摘要
目的建立高效液相色谱法测定非洛地平血药浓度；并以市售波依定片为对照，考察单次口服给药后非洛地平缓释片在Beagle犬体内的药物动力学特征，进行生物等效性评价。方法采用标准两阶段2X2交叉实验设计，6条Beagle犬，随机分为2组，分别服用非洛地平缓释片和波依定30mg，于预定的时间点取血样，用高效液相色谱法进行血药浓度测定；采用3P-97药动分析软件，90％可信区间的双单侧t检验法进行生物等效性分析。结果血样以乙醚-正己烷（2：1，V／V）萃取浓缩，提取回收率达到70％；在流动相乙腈-水（65：35，V：V）、检测波长237nm、柠温20℃、流速1．0ml／min色谱条件下，以尼莫地平为内标，血样分离效果好，线性范围3．96～99．0ng／ml血药浓度（r=0．9997）；测得非洛地平缓释片的相对生物利用度为102．7％±14．6％，AUC0-12h、、Cmax、Tmax值的90％的可信区间，均落在参比制剂的80％～125％之间。结论HPLC法测定非洛地平血药浓度方法准确、灵敏；测得非洛地平缓释片与参比制剂波依定生物等效。
Objective To study bioequivalence between the felodipine sustained release tablet （test） and Plendil （reference） by establishing HPLC method to determinate felodipine in dog plasma. Methods The standard two - period 2×2 cross - over design was performed and six dogs were divided randomly into two growps. The plasma concentration of two felodipine formulations was determined by HPLC at scheduled time after a single oral dose （30 rag）. Two one-sided test with 90% confidence interval（ CI ） was taken to evaluate the bioequivalenee by 3P -97 statistical analysis software. Results Extracted with a mixture of ethyl ether and n - hexane （2：1 ） , the recovery of felodipine in plasma samples reached 70%. HPLC method was applied with a C18 column and Nimodipine was selected as internal standard. The mobile phase was ethyl- water （65：25, V： V） with the 1.0 mL/min flow rate at 20℃ temperature. The extracts were separated excellently and detected at 237nm and the linear range of felodipine in plasma was 3.96 -99.0 ng/ml （r =0. 9997）. The relative bioavailability of the test to the reference was 102.7%±14.6% , and the 90% C1 of AUC0-12h、Cmax、Tmax of the test were all between the range of 80%-125% of the reference. Conclusion HPLC The to determine plasma concentration of felodipine was accurate and sensitive. The felodipine sustained release tablet （test） and Plendil （reference） were bioequivalent.
出处
《医学研究杂志》
2008年第10期57-60,共4页
Journal of Medical Research
