丹参和三七多种有效成分在大鼠体内的药物动力学研究

Pharmacokinetic Analysis of Multiple Active Components from Radix Salviae Miltiorrhizae and Radix Notoginseng in Rats Plasma

目的建立大鼠体内丹参素、丹酚酸B、隐丹参酮、丹参酮ⅡA及三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1的HPLC-ESI-MS分析方法,并用于复方丹参方的药物动力学研究。方法应用高效液相色谱三重四级杆质谱联用法测定丹参和三七多种有效成分血药浓度,以乙腈-0.1%甲酸溶液为流动相,色谱柱:Agilent C18(5μm,150 mm×4.6 mm),柱温:30℃,流速为0.5 mL.min-1。结果以电喷雾(ESI)正、负离子两种模式能有效实现丹参和三七中有效成分的分离。7种成分的峰面积与其在血样中的浓度线性关系良好(r>0.9684);平均回收率为70.09%～114.17%。7种成分均符合二室模型。结论该方法可用于复方丹参方的药物动力学研究。

Objective To develop sensitive and specific HPLC-ESI-MS methods for measurement of plasma tanshinol（TSN）,salvianolic acid B（SAB）,cryptotanshinone（CTS）,tanshinone IIA（TSⅡA）,notoginsenoside（R1）,ginsenoside（Rg1）,ginsenoside（Rb1） in supporting the pharmacokinetic evaluation of the compound Salvia recipes.Methods HPLC triple quadrupole mass spectrometric method was applied to determine the plasma concentration of the active Components in Radix Salviae Miltiorrhizae and Radix Notoginseng in rats plasma.Assay was performed on a reversed-phase Agilent C18（5 μm,150 mm ×4.6 mm）column with acetonitrile and 0.1 % formic acid solution as mobile phase,flow rate being 0.5 mL·min-1,and with column temperature at 30 ℃.Results The negative and positive ion ESI gave high ionization efficiency for the analytes.Provided good reproducibility for the quantification of seven components,all the compounds showed good linearity（r 〉0.9684） in the range of the test concentration,and the average recoveries of the method were between 70.09 %～121.22 %,respectively.The results indicated that seven major active components in rats could be described by a two-compartment model.Conclusion Sensitive and specific HPLC-MS methods are developed and validated,which are applicable to pharmacokinetic evaluation of compound Salvia recipes.