Determination of PMEA-Na in dog plasma by liquid chromatography and tandem mass spectrometry and its pharmacokinetic study
- VernacularTitle: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
- Author:
Wenyan WANG
;
Zilong SHEN
;
Shibing WANG
;
Quansheng YAO
- Publication Type:Journal Article
- Keywords:
PMEA-Na;
LC/MS/MS;
plasma concentration;
pharmacokinetics
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2006;11(4):406-409
- CountryChina
- Language:Chinese
-
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 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.
