复方苦参注射液大鼠胆汁、尿液排泄研究  

Studies on Bile and Urine Excretion of Compound Radix Sophorae Flavescentis Injection in Rats

作　　者：刘继平[1,2] 黄鑫[3] 薛梅[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,陕西咸阳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：《中药新药与临床药理》2011年第4期424-428,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：十一五重大新药创制科技重大专项(2008ZX09202-009);陕西省教育厅项目(2010JK498)

摘　　要：目的建立大鼠胆汁和尿液中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱含量的LC-MS测定方法,研究复方苦参注射液在大鼠胆汁和尿液的排泄情况。方法在胆汁和尿液样品中加入内标,采用氯仿提取处理,以甲醇∶10 mmol/L NH4Ac-0.02%HCOOH-水=90∶10(V∶V)为流动相;CN柱分离,检测健康大鼠给予复方苦参注射液后7个时间段的胆汁及5个时间段尿液样品中4种生物碱的浓度,计算胆汁和尿液累积排泄量和累积排泄率。结果大鼠20 h内胆汁中4种生物碱的排泄率曲线逐渐走平;在胆汁中氧化苦参碱和氧化槐果碱的浓度分别高于苦参碱和槐果碱。72 h内,尿液4种生物碱排泄曲线基本达到平台,尿液中氧化苦参碱和氧化槐果碱的浓度和排泄量分别显著高于苦参碱和槐果碱,排泄到第3天各主要成分浓度均低于检测限。结论复方苦参注射液中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱主要通过肾脏以尿排泄为主,一部分通过胆汁排泄,但推测可通过肝肠循环方式再次进入体循环以尿排泄,并可能存在其他代谢物。Objective For studying the excretion of Compound Radix Sophorae Flavescentis Injection in rats, a sensitive and reproducible liquid chromatography-mass spectrum （LC-MS） method tbr quantitative determination of matrine, oxymatrine, sophocarpine and oxysophocarpine in the bile and urine of rats were developed and validated by using monocrotaline as an internal standard. Methods The separation of bile and urine samples was performed on a CN column with methanol ： 10 mmot NH4Ac-0.02 % HCOOH-H20 = 90 ： 10 （V ： V） as the mobile phase. The accu- mulative excretion and accumulative excretion rate of four kinds of alkaloids were calculated in the bile and urine after detection of the bile samples during 7 time periods and after detection of the urine samples during 5 time periods in healthy rats given Radix Sophorae Flavescentis injection fluid. Results Within 20 hours, the excretion of four alkaloids gradually tended to became steady, and the concentrations of oxymatrine and oxysophocarpine were higher than those of matrine and sophocarpine in the bile. Within 72 hours, the curve of urine excretion of four alkaloids reached to a plateau, and the concentrations of oxymatrine and oxysophocarpine were significantly higher than those of matrine and sophocarpine in the urine. The concentrations of the main components were below to the detection limit concentration till the third day. Conclusion The excretion of matrine, oxymatrine, sophocarpine and oxysophocarpine in Compound Radix Sophorae Flavescentis Injection is mainly by the urine through kidney. The excretion of some of the alkaloids is through the bile, but finally the alkaloids are probably through enterohepatic circulation to go back to the systemic circulation and then excrete through the urine, which may be in some other metabolites.

关 键 词：复方苦参注射液 液相色谱-质谱联用 胆汁排泄 尿液排泄 肝肠循环 

分 类 号：R285.5[医药卫生—中药学]