摘要
目的建立人体血浆中氟康唑浓度的HPLC-M S测定方法,评价氟康唑胶囊在健康人体内的药动学及生物等效性。方法以甲硝唑为内标,血浆样品用甲醇直接沉淀去除蛋白,采用HPLC-M S法,测定20名健康受试者随机双交叉口服150m g氟康唑受试胶囊或参比胶囊后不同时间点的血药浓度,计算其主要药动学参数及相对生物利用度,评价两种制剂的生物等效性。结果氟康唑受试胶囊和参比胶囊的主要药动学参数分别为:AUC0-120(121.59±12.79)、(115.01±13.44)μg.h.mL-1;Cm ax(3.09±0.29)、(3.18±0.33)μg.h.mL-1;Tm ax(2.6±1.1)、(2.3±1.0)h、t1/2(31.67±4.33)、(30.99±4.95)h。以AUC0-120计算的受试胶囊的相对生物利用度为(106.4±11.8)%。结论该测定方法灵敏、准确、简便、快速;2种制剂具有生物等效性。
OBJECTIVE To establish a high performance liquid chromatography-electrospray mass spectrometry method for the determination of fluconazole in human plasma and to study the pharmacokinetics and bioequivalence of fluconazole in healthy volunteers. METHODS After being deproteined by methanol the fluconazole concentration in plasma was determined by HPLC-MS method with metronidazole for the internal standard. A randomized crossover design was performed in 20 healthy volunteer. In the study periods, a single 150 mg dose of each capsule was administered to each volunteer. The main pharmacokinetic parameters and relative bioavailability were calculated to evaluate the bioequivalence of 2 preparations. RESULTS AUC0-120 of tested fluconazole capsule and reference fluconazole capsule were （121.59±12.79）and （115.01±13.44）μg · h · mL^-1,Cmaxwere （3.09±0. 29） and （3. 18±0. 33）μg · h · mL^-1,Tmaxwere （2.6±1.1） and （2.3±1.0）h,t1/2 were （31.67 ± 4.33） and （30.99 ± 4.95） h, respectively, and the relative bioavalability of the test capsule was （106.4±11.8） %. The main pharmacokinetic parameters obtained showed no statistically significant difference between 2 products. CONCLUSION The assay is proved to be sensitive,accurate,and convenient. The reference and test formulation are bioequivalent.
出处
《海峡药学》
2005年第6期155-158,共4页
Strait Pharmaceutical Journal
