HPLCMS法测定兔血浆与组织中丹参素异丙酯的含量.docVIP

HPLCMS法测定兔血浆和组织中丹参素异丙酯的含量 （作者:___________单位: ___________邮编: ___________） 作者：张群正，李仲瑾，王世祥，南叶飞，于洁，郑晓晖 【摘要】 　　目的 建立兔血浆及组织中β(3,4二羟基苯基)α羟基丙酸异丙酯(丹参素异丙酯)的高效液相色谱电喷雾离子阱质谱(LCESIMSn)测定新方法。方法 采取液液萃取法处理血浆及组织样品，以4羟基苯甲酸甲酯为内标，LCESIMSn多级反应模式测定血浆及组织中丹参素异丙酯的含量。结果 丹参素异丙酯在血浆、心、肝、脾、肺、肾和脑中的检出限分别为：0.54、1.08、1.20、1.62、2.15、1.12、1.36ng/mL，线性范围分别为：0.20～400、0.10～200、0.01～100、0.02～400、0.20～800、0.01～100和0.05～100μg/mL，日内、日间精密度的相对标准偏差均小于10%，方法平均回收率在89.5%～107.4%范围内。结论 该分析方法灵敏度高、专属性好，为丹参素异丙酯的非临床和临床药代动力学研究提供一种方法学参考。 【关键词】 丹参素异丙酯；HPLCMS；药代动力学 　　ABSTRACT: Objective To establish a new method for the determination of isopropyl 3(3,4dihydroxyphenyl)2hydroxypropanoate (IDHP) in plasma and tissue in rabbits by high performance liquid chromatographyelectrospray iontrap mass (HPLCESIMSn). Methods Plasma and tissue samples were pretreated by liquidliquid method, methyl 4hydroxybenzoate was used as the internal standard, and the multireaction mode was applied to determine the concentration of IDHP in plasma and tissue samples. Results The detecting limits of IDHP in plasma, heart, liver, spleen, lung, kidney and brain were 0.54, 1.08, 1.20, 1.62, 2.15, 1.12 and 1.36ng/mL, respectively; the linear ranges were 0.20-400.0, 0.10-200.0, 0.01-100.0, 0.02-400.0, 0.20-800.0, 0.01-100.0 and 0.05-100.0μg/mL, respectively. The relative deviations for inter and intraday precision were all less than 10%; the average recoveries of the proposed method were within the range of 89.5% to 107.4%. Conclusion The proposed method has the merits of being sensitive and specific, and can be applied in investigating preclinical and clinical pharmacokinetics of IDHP. 　　KEY WORDS: isopropyl 3(3,4dihydroxyphenyl)2 hydroxypropanoate; HPLCMS; pharmacokinetics 　　β(3,4二羟基苯基)α羟基丙酸异丙酯(丹参素异丙酯，图1)是含服复方丹参滴丸后丹参在体内的活性代谢产物之一[12]。丹参素异丙酯具有良好扩张血管、改善脑供血、降低脑梗死面积和减轻水肿等作用，可作为一类新药候选药物进行研究开发[34]。本文旨在建立一种灵敏、快速的含量测定方法，测定丹参素异丙酯的血药浓度及组织分布，为后期非临床及临床药代动力学研究提供方法学参考。 　　1 材料与方法 　　1.1 实验动物 　　新西兰大白兔12只，体重2.0～2.2kg，雌雄各半，由西安交