王莉,金艺,李佳阳,杨晓静,袁波
WANG Li,JIN Yi,LI Jia-yang,YANG Xiao-jing,YUAN Bo

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的建立Beagle犬血浆中可待因质量浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法色谱柱为Agela·C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-水-甲酸(体积比为15∶85∶0.5),血浆样品经甲醇沉淀蛋白处理,以多反应监测(multiple reaction monitoring,MRM)扫描方式检测,测定Beagle犬经口给予洛芬待因缓释片后血浆中可待因的质量浓度。结果血浆中可待因质量浓度在0.2~20μg·L-1内线性关系良好,日内和日间精密度RSD≤11.5%,平均提取回收率为104.1%~109.2%,基质效应为119.2%~128.3%。可待因在Beagle犬血浆中主要药动学参数t1/2为(2.9±0.5)h,ρmax为(8.7±3.4)μg·L-1,AUC0-∞为(28.5±7.3)μg·h·L-1。结论该方法适用于可待因在Beagle犬体内药动学的研究。
Objective To develop a simple,rapid and sensitive liquid chromatography-tandem mass spectrometry( LC-MS / MS) method for the determination of codeine in dog plasma. Methods Protein precipitation w as used for the sample pretreatment w ith a plasma volume of 200 μL. The chromatographic separation w as carried out on an Agela C18analytical column( 150 mm × 4. 6 mm,5 μm) and the mobile phase w as composed of methanol-w ater-formic acid( V∶ V∶ V = 15∶ 85∶ 0. 5). Detection w as carried out by multiple reaction monitoring. Results The method w as linear over the range of 0. 20-20 μg·L- 1and the low er limit of quantification( LLOQ) w as 0. 20 μg·L- 1. The intra-and inter-day precision w ere w ithin 11. 5% in terms of relative standard deviation( RSD%). The average recoveries w ere betw een 104. 1%- 109. 2%. Main pharmacokinetic parameters w ere as follow s: t1 /2( 2. 9 ± 0. 5) h,ρmax( 8. 7 ± 3. 4) μg·L- 1,AUC0- ∞( 28. 5 ±7. 3) μg·h·L- 1,respectively. Conclusions This simple and sensitive LC-MS/MS method is successfully applied to pharmacokinetic studies of codeine in Beagle dogs after an oral dose of 13 mg codeine.

关键词(KeyWords)： 可待因;液相色谱-串联质谱;Beagle犬;药动学
codeine;liquid chromatography-tandem mass spectrometry(LC-MS /MS);Beagle dog;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 王莉,金艺,李佳阳,杨晓静,袁波
WANG Li,JIN Yi,LI Jia-yang,YANG Xiao-jing,YUAN Bo

DOI: 10.14066/j.cnki.cn21-1349/r.2013.11.015

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