LC-MS/MS法测定Beagle犬血浆中胍法辛的质量浓度

Determination of guanfacine in Beagle dogs plasma by LC-MS/MS

目的建立液质联用（LC-MS/MS）方法测定Beagle犬血浆中胍法辛的药物质量浓度,从而研究胍法辛缓释片在Beagle犬体内的药动学特征。方法色谱柱为Agela C8柱（50 mm×2.1 mm,3μm）,流动相为乙腈-水-甲酸（体积比20.0∶80.0∶0.01）,采用液-液萃取法,以多反应离子监测（MRM）扫描方式进行检测,测定犬经口给予盐酸胍法辛缓释片后血浆中的药物质量浓度。结果Beagle犬血浆中胍法辛的药物质量浓度在0.05～20.0μg·L-1内线性关系良好,相关系数r=0.9992;日内和日间精密度的RSD≤9.0%;胍法辛的平均提取回收率在94.7%～100.9%内;胍法辛的基质效应在99.9%～107.5%内;胍法辛在犬血浆中主要药动学参数如下：t1/2为（3.5±1.3）h,ρmax为（3.72±1.37）μg·L-1,tMR 0-24为（4.9±1.6）h,tMR 0-∞为（12.2±11.4）h,AUC0-24为（18.80±4.81）μg·h·L-1,AUC0-∞为（21.63±4.76）μg·h·L-1。结论该方法快速、简便、灵敏,适用于胍法辛在Beagle犬体内的药物动力学研究。

Objective To develop a rapid and sensitive liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the determination of guanfacine in Beagle plasma, and study the pharmacokinetics characteristic of guanfacine in Beagles plasma. Methods The chromatographic separation was accomplished on Agela C8 analytical column（ 50 mm× 2.1 mm,3 μm）using a mobile phase consisting of acetonitrile-wa- ter-formic acid（ V： V： V = 20.0： 80.0： 0. 01 ） at a flow rate of 0. 3 mL. min -1. Liquid-liquid extraction was used for the sample pretreatment. The plasma concentration of guanfacine was detected by multiple reactions monitoring after the Beagle dogs were given guanfacine extended-release. Results A good linear calibration curve of guanfacine was obtained over the concentration range of 0. 05- 20.0 μg·L^-1, r = 0. 999 2 ; The in- tra-and inter-day precision was both less than 9.0%. The average recoveries were between 94. 7% and 100.9%. The matrix effects were between 99.9% and 107.5%. The main pharmacokinetics parameters were as follows：t1/2 （3.5 ±1. 3） h,Pmax （3.72 ±1.37） μg·h- L^- 1,tMR0-24（4.9± 1.6）h,tMR0-∞ （12.2 ± 11.4）h, AUC0- 24 （ 18.80 ± 4. 81 ） μg·h- L^- 1, AUC0-∞ （ 21.63± 4.76 ） μg·h- L^- 1, respectively. Conelusions This simple and sensitive LC-MS/MS method is successfully applied to the pharmacokinetics studies of guan- facine in Beagle dogs＇ plasma.