张文爽,王瀚扬,李颖超,李慧新,姜云霄,张天虹
ZHANG Wenshuang,WANG Hanyang,LI Yingchao,LI Huixin,JIANG Yunxiao,ZHANG Tianhong

• 1:沈阳药科大学药学院
• 2:本溪市高级中学

摘要(Abstract)：

目的建立测定大鼠血浆中熊果酸质量浓度的UPLC-MS/MS法,并将其用于熊果酸原料药和熊果酸磷脂复合物在大鼠体内的药动学研究。方法采用液液萃取法处理血浆样品,以甘草次酸为内标物质(IS),采用Phenomenex C18(50 mm×2.1 mm,1.6μm)色谱柱,流动相为甲醇-水(10 mmol·L-1乙酸铵)(体积比80∶20),流速为0.2 m L·min-1,离子源为电喷雾电离源,以负离子扫描选择离子监测模式进行检测。结果血浆中熊果酸在0.50~250.0μg·L-1内线性关系良好,定量下限为0.50μg·L-1,日内和日间精密度RSD在4.1%~9.3%内,准确度在0.78%~1.5%内,提取回收率在87.8%~104.1%内,基质效应在87.2%~105.0%内。结论该方法符合生物样品分析方法指导原则要求,适用于熊果酸原料药及熊果酸磷脂复合物在大鼠体内的药动学研究。
Objective To develop an UPLC-MS/MS method for determination of ursolic acid in rat plasma,and apply it in the pharmacokinetic study. Methods The plasma samples w ere pretreated by liquid-liquid extraction w ith methyl tert-butyl ether and an UPLC-MS/MS method w as performed ona Phenomenex C18( 50 mm × 2. 1 mm,1. 6 μm) column. The mobile phase was consisted of methanol and 10 mmol·L-1 ammonium acetate( V ∶ V = 80∶ 20) w ith the flow rate of 0. 2 m L·min-1. The selected ion monitoring( SIM)w as performed at m/z 455. 3 for ursolic acid and m/z 469. 3 for glycyrrhetinic acid( internal standard,IS) in negative ion mode w ith electrospray ionization( ESI) source. Results The assay show ed good linearity in the range of 0. 50-250. 0 μg·L-1 for ursolic acid w ith the low er limit of quantitation at 0. 50 μg·L-1. The mean intra-day and inter-day precisions w ere betw een 4. 1% and 9. 3%,and the accuracy w as betw een0. 78% and 1. 5%. The extraction recovery w as betw een 87. 8% and 104. 1%,and the matrix effect ranged from 87. 2% to 105. 0%. Ursolic acid plasma samples w ere stable during the analysis and the storage period. Conclusions The validated method is in accordance w ith the analytical method guidelines and can be applied in the pharmacokinetic study of ursolic acid.

关键词(KeyWords)： 熊果酸;磷脂复合物;UPLC-MS/MS;药动学
ursolic acid;phospholipid complex;UPLC-MS/MS;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 张文爽,王瀚扬,李颖超,李慧新,姜云霄,张天虹
ZHANG Wenshuang,WANG Hanyang,LI Yingchao,LI Huixin,JIANG Yunxiao,ZHANG Tianhong

DOI: 10.14066/j.cnki.cn21-1349/r.2018.01.006

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