两种格列吡嗪胶囊的人体生物等效性研究

Bioeguivalent Study of Two Glipizide Capsules in Human Plasma

目的建立测定人血浆中格列吡嗪浓度的高效液相色谱法,并对供试制剂格列吡嗪胶囊与参比制剂格列吡嗪胶囊的生物等效性进行评价.方法血样处理采用固相萃取方法,萃取小柱用甲醇活化后加入血浆1.0 mL,过柱后用含20%甲醇的水溶液1.0 mL洗涤,弃去洗涤液,再用1.0 mL甲醇洗脱收集,收集液于60 ℃水浴挥干,最后用100 μL甲醇溶解,取20 μL进样.色谱条件:色谱柱为ODS C18柱(5 μm,4.6 mm×150 mm );流动相为纯化水(用冰醋酸调pH值为3.65)-乙腈(51 ∶49);流速为1.0 mL·min-1;紫外检测波长为275 nm.人体药动学试验采用双周期交叉设计方案,将18名志愿受试者随机平均分成两组,分别口服格列吡嗪供试胶囊和参比胶囊10 mg.结果格列吡嗪的线性范围为20～960 ng·mL-1,r＝0.999 9,最低检测限为20 ng·mL-1,方法回收率为98.2%～105.7%,日内、日间RSD均＜10%,供试制剂与参比制剂格列吡嗪胶囊的主要药动学参数差异无显著性.结论该方法灵敏度高,特异性强,重现性好.供试与参比制剂格列吡嗪胶囊具有生物等效性.

Objective To establish a HPLC method for the determination of two glipizides and their bioequivalence in male volunteers. Method 1.0 mL serum sample was added to C18 cartridges, and then washed with 1.0 mL 20% methanol solution. The cartridge was eluted with methanol. The residue from the eluate evaporated to dryness at 60 ℃ was dissolved in methanol and injected into a Diamonsil ODS column （4.6 mm× 150 mm, 5 μm）. The mobile phase was purified water （pH value = 3.65, adjusted with acetic acid）-acetonitrile （51 ： 49）, the flow rate 1.0 ng·min^-1, and the detect wavelength 275 nm. A single oral dose of 10 mg of test capsule or reference capsule was given to 18 volunteers in randomized in two groups with crossover design. Results The linear range was within 20 - 960 ng·mL^-1 , r = 0. 999 9. The limit of detection was 20 ng·mL^-1. The recovery rate was 98.2% - 105.7%. Their within-day precision RSD and between-day precision RSD were less than 10%. The main pharmacokinetic parameters had no significant difference between two preparations. Conclusion This method is sensitive, specific and suitable for the determination of glipizide concentration in human plasma. The two preparations are bioequivalent.