美他沙酮在Beagle犬体内的药物动力学

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。

Pharmacokinetic of metaxalone in Beagle dogs

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 : t_1/2 was (4.02±3.04) h,t_max was (1.50±0.35) h,ρ_max 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.