Pharmacokinetics and tissue distribution study of schisandrin B in rats by ultra-fast liquid chromatography with tandem mass spectrometry.
Pharmacokinetics and tissue distribution study of schisandrin B in rats by ultra-fast liquid chromatography with tandem mass spectrometry.
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DOI：
10.1016/j.jpba.2013.01.041
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发表时间：
2013-05
影响因子：
3.4
通讯作者：
Heyun Zhu;Xiu-rong Zhang;J. Guan;Baiji Cui;Longshan Zhao;Xu Zhao
中科院分区：
文献类型：
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作者：
Heyun Zhu;Xiu-rong Zhang;J. Guan;Baiji Cui;Longshan Zhao;Xu Zhao
建立了一种快速、灵敏、高通量的超快速液相色谱-串联质谱法（UFLC-MS/MS），用于测定大鼠血浆及心、肝、脾、肺、肾等组织中五味子甲素B的浓度。采用蛋白沉淀法制备生物样品，在shim-pack XR-ODS C18柱上进行分离（75 mm × 3.0 mm，2.2μm），移动的流动相为甲醇-0.1%甲酸水溶液（85：15,采用API 3200 QTRAP质谱仪，电喷雾离子源，多反应监测（MRM）模式，对五味子醇甲B和欧前胡素进行质谱检测，质谱裂解峰分别为m/z 401.2→300.2和271.2→203.1（内标，IS）。血浆和组织匀浆在1- 500 ng/mL范围内线性关系良好（r≥0.9927）。定量下限（LLOQ）为1 ng/mL。该方法已成功应用于五味子甲素B在大鼠体内的药代动力学和组织分布研究。口服给药后，药动学曲线呈双峰型，提示可能存在肝肠循环。组织分布以肝脏含量最高，其次是肾脏，说明五味子乙素B主要在肝脏蓄积，肾脏排泄可能是主要消除途径。
A rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC–MS/MS) method was established and validated for the determination of schisandrin B in rat plasma and various tissues (including heart, liver, spleen, lung, and kidney). The biological samples were prepared by protein precipitation, and the separation was achieved on a shim-pack XR-ODS C18column (75mm×3.0mm, 2.2μm) with a mobile phase consisting of methanol–0.1% formic acid water (85:15, v/v) at a flow rate of 0.4mL/min. The MS/MS detection was performed on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization (ESI) source using multiple reactions monitoring (MRM) mode by monitoring the fragmentation of m/z 401.2→300.2 for schisandrin B and m/z 271.2→203.1 for imperatorin (internal standard, IS). The calibration curve was linear in the range of 1–500ng/mL for plasma and tissue homogenates (r≥0.9927). The lower limit of quantification (LLOQ) was 1ng/mL. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of schisandrin B after oral administration to rats. The pharmacokinetic curve showed double peaks after oral administration, which demonstrated that a hepatoenteral circulation may exist. Tissue distribution showed the highest level was observed in liver, then in kidney, which indicated schisandrin B was mainly accumulated in liver and renal excretion might be a main elimination route.