液质联用测定盐酸哌唑嗪的血药浓度及其片剂的生物等效性研究

 目的建立高效液相色谱-质谱联用方法测定人血浆中盐酸哌唑嗪的浓度,研究盐酸哌唑嗪的人体药动学及生物等效性。方法血浆样品中加入内标盐酸特拉唑嗪后,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。用建立的方法测定18名健康男性志愿者单剂量口服盐酸哌唑嗪试验制剂或参比制剂的体内经-时过程,由血药浓度数据求得各自的药动学参数,双单侧t检验进行生物等效性判定。结果在0.5～100μg·L^-1内呈良好的线性关系,方法回收率为95%～97%,日内、日间RSD均小于10%。单次服用4 mg盐酸哌唑嗪试验制剂或参比制剂后的药动学参数AUC_0→15,AUC_0→∞,ρ_max,t_max,t_1/2分别为(171.62±33.22)和(168.19±23.50)μg·h·L^-1,(177.06±34.16)和(174.40±24.36)μg·h·L^-1,(50.04±16.60)和(47.55±12.23)μg·L^-1,(1.35±0.76)和(1.24±0.75)h,(3.4±1.2)和(3.4±1.1)h。试验制剂对参比制剂的相对生物利用度为(102.3±15.3)%。结论该方法准确、灵敏,无杂质干扰。测得的试验制剂与参比制剂的主要药动学参数之间无明显差异,两种片剂为生物等效制剂。

Determination of Prazosin Hydrochloride in Human Plasma by HPLC-MS: Application to Its Bioequivalance

OBJECTIVE To determine prazosin hydrochloride in human plasma by HPLC-MS method,and to investigate its pharmacokinetics and bioequivalance.METHODS Prazosin hydrochloride concentrations in plasma extracted with methyl tert-butyl ether were determined by HPLC-MS.The selected ion was determined by ESI.The test and reference formulations of prazosin hydrochloride were given to 18 healthy male volunteers.Bioequivalence was determined by two one-sided t-tests.RESULTS The calibration curve was linear within the range of 0.5～100 μg·L^-1,the method recovery was 95%～97%,RSD of intra-day and inter-day were less than 10%.After a single oral dose of 4 mg Prazosin hydrochloride test or reference tablets,the main pharmacokinetic parameters were as follows: AUC_0-15(171.62±33.22) and(68.19±23.50) μg·h·L^-1,AUC_0-∞(177.06±34.16) and(174.40±24.36) μg·h·L^-1,ρ_max(50.04±16.60) and(47.55±12.23)(μg·L^-1),t_max(1.35±0.76) and(1.24±0.75) h,(3.4±1.2) and(3.4±1.1)h,respectively.Relative bioavailability was(102.3±15.3)%.CONCLUSION The method is accurate and sensitive with no endogenous interference.No significant difference exists among the main pharmacokinetic parameters for the test tablets and the reference tablets.The two formulations are bioequivalent.