UPLC-MS/MS法测定人血浆中非那雄胺浓度及2种片剂的生物等效性研究  

Determination of plasma concentration by UPLC-MS/MS and bioequivalence of two finasteride preparations in human

作　　者：王鸿芡 王曼 罗柱[3] 秦永平[3] 南峰[3] 向谨[3] 舒世清[3] 朱晓红[3] 梁茂植[3] 余勤[3] 叶利明[1] 

机构地区：[1]四川大学华西药学院,成都610041 [2]成都中医药大学药学院,成都610075 [3]四川大学华西医院临床药理研究室,成都610041

出　　处：《中国新药杂志》2018年第4期437-442,共6页Chinese Journal of New Drugs

摘　　要：目的:建立UPLC-MS/MS法测定人血浆中非那雄胺的浓度,并用于非那雄胺片在中国健康男性受试者的生物等效性研究。方法:采用单中心、开放、单剂、双周期、随机、自身交叉设计,28例健康男性受试者口服1 mg非那雄胺片试验制剂或参比制剂分别进行空腹和餐后试验。采用UPLC-MS/MS法测定人血浆中的非那雄胺浓度;Win Non Lin 6.4软件,非房室模型法计算药动学参数,并进行生物等效性的判断。结果:非那雄胺在0.05~40 ng·m L-1线性良好,准确度、精密度、基质效应、回收率和稳定性符合相关要求。2种给药条件下,试验制剂AUC0~t,AUC0~∞和Cmax的90%置信区间均在参比制剂相应参数的80%~125%,2种制剂Tmax间的差异均无统计学意义(P>0.05)。结论:该方法能快速、准确测定非那雄胺在人血浆中的浓度,2种片剂生物等效。Objective： To establish a UPLC-MS/MS method for determination of the concentration of finasteride in human plasma,and evaluate the bioequivalence of finasteride in healthy Chinese male volunteers.Methods： In a single-center,open,single-dose,double cycle,random and self-crossover design test,28 healthy male volunteers received 1 mg reference or test finasteride tablet orally under fasting and fed conditions. Drug concentrations in plasma were determined by a UPLC-MS/MS method. The pharmacokinetic parameters of finasteride were calculated with noncompartmental analysis method using Win Non Lin 6. 4,and bioequivalence was assessed.Results： The standard curves were found to be linear in the range of 0. 05 - 40 ng·m L^-1. The 90% CI of AUC0 ~ t,AUC0 ~ ∞and Cmaxbetween the test and reference preparations were within the limits of 80% - 125% under fasting and fed conditions,respectively,and the Tmaxwere not significantly different（ P 〉0. 05）. Conclusion： This method was proved to be rapid and accurate for the bioequivalence test of finasteride. The test and reference tablets are bioequivalent.

关 键 词：非那雄胺 超高效液相色谱串联质谱法 血药浓度 生物等效性研究 

分 类 号：R969.1[医药卫生—药理学]