中国中药杂志

2009, v.34(10) 1276-1280

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LC-MS-MS测定黄连解毒汤中3种生物碱在大鼠血清的含量及其药代动力学研究
Pharmacokinetics of three alkaloids in Huanglianjiedu dcoction in rat serum by LC-MS-MS

吴晓霞;彭娟;范斌;于友华;
WU Xiaoxia,PENG Juan,FAN Bin,YU Youhua (Experimental Research Centre,China Academy of Chinese Medical Sciences,Beijing 100700,China)

摘要(Abstract):

目的:建立灵敏、特异、准确、可靠的药根碱、巴马汀、小檗碱在大鼠血清中液质联用(LC-MS-MS)分析方法,用于黄连解毒汤中3种生物碱在正常大鼠体内药代动力学研究。方法:优化药根碱、巴马汀、小檗碱及内标延胡索乙素质谱检测条件,确定相关条件并开展方法学考察。正常大鼠灌胃给予黄连解毒汤,经时取血,样品经处理后将该方法用于3种成分的测定。DAS药代动力学软件拟合房室模型,计算药动参数。结果:在ESI(+)离子化条件下采用MRM工作模式,用m/z338~322,351.9~308,336~319.8来分别检测药根碱、巴马汀、小檗碱,同时以m/z356.1~192.1来检测内标延胡索乙素。药根碱在0.2~25μg.L-1、巴马汀、小檗碱在0.4~50μg.L-1呈良好线性关系。3种生物碱在高、中、低3个浓度的准确度、精密度、稳定性等均符合要求。药根碱、巴马汀、小檗碱在正常大鼠体内药动学过程符合一室开放模型。结论:应用LC-MS-S技术建立了测定药根碱、巴马汀、小檗碱血药浓度的方法,并成功应用于黄连解毒汤正常大鼠体内这3个成分的药动学研究,为中药复方药动学研究提供了可以借鉴的分析方法。
Objective:To develop a sensitive and reliable high-performance liquid chromatography-tandem mass sepctrometry(LC-MS-MS) method for simultaneous determination of jatrorrhizine,palmatine and berberine in rat serum,and study the pharmacokinetics of the three alkaloids in rat serum after an intragastrical(ig) administration of Huanglianjiedu decoction to rat.Method: The optimal ionization and fragmentation conditions,as well as HPLC ones,to detect jatrorrhozine,palmatine and berberine were developed and validated.After the Huanglianjiedu decoction were administered to rats through ig route,LC-MS-MS method has been applied to the pharmacokinetic study of the three alkaloids in rat serum.DAS procedure was used to process concentration-time data.Result: The detection was performed by MRM mode via electrospray ionization(ESI) source operating in the positive ionization mode.The precursor-to-product ion transitions were at m/z 338-322 for jatrorrhozine,m/z 351.9-308 for palmatine,m/z 336-319.8 for berberine and m/z 356.1-192.1 for tetrahydropalmatine(IS) respectively.The method was linear over the concentration range of 0.2-25 μg·L-1 for jatrorrhozine,0.4-50 μg·L-1 for palmatine and berberine.The method was validated according to the requirements.The pharmacokinetic process of the three alkaloids after oral administration of Huanglianjiedu decoction was fitted to be a one-compartment model.Conclusion: The fully validated LC-MS-MS method has been successfully applied to the pharmacokinetic study of the three alkaloids in rat serum after oral administration of Huanglianjiedu decoction.

关键词(KeyWords): 黄连解毒汤;药根碱;巴马汀;小檗碱;液质联用;药代动力学
Huanglianjiedu decoction;jatrorrhizine;palmatine;berberine;LC-MS-MS;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(30873358)

作者(Author): 吴晓霞;彭娟;范斌;于友华;
WU Xiaoxia,PENG Juan,FAN Bin,YU Youhua (Experimental Research Centre,China Academy of Chinese Medical Sciences,Beijing 100700,China)

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