LC-ESI-MS法测定人血浆非那雄胺的浓度及其药动学(英文)

Determination of finasteride in human plasma and its pharmacokinetics and relative bioavailability by HPLC-electrospray mass spectrometry

目的：建立液质联用方法测定人血浆中非那雄胺的浓度。方法：采用自身对照交叉给药方式,单剂量分别给予20名男性健康志愿者2种非那雄胺片2 mg,用乙酸乙酯提取血浆中非那雄胺后由C_(18)柱分离,质谱检测器测定。结果：该法线性范围为0．3～50μg·L^(-1)(r=0．9992),方法回收率在98．39%～104．76%之间,日内和日间精密度都小于10%。其主要药动学参数c_(max)为(22±4)和(22±5)μg·L^(-1),AUC_(0～24)为(125±27)和(127±30)μg·h·L^(-1),t_(1/2)为(4．4±0．6)和(4．5±0．5)h；t_(max)为(3．0±0．7)和(2．8±0．9)h。结论：2种制剂间的主要动力学参数无明显差异,为生物等效制剂,其相对生物利用度为(99．3±9．2)%。

AIM： A new HPLC-MS method was developed to determine finasteride in human plasma. METHODS： Two formulations of finasteride tablets were given to 20 healthy male volunteers according to a randomized 2-way cross-over design. The samples were extracted by ethyl acetate under basic conditions, then were separated by C18 column and determined by mass detector. RESULTS： The calibration curve of finasteride was linear within the range of 0.3-50μg·L^-1, with r = 0.999 2. The recovery of this method was within 98.39 %-104.76 %, and intra-day and inter-day RSD were less than 10 %. The pharmacokinetics parameters of the two formulations were （22 ± 4） and （22 ±5） Ixg.L-1 for cmax; （125 ± 27） and （127 ± 30） μg·h·L^-1 for A UC0-24; （4.4 ±. 0.6） and （4.5 ± 0.5） h for t1/2; （3.0 ± 0.7） and （2.8 ± 0.9） h for tmax, respectively. The results indicated that there was no significant difference on cmax, A UC0-24, t1/2 or tmax values between the two formulations. CONCLUTION ： The relative bioavailability of tablets I with respect to tablets II is （99.3 ± 9.2） % by the A UC0-24 measurement, and bioe quivalence is observed between the two tablets.