophocarpine were less than oxymatrine and oxysophocarpine; four kinds of alkaloids apparent volume of distribution matrine> oxymatrine, sophocarpine> oxysophocarpine. Conclusion: A method with high recovery rate and good stabilitywas established to determine the blood concentration of MT, OMT, SP, OSP in Yanshu injection and applied in its pharmacokinetics successfully.