LC-MS/MS法测定可待因在Beagle犬血浆中的质量浓度  

Study on the determination of codeine in Beagle dogs plasma by LC-MS / MS

作　　者：王莉[1] 金艺[1] 李佳阳[1] 杨晓静[1] 袁波[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2013年第11期889-894,共6页Journal of Shenyang Pharmaceutical University

摘　　要：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（150mm×4．6mm，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（multiplereactionmonitoring，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，P-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 spectrom- etry（LC-MS/MS） method for the determination of codeine in dog plasma. Methods Protein precipitation was used for the sample pretreatment with a plasma volume of 200 μL. The chromatographic separation was carded out on an Agela C18 analytical column （150 mm ×4.6 mm,5 μm） and the mobile phase was com- posed of methanol-water-formic acid （V： V： V= 15： 85：0. 5）. Detection was carried out by multiple reaction monitoring. Results The method was linear over the range of 0. 20-20 μg·L^-1 and the lower limit of quanti- fication （LLOQ） was 0. 20 μg·L^-1. The intra-and inter-day precision were within 11.5 % in terms of rela- tive standard deviation （RSD%）. The average recoveries were between 104. 1% - 109.2%. Main pharma- cokinetic parameters were as follows ： t1/2 （ 2. 9 ± 0.5 ） h, Pmax （ 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 ap- plied to pharmacokinetic studies of codeine in Beagle dogs after an oral dose of 13 mg codeine.

关 键 词：可待因 液相色谱-串联质谱 BEAGLE犬 药动学 

分 类 号：R917[医药卫生—药物分析学]