论文部分内容阅读
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 establish a LC-MS / MS method for the determination of guanfacine in Beagle dogs plasma and to study the pharmacokinetics of guanfacine sustained-release tablets in Beagle dogs. Methods The mobile phase consisted of Acetonitrile - water - formic acid (volume ratio 20.0:80.0:0.01) with Agela C8 column (50 mm × 2.1 mm, 3 μm) Scanning method was tested to determine the dog oral administration of guanidine hydrochloride sustained-release tablets after plasma drug quality concentration. Results The plasma concentrations of guanfafusine in Beagle dogs were linear within the range of 0.05-20.0 μg · L-1, with a correlation coefficient of 0.9992. The RSD of intra- and inter-day precision was ≤9.0%. The average guanfacine extraction The recoveries ranged from 94.7% to 100.9%. The matrix effects of guanfacine were within 99.9% -107.5%. The main pharmacokinetic parameters of guanfacine in dogs were as follows: t1 / 2 was (3.5 ± 1.3) h, ρmax (3.72 ± 1.37) μg · L-1, tMR 0-24 was (4.9 ± 1.6) h, tMR 0-∞ was (12.2 ± 11.4) h and AUC0-24 was (18.80 ± 4.81) μg · h · L -1, and the AUC0-∞ was (21.63 ± 4.76) μg · h · L-1. Conclusion The method is rapid, simple and sensitive and is suitable for the pharmacokinetic study of guanfacine in Beagle dogs.