摘要
目的:建立测定人体血浆中氟康唑浓度的高效液相色谱法,并对供试制剂与参比制剂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 mL,过柱后用含20%甲醇的水溶液1.0 mL洗涤,再用0.2 mL甲醇洗脱收集,取20 μL进样.色谱柱为C18柱 (150 mm×4.6 mm,5 μm),流动相为0.01 mol·L-1磷酸二氢钾(用磷酸调pH值为5.0)-乙腈(75:25);流速为1.0 mL·min-1,检测波长为267 nm.人体药动学试验采用双周期交叉设计方案,将18例志愿受试者随机分为2组,分别口服氟康唑供试胶囊和参比胶囊150 mg.结果:本方法线性范围为0.1～6.4 mg·L-1,r=0.999 9,最低检测浓度为0.1 mg·L-1,方法回收率为95.7%～108.0%,日内、日间RSD均小于15%,供试制剂与参比制剂主要药动学参数经统计学分析差异无显著性,供试制剂的相对生物利用度为(105.7±12.6)%.结论:本方法灵敏度高,特异性强,重现性好,供试制剂与参比制剂具有生物等效性.
Objective： To compare the pharmacokinetic profiles and bioequivalence of fluconazole capsules by an established HPLC. Methods： An open-label, randomized and crossover dose clinical study recruited 18 male volunteers, who were randomly treated with a single crossover dose of test or reference fluconazole capsules （150 mg each）. The plasma samples （1.0 mL） from the volunteers were loaded on to a C18 cartridges activated with methanol. The cartridge was eluted with 1.0 mL aqueous solutions containing 20 % methanol, and subsequently eluted with 0.2 mL methanol. 20 ttL of the eluate was analyzed by HPLC, which consisted of a Diamonsil ODS C18 column （ 150 mm × 4.6 mm 5μm）, the mobile phase made of 0.01 mol·L^-1 KH2PO4 solution （pH = 5.0, adjusted with H3PO4）-acetonitrile （75：25） with a flow rate of 1.0 mL·min^-1, and detection at 267 nm. Results ： The calibrated linear curve was in the range of 0.1 - 6.4 mg·L^-1 （r=0,999 9）. The detection limit was 0.1 mg·L^-1 and the recovery was 95.7% - 108.0%. The mean within-day and among-day RSD were less than 15%; the P value showed no statistical difference between the test and reference capsules. The relative bioavailability of the test capsules was （105.7 ± 12.6）%. Conclusion： The sensitive, reproducible and specific HPLC confirmed that the test fluconazole capsules were bioequivalent to the reference capsules.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2005年第8期1039-1041,共3页
Chinese Journal of New Drugs
关键词
氟康唑
药动学
高效液相色谱法
固相萃取法
fluconazole
pharmacokinetics
high performance liquid chromatography （ HPLC ）
solid phase extraction
