关键词: PMEA-Na, LC/MS/MS, 血药浓度, 药代动力学

Abstract: 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 withinday 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 t_1/2 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.

Key words: PMEA-Na, LC/MS/MS, plasma concentration, pharmacokinetics