中国临床药学杂志2012,Vol.21Issue(6):340-343,4.
LC-MS/MS法测定盐酸二甲双胍犬血浆浓度及3种盐酸二甲双胍制剂在犬体内的药动学分析
Determination of three kinds of metformin hydrochloride preparations in Beagle dog plasma by LC-MS/MS and study on its pharmacokinetics
摘要
Abstract
AIM To develop a method for the determination of metformin hydrochloride in Beagle dog plasma and to study its pahrmacokinetics of three kinds of metformin hydrochloride preparations. METHODS Six Beagle dogs were taken three kinds of metformin hydrochloride preparations according to experiment design and the blood was drawn at the specified time. After being deproteinized with acetonitrile, the supernatant of plasma samples was injected into LC-MS/ MS system, then separated on a Zorbax SB- C18 column(150 mm× 2.1 mm,5 μm)at the flow rate of 0.3 mL·min-1and detected at the wavelength of 233 nm. The mobile phase was V(acetonitrile): V(0.1% methanoic acid) =40 : 60 and the column temperature was 30 ℃. The main pharmacokinetic parameters were calculated. RESULTS A good linearity was obtained from 0.05 to 5 mg·L-1 plasma concentration of metformin hydrochloride. The regression equation was y = 0.686 8x -0.022 2(r = 0.999 5). The mean recovery was 103.2% .The main pharmacokinetic parameters of common tablets, sustained-release tablets and gastroretentive sustained-release tablets were as follows: AUCo→t were (97.01 ± 5.36), (134.6± 10.2) and (204.0 ±19.2) mg·h·L-1, tmaxwere (2.612± 1.35),(5.869 ±0.95) and (7.105±1.33)h. CONCLUSION The relative bioavailability of metformin hydiochloride gastroretentive sustained-release tablets is obvious better than that of the other two preparations. The method is simple, rapid, accurate and suitable for being applied to study pharmacokinetics and pharmacodynamics of metformin hydrochloride.关键词
盐酸二甲双胍/高效液相色谱-质谱联用法/药动学/Beagle犬Key words
metformin hydrochloride/ LC-MS/MS/ pharmacokinetics/ Beagle dog引用本文复制引用
王志强,胡卢丰,曹高忠,张梅君,吴继禹,傅红兴..LC-MS/MS法测定盐酸二甲双胍犬血浆浓度及3种盐酸二甲双胍制剂在犬体内的药动学分析[J].中国临床药学杂志,2012,21(6):340-343,4.基金项目
温州市科技局课题基金(编号 Y20090087) (编号 Y20090087)