美他沙酮在Beagle犬体内的药物动力学Pharmacokinetics of metaxalone in Beagle dogs
倪庆纯,魏存芳,杨威,郭琳,肖百全
NI Qing-chun,WEI Cun-fang,YANG Wei,GUO Lin,XIAO Bai-quan(Guangzhou Institute of Pharmaceutical Industry
摘要(Abstract)：
目的建立专属、灵敏、高效的LC/MS/MS法,研究美他沙酮在Beagle犬体内的药物动力学。方法以Zorbax SB-C18为色谱柱,水(含体积分数为0.2%的甲酸)-乙腈(体积比为50:50)为流动相;选用ESI离子源,多反应监测方式进行检测。犬以80 mg.kg-1口服美他沙酮后,采集血浆样品。采用已建立的LC/MS/MS法测定美他沙酮血浆浓度,计算药物动力学参数。结果美他沙酮线性为0.05～10.00 mg.L-1(r=0.997 2)。日内和日间精密度均小于12.2%,准确度均在8.19%之内。美他沙酮口服给药后在Beagle犬体内的主要药物动力学参数如下:t1/2为(4.02±3.04)h,tmax为(1.5±0.35)h,ρmax为(1 402.31±653.96)mg.L-1,AUC(0→24)为(2 735.72±1 264.67)mg.L-1,AUC(0→∞)为(3 109.72±1 283.57)mg.L-1。结论本方法适用于美他沙酮的药物动力学研究。
Objective To establish a liquid chromatography-tandem mass spectrometry method for the determination of metaxalone in Beagle dog plasma.Methods The separation of metaxalone was performed on a ZORBAX SB-C18 column with galantamine as internal standard.The mobile phase consisted of H2O[0.2%(φ)formic acid]and methanol(V∶ V=50∶ 50).Electrospray ionization source was applied and operated in multiple reactions monitoring mode.A series of blood samples were collected after a single dose of 83 mg · kg-1 metaxalone was given to Beagle dogs,plasmas were separated,and the concentrations of metaxalone were determined by LC/MS/MS and the pharmacokinetic parameters were calculated.Results The linear range of metaxalone was 0.05-10.00 mg · L-1(r=0.997 2).Both the inter and intra-day precisions were less than 13% and the accuracy were within 8.19%.The main pharmacokinetic parameters are as follows:t1/2 was(4.02±3.04)h,tmax was(1.5±0.35)h,ρmax was(1 402.31±653.96)mg · L-1,AUC(0→24)was(2 735.72±1 264.67)mg · L-1,AUC(0→∞)was(3 109.72±1 283.57) mg · L-1.Conclusions The method is sensitive,accurate and reliable and suitable for the determination of metaxalone in Beagle dog plasma and its pharmacokinetic study.
关键词(KeyWords)：
美他沙酮;药物动力学;LC/MS/MS;Beagle犬
metaxalone;pharmacokinetics;LC/MS/MS;Beagle dog
基金项目(Foundation): 广东省粤港招标重大项目(2006A35003001)
作者(Author):
倪庆纯,魏存芳,杨威,郭琳,肖百全
NI Qing-chun,WEI Cun-fang,YANG Wei,GUO Lin,XIAO Bai-quan(Guangzhou Institute of Pharmaceutical Industry
DOI: 10.14066/j.cnki.cn21-1349/r.2012.12.016
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