中国中药杂志

2008, (22) 2683-2687

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复方丹参制剂不同配伍对丹酚酸B在大鼠血浆中药代动力学参数的影响
Effect of different combinations of compound Danshen preparation on pharmacokinetic parameters of salvianolic acid B in rat plasma

林力;刘建勋;张颖;林成仁;李利群;
LIN Li,LIU Jian-xun,ZHANG Ying,LIN Cheng-ren,LI Li-qun(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

摘要(Abstract):

目的:建立检测大鼠血浆中丹酚酸B分析方法,并探讨复方丹参制剂不同配伍给药后对丹酚酸B的影响。方法:分别采用复方丹参制剂(双参通冠方)不同配伍方式灌胃给药,溶剂沉淀法提取含药血浆中的酚酸类成分,采用LC-MS-MS方法测定血药浓度,DAS软件对结果进行统计分析。结果:色谱采用Agilent SB-C18反相柱,流动相乙腈-甲醇-0.1%甲酸梯度洗脱,质谱采用MRM方式进行检测,丹酚酸B的线性范围为0.5~1000μg.L-1,R2=0.999,最低检测限为0.5μg.L-1,提取回收率为30.88%~38.18%,方法的精密度、准确度和稳定性均符合要求。结论:本方法操作简单、专属性强、灵敏度高、准确性好。药代动力学研究发现与单一丹参组分给药相比,配伍应用均可使丹酚酸B的AUC降低,表观分布容积和清除率增加。
Objective: A sensitive liquid chromatography-mass spectrometric(LC-MS) method for the quantification of salvianolic acid B in rat plasma was developed and validated.The effect of different combination on the salvianolic acid B were studied to investigate SSTG' pharmacokinetics mechanism.Method: Different combination methods were used for oral administration.The compounds were extracted by solvent in rat plasma and determined using LC-MS-MS method.The results were analysis by DAS software.Result: Chromatographic separation was achieved on a reversed-phase SB-C18 column with the mobile phase of acetonitrile-methanol-formic acid(0.1%) and step gradient elution resulted.The analytes were detected by using an electrospray negative ionization mass spectrometry in the MRM mode.The method showed excellent linearity over the concentration range 0.5-1 000 μg·L-1(R2=0.999).The low limit of quantification was 0.5 μg·L-1.The extract recoveries of analytes were from 30.88% to 38.18%.The precisions,the accuracy and the stability all meet the requirements for all analytes.The HPLC-MS-MS technique provided an excellent method for the quantification of SAB in rat plasma.Conclusion: The method is simple,sensitive and rapid.The plasma concentration of Rg1 and Re were too low to determine.Ginseng & Yanhusuo and Ginseng & Danshen combination can decrease the AUC value and increase the Vd and CL.

关键词(KeyWords): 丹酚酸B;药代动力学;液质联用;配伍
salvianoalic acid B;pharmacokinetics;LC-MS-MS;combination

Abstract:

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基金项目(Foundation): 国家科技支撑计划项目(2006BA108B04-08);; 国家中医药管理局课题(06-07ZP49);; 北京市优秀人才项目(20061D1600100402)

作者(Author): 林力;刘建勋;张颖;林成仁;李利群;
LIN Li,LIU Jian-xun,ZHANG Ying,LIN Cheng-ren,LI Li-qun(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

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