HPLC-MS/MS研究国产磷酸奥司他韦胶囊在健康人体的生物等效性

 目的 建立测定血浆中国产磷酸奥司他韦胶囊（商品名：军科奥韦胶囊）活性代谢产物浓度的LC-MS/MS方法，研究军科奥韦胶囊在中国健康男性志愿者的主要药动学参数以及与参比制剂的生物等效性。方法 采用2制剂双周期交叉试验设计，24名受试者分别单剂量口服受试制剂军科奥韦胶囊和达菲参比制剂，用LC-MS/MS测定其活性代谢产物的含量，所得参数经BAPP2.0软件计算药动学参数并考察生物等效性。结果 口服参比制剂及受试制剂后，其活性代谢产物的ρ_max分别为（625.17±147.76）和（633.57±115.28）μg·L^-1；t_max分别为（4.5±1.0）和（4.5±1.2）h；t_1/2分别为（8.13±1.13）和（7.79±0.89）h；MRT分别为（12.09±1.38）和（11.95±1.03）h; AUC_0-τ分别为（7 247.02±1 720.33）和（7 506.16±1 454.36）μg·h·L^-1；AUC_0-∞分别为（7 428.75±1 793.94）和（7 659.99±1 477.83）μg·h·L^-1；受试制剂对参比制剂的相对生物利用度为（105.8±17.7）%。结论 利用方差分析及双单侧t检验分别对受试和参比制剂进行生物等效性评价，军科奥韦胶囊和已上市的达菲胶囊制剂具有生物等效性。

Bioavailability and Bioequivalence of Oseltamivir in Chinese Health Volunteers Using the HPLC-MS/MS Method

OBJECTIVE To determine four phenolic acids (procatechualdehyde, rosmarinic acid , lithospermic acid, salvianolic acid B) in rat plasma after oral administration of salvianolic acids and Panax notoginseng saponins (5∶1), and to evaluate its pharmacokinetics. METHODS A high-performance liquid chromatography (HPLC) method was established for the simultaneous determination of four phenolic acids. Chromatographic separation was achieved on a Zorbax SB-C₁₈ column (4.6 mm×250 mm, 5 μm) at 30 ℃, with a linear gradient elution of acetonitrile and 0.026% aqueous phosphoricacid (v/v), at the flow rate of 1 mL·min^-1. The eluent was detected at 280 nm for the four phenolic acids and internal standard. The plasma sample was extracted with ethyl acetate twice after acidification by 10% hydrochloric acid. The pharmacokinetic parameters were obtained. RESULTS The within- and between-day variation for the four phenolic acids in plasma were below 15% and the extraction recovery was above 70%. The pharmacokinetic parameters for the four phenolic acids were as followes t_max, ρ_max and AUC_0-∞ were 10.0 min, 6.466 mg·L^-1 and 82.1 mg·min·L^-1 for procatechualdehyde; 11.7 min, 10.50 mg·L^-1 and 564.8 mg·min·L^-1 for rosmarinic acid, respectively; 20.8 min, 5.950 mg·L^-1 and 1 123 mg·min·L^-1 for lithospermic acid respectively; 8.3 min, 48.12 mg·L^-1 and 4 026 mg·min·L^-1 for salvianolic acid B. CONCLUSION The method is simple, rapid and sensitive for the determination of four compounds in rat plasma and the study of pharmacokinetics.