摘要
目的：建立广泛适用、灵敏快速的人血浆中二甲双胍高效液相色谱测定方法,并应用于不同来源制剂的生物利用度研究。方法：血浆样品中加入适量内标,以乙腈沉淀蛋白后用HPLC进行分析。采用Waters XTERRAMS C18色谱柱（5μm,4.6mm×250 mm）,柱温为40℃,优化的流动相组成为乙腈-0.03 mol·L-1磷酸氢二钾-0.02 mol·L-1SDS溶液（33∶29∶38）,流速1.0 mL·min-1,紫外检测器测定波长为234 nm;以两制剂双周期交叉试验设计方法,测定20名自愿受试者口服不同来源的2种二甲双胍片后的药动学参数并进行生物等效性评价。结果：优化方法的线性范围为49.85~2493 ng·mL-1,最低定量限为49.85 ng·mL-1,准确度在91.9%~94.5%之间,日内、日间精密度（RSD）≤8.5%,蛋白沉淀回收率86.4%~93.2%之间,稳定性考察结果良好;实验中,口服给药二甲双胍片受试制剂与参比制剂后,受试者体内药物的Cmax分别为（1234.58±189.11）、（1152.57±238.29）ng·mL-1;Tmax分别为（2.40±0.81）、（2.73±0.85）h;t1/2分别为（4.27±0.86）、（3.92±0.42）h;AUC0-t分别为（8589.85±1649.85）、（7749.71±1303.61）ng·h·mL-1;AUC0-∞分别为（9234.77±1646.80）、（8390.94±1392.35）ng·h·mL-1。以AUC0-t计算,受试制剂盐酸二甲双胍片的相对生物利用度为（112.08±18.38）%;以AUC0-∞计算,受试制剂盐酸二甲双胍片的相对生物利用度为（111.15±16.37）%。结论：优化的方法适用性广,快速灵敏,专属性强,可用于盐酸二甲双胍制剂的临床药动学研究及其制剂的生物等效性评价。不同来源的2种二甲双胍片具有生物等效性。
Objective： To develop a sensitive and rapid high performance liquid chromatographic method for the determination of metformin in human plasma and application to bioavailability study of preparations from different sources. Methods： The protein in plasma samples was precipitated with acetonitrile after addition of internal standard,and then analyzed with an HPLC system. The analytical column was Waters XTERRAMS C18（ 5 μm,4. 6 mm × 250 mm） and the column temperature was 40 ℃. The mobile phase was composed of acetonitrile- 0. 03mol·L- 1dipotassium hydrogen phosphate aqueous solution- 0. 02 mol·L- 1SDS aqueous solution（ 33∶ 29∶ 38）.The flow rate was 1. 0 mL·min- 1. The UV detection wavelength was at 234 nm. The pharmacokinetic parameters and bioequivalence of the two varieties of metformin tablets of different sources after oral administration in 20 volunteers were quantitated and evaluated via a two- preparation,double periodic,cross- over trial. Results： The calibration curve was linear over the concentration range of 49. 85- 2493 ng·mL- 1for metformin. The lower limit of quantification were 49. 85 ng·mL- 1. Inter- and intra- day precisions were less than 8. 5% and accuracy was within 91. 9%- 94. 5%. Protein precipitation recoveries were within 86. 4%- 93. 2% and the analytes were proved to be stable. In this study,for oral administration of test and reference metformin preparations,Cmaxwere（ 1234. 58 ±189. 11） ng·h·mL- 1and（ 1152. 57 ± 238. 29） ng·mL- 1,respectively; Tmaxwere（ 2. 40 ± 0. 81） h and（ 2. 73 ±0. 85） h,respectively; t1 /2were（ 4. 27 ± 0. 86） h and（ 3. 92 ± 0. 42） h,respectively; AUC0- twere（ 8589. 85 ±1649. 85） ng· h · mL- 1and（ 7749. 71 ± 1303. 61） ng · h · mL- 1,respectively; AUC0- ∞were（ 9234. 77 ±1646. 80） ng·h·mL- 1and（ 8390. 94 ± 1392. 35） ng·h·mL- 1,respectively. The relative bioavailability of test metformin hydrochloride preparation was 112. 08% ± 18. 38% calculated by AUC0- t,and 111. 15% ±16. 37% c
出处
《药物分析杂志》
CAS
CSCD
北大核心
2014年第8期1362-1367,共6页
Chinese Journal of Pharmaceutical Analysis
