PMEA-Na在beagle犬血浆中的液相色谱/质谱/质谱联用法测定及其药代动力学(英文)

Determination of PMEA-Na in dog plasma by liquid chromatography and tandem mass spectrometry and its pharmacokinetic study

目的：建立LC/MS/MS法测定犬血浆中PMEA-Na浓度,进行其药代动力学研究.方法：血浆样品经甲醇沉淀蛋白后,采用多反应监测法测定其血药浓度.色谱柱为Xterra MS柱,流动相为甲醇：水：甲酸（25：75：0.5）,流速为 0.25 ml·min^-1.Beagle犬分3个剂量组经静脉给药,给药剂量分别为 1.0、3.0 和 6.0 mg·kg^-1.药代动力学参数通过DAS软件计算获得.结果：PMEA-Na线性范围：0.02～20 mg·L^-1 （r=0.999）;最低检测浓度为 20 μg·L^-1,方法回收率为 97.1%～107.3%,日内日间变异分别小于 6.5%、10.8%.beagle 犬在 1.0, 3.0 与 6.0 mg·kg^-1剂量下单次iv PMEA-Na后,测得其AUC分别为 2.3±0.5, 8.2±1.3 and 18.5±1.3 mg·L^-1·h; t1/2 为 3.9±1.8, 8.4±1.5 and 8.9±0.6 h; CL为 0.44±0.09, 0.35±0.05 and 0.31±0.03 ml·h^-1·kg^-1.结论：本方法专属性强,准确性好,可用于PMEA-Na血药浓度测定和药代动力学研究.

AIM： To established an HPLC/MS/MS method for the study of pharmcokinetics of PMEA-Na （the mono-sodium salts of 9-[2-（phosphonomethoxy） ethyl] adenine） in beagle dogs. METHODS： PMEA-Na and internal standard 9-（3-phosphony-methoxypropyl） adenine were isolated from plasma by protein precipitation with methanol, and then analyzed adopting multiple reaction monitoring （MRM） mode. Using Xterra MS column, the mobile phases consisted of methanol：water：formic acid （25：75：0.5） at a flow rate of 0.25 ml·min^-1. Beagle dogs received the intravenous dosage of PMEA-Na at 1.0, 3.0 and 6.0 mg·kg^-1. Pharmacokinetic parameters were obtained from concentration-time curves by non-linear least-squares regression using the program DAS. RESULTS： The linear calibration curve was obtained in the concentration range of 0.02 to 20 mg·L^-1 （r=0.999）, and the limit of quantitition was 20 μg·L^-1. The within-day and internal-day precisions （RSD） were less than 6.5% and 10.8%, respectively. The accuracy was 97.1%～107.3%. After a single dose studies in dogs the AUC were 2.3±0.5, 8.2±1.3 and 18.5±1.3 mg·L^-1·h; the t1/2 were 3.9±1.8, 8.4±1.5 and 8.9±0.6 h; the CL were 0.44±0.09, 0.35±0.05 and 0.31±0.03 ml·h^-1·kg^-1 at the dose level of 1.0, 3.0 and 6.0 mg·kg^-1 respectively. CONCLUSION： The analytical method is sensitive and specific for investigation the pharmacokintics of PMEA-Na in beagle dogs.