摘要
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 detemination of metaxalone in beagle plasma. Methods The separation of metaxalone was performaed on a ZORBAX SB-C18 column with galantamine as internal standard. The mobile phase was composed by H2O[0.2%（φ）formic acid] and methanol （V：V=50：50）. Electrospray ionization source was applied and operated in multiple reaction monitoring mode. A series of blood samples were collected after a single dose of 83 mg＆#8226;kg-1 metaxalone was given to beagle dogs, plasma was separated, and the concentration of metaxalone was detemined by LC/MS/MS and the pharmacokinetic parameters were calculated. Results The linear range of metaxalone was 0.05-10.00 mg＆#8226;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 （1.50±0.35） h,ρmax was （1 402.31±653.96） mg＆#8226;L-1, AUC（0→24） was （2 735.72±1 264.67） mg＆#8226;L-1,AUC（0→∞） was （3 109.72±1 283.57）＆#61472; mg＆#8226;L-1. Conclusions The method is sensitive, accurate and reliable and suitable for the detemination of metaxalone in beagle plasma and its pharmacokinetic study.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2012年第12期963-966,共4页
Journal of Shenyang Pharmaceutical University
基金
广东省粤港招标重大项目(2006A35003001)
