Determination of PMEA-Na in dog plasma by liquid chromatography and tandem mass spectrometry and its pharmacokinetic study / 中国临床药理学与治疗学

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 methanolwaterformic acid (25750.5) 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.