中国临床药理学与治疗学2012,Vol.17Issue(2):199-205,7.
LC-MS/MS法测定犬体内托拉塞米浓度及相对生物利用度研究
LC-MS/MS determination of torasemide in Beagle dog plasma and bioavailabilitv evaluation
摘要
Abstract
AIM- To establish an LC-MS/MS method for the determination of torasemide in Beagle dog plasma, and study the relative bio-availability of the torasemide sustained release tablets. METHODS: A reversed phase HPLC column of Waters Symmetry-C18 (100 mm× 4. 6 mm, 5 μm) was used in the experiment. Aceto-nitrile-20 mmol/L ammonium formate (65 : 35, V/V) was used as mobile phase at the flow rate of 0. 4 mL/min, the column temperature was set at 30 ℃. A single oral dose of 5 mg torasemide release tablets or reference tablets were given to 6 Beagle dogs in an open randomized two way crossover design. The concentrations of plasma samples collected at the different time were determined by LC-MS/MS method. RESULTS-With the linear range of 0. 02 -5 μg/mL and the lower limit quantification of 0.02 μg/mL, the LC-MS/MS method had high sensitivity, stabili-ty and specificity. The main pharmacokinetic parameters of test sustained release tablets and reference tablets were as follows: the Cmax were (2.6 + 0.5) fig/mL and (3.0 + 0.6) g/mL,the tmax were (3. 3 ±1.4) h and (1.2 + 0.8) h,the AUC0-48h were (36.1 + 11.0) μg · h · mL-1 and (32. 1±13. 1) (μg · h · mL-1. Compared to regular tablets, the bioavailability of sustained release tablets was (118.0 + 28.3)%. CONCLUSION: The method is simple, accurate and robust for the determination of torasemide in Beagle dog plasma, and successfully applied it to the bioavailability evaluation of torasemide sustained release tablets given to Beagle dogs.关键词
托拉塞米/LC-MS/MS/相对生物利用度Key words
Torasemide/ LC-MS/ MS/.Rela- tive bioavailability分类
医药卫生引用本文复制引用
李瑞兴,樊慧蓉,魏广力,任晓文,司端运,刘昌孝..LC-MS/MS法测定犬体内托拉塞米浓度及相对生物利用度研究[J].中国临床药理学与治疗学,2012,17(2):199-205,7.基金项目
国家973项目(2010CB735602) (2010CB735602)