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

作　　者：王志强[1] 胡卢丰[1] 曹高忠[1] 张梅君[1] 吴继禹[1] 傅红兴[2] 

机构地区：[1]温州医学院附属第一医院药剂科,温州325000 [2]温州医学院药学院药剂学教研室,温州325035

出　　处：《中国临床药学杂志》2012年第6期340-343,共4页Chinese Journal of Clinical Pharmacy

基　　金：温州市科技局课题基金(编号Y20090087)

摘　　要：目的建立用于测定犬血浆中盐酸二甲双胍浓度的LC-MS/MS方法 ,比较3种盐酸二甲双胍制剂在Beagle犬体内药动学参数之间的差别。方法 6只Beagle犬,单剂量三周期分别口服3个剂型药物,按规定时间点取血样,血浆样品经乙腈沉淀蛋白,取上清液直接进行LC-MS/MS测定,以Zorbax SB-C_(18)(150 mm×2.1 mm,5μn)为色谱柱,V(乙腈):V(0.1%甲酸水溶液)=40:60为流动相,流速0.3 mL·min^(-1),柱温30℃,检测波长233 nm,并计算主要药动学参数。结果盐酸二甲双胍质量浓度在0.05～5 mg·L^(-1)内线性关系良好,回归方程为:y=0.686 8x-0.022 2(r=0.999 5),平均回收率为103.2%;盐酸二甲双胍普通片、盐酸二甲双胍缓释片和盐酸二甲双胍胃滞留片的主要药动学参数AUC_(0→t)分别为(97.01±5.36)、(134.6±10.2)、(204.0±19.2)mg·h·L^(-1),t_(max)分别为(2.612±1.35)、(5.869±0.95)、(7.105±1.33)h。结论将盐酸二甲双胍制成胃滞留缓释片可显著提高生物利用度;用LC-MS/MS法测定犬血中盐酸二甲双胍浓度,方法简单、快捷、灵敏、准确,适用于临床药动学及药效学的研究。AIM To develop a method for the determination of mefformin hydrochloride in Beagle dog plasma and to study its pahrmacokinetics of three kinds of meffonnin hydrochloride preparations. METHODS Six Beagle dogs were taken three kinds of meffomain hydrochloride preparations according to experiment design and the blood was drown 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, 5μm） at the flow rate of 0.3 mL· min^-1 and 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 mefformin 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： AUC0→t were （97.01 ± 5.36） ,（134.6 ± 10.2） and （204.0 ± 19.2） mg·h·L^-1, tm,xWere （2.612 ± 1.35）, （5.869 ± 0.95） and （7. 105 ±1.33） h. CONCLUSION The relative bioavailability of metformin hydroehloride 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 pharmacokineties and pharmacodynamies of meffomain hydroehloride.

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 

分 类 号：R96[医药卫生—药理学]