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大鼠血浆中姜黄素的高效液相色谱分析:应用于姜黄素聚合物胶束制剂的药代动力学研究

High-performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin.

作者信息

Ma Zengshuan, Shayeganpour Anooshirvan, Brocks Dion R, Lavasanifar Afsaneh, Samuel John

机构信息

University of Alberta, Edmonton, Alberta, Canada T6G 2N8.

出版信息

Biomed Chromatogr. 2007 May;21(5):546-52. doi: 10.1002/bmc.795.

DOI:10.1002/bmc.795
PMID:17340565
Abstract

A simple, rapid and reliable high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of curcumin in rat plasma. Plasma was precipitated with acetonitrile after addition of the internal standard (IS), 4-hydroxybenzophenone. Separation was achieved on a Waters muBondapak C(18) column (3.9 x 300 mm, 5 microm) using acetonitrile (55%) and citric buffer, pH 3.0 (45%) as the mobile phase (flow rate = 1.0 mL/min). The UV detection wavelength was 300 and 428 nm for IS and curcumin, respectively. The extraction efficiencies were 97.08, 95.69 and 94.90% for 50, 200 and 1000 ng/mL of curcumin in rat plasma, respectively. The calibration curve was linear over the range 0.02-1 microg/mL with a correlation coefficient of r(2) > 0.999. The intra- and inter-day coefficients of variation were less than 13%, and mean intra- and inter-day errors were less than +/-6% at 50, 200 and 1000 ng/mL of curcumin. This assay was successfully applied to the pharmacokinetic studies of both solubilized curcumin and its polymeric micellar formulation in rats. It was found that polymeric micelles increased the half-life of curcumin 162-fold that of solubilized curcumin and increased the volume of distribution (Vd(ss)) by 70-fold.

摘要

建立并验证了一种简单、快速且可靠的高效液相色谱(HPLC)法,用于测定大鼠血浆中的姜黄素。加入内标(IS)4-羟基二苯甲酮后,用乙腈沉淀血浆。在Waters muBondapak C(18)柱(3.9×300 mm,5μm)上进行分离,以乙腈(55%)和pH 3.0的柠檬酸缓冲液(45%)作为流动相(流速=1.0 mL/min)。内标和姜黄素的紫外检测波长分别为300和428 nm。大鼠血浆中50、200和1000 ng/mL姜黄素的提取效率分别为97.08%、95.69%和94.90%。校准曲线在0.02 - 1μg/mL范围内呈线性,相关系数r(2)>0.999。在50、200和1000 ng/mL姜黄素水平下,日内和日间变异系数均小于13%,日内和日间平均误差均小于±6%。该方法成功应用于大鼠体内溶解型姜黄素及其聚合物胶束制剂的药代动力学研究。结果发现,聚合物胶束使姜黄素的半衰期比溶解型姜黄素延长了162倍,分布容积(Vd(ss))增加了70倍。

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