高效液相色谱-质谱法测定人体中瑞波西汀的药动学和生物利用度

Pharmacokinetics and bioavailability of reboxetine in healthy human volunteers using HPLC-MS

目的：建立人血浆中瑞波西汀的高效液相色谱-质谱测定方法,用于研究瑞波西汀的人体药动学及相对生物利用度。方法：血浆经叔丁基甲醚提取,采用高效液相色谱-质谱法,电喷雾电离源选择性正离子峰检测。测定20名健康男性志愿者单剂量口服瑞波西汀实验制剂或参比制剂的体内经时过程,由血药浓度数据获得各自的药动学参数,以双单侧t检验进行生物等效性判定。结果：在2．0～280．0μg．L^(-1)范围内呈良好的线性关系,r=0．9999,平均回收率为93．2%～102．4%,日内RSD≤6．6%,日间RSD≤6．3%。单次服用8mg瑞波西汀实验制剂或参比制剂后的主要药动学参数AUC_(0～60),c_(max),t_(max),t_(1/2)分别为(2926±s792)和(2937±803)μg·h·L^(-1),(202±41)和(208±47)μg·L^(-1),(1．8±0．7)和(2．1±0．8)h,(15±4)和(15±4)h。相对生物利用度为(100±12)%。结论：该方法灵敏度高,无杂质干扰,结果准确。测得的实验制剂与参比制剂的主要药动学参数之间无明显差异,为生物等效制剂。

AIM： To determine reboxetine in human plasma by HPLC-MS method and investigate its pharmacokinetic parameter and bioavailability. METHODS： The reboxetine concentrations in plasma extracted with methyl-t-butyl ether extraction were determined by HPLC-MS; using zaleplon as internal standard. The selected ion was determined by ESI±. The test and reference formulations of reboxetine were given to 20 healthy male volunteers. Bioequivalence was determined by two one-sided t-tests. RESULTS： The calibration curve was linear within the range of 2.0-280.0μg·L^-1 with coefficient correlation r = 0.999 9. The average recovery rate was 93.2 %-102.4 %, and RSD of intra-day and inter-day were no more than 6.6 % and 6.3 %, respectively. After a single oral dose of 8 mg, the main pharmacokinetic parameters of reboxetine, AUC0-60, cmax, tmax,t1/2 were （2 926 ± 792） and （2 937 ± 803）μg·h·L6-1, （202 ± 41） and （208 ± 47）μg·L^-1, （1.8 ± 0.7） and （2.1 ± 0.8） h, （15 ± 4） and （15 ± 4） h, respectively. Relative bioavailability was （100 ± 12） %. CONCLUSION： The method is accurate and sensitive, without endogenous interference. No significant difference exists in the main pharmacokinetic parameters between the test tablets and the reference. The two formulations are bioequivalent.