人血浆中左炔诺孕酮的液相色谱-质谱联用测定法及生物等效性应用

目的:建立快速、灵敏的液相色谱-质谱联用(LC-MS)法测定人血浆中左炔诺孕酮的浓度,并应用于制剂的生物等效性研究。方法:20名健康志愿者随机双交叉单剂量口服左炔诺孕酮参比及受试制剂1．5 mg,血浆样品经液-液萃取法处理后,进行LC-MS测定。结果:参比制剂和受试制剂中药物的主要药动学参数如下:t_(1/2)分别为(11．2±s 2．4)和(12±3)h,c_(max)分别为(9±4)和(10±5)μg·L~(-1),t_(max)分别为(2．5±0．9)和(2．5±0．9)h,AUC_(0～36)分别为(87±28)和(88±30)μg·h·L~(-1),AUC_(0～∞)分别为(94±30)和(97±32)μg·h·L~(-1);按AUC_(0～36)计算,左炔诺孕酮受试制剂的生物利用度为(105±21)%。结论:本方法准确、灵敏、专属,可用于左炔诺孕酮的药动学和生物等效性研究;经统计学检验,受试制剂与参比制剂生物等效。

Determination of levonorgestrel in human plasma by HPLC-MS:application to bioequivalence study

AIM:To establish a fast and sensitive HPLC-MS method for the determiuation of lev- onorgestrel in human plasma and to study the bioequivalence of the test tablets.METHODS:In a random 2- way crossover design,after taking a single oral dose (1.5mg) of levonorgestrel reference tablets and test tablets,plasma samples of 20 healthy male volunteers were prepared by liquid-liquid extraction and then were determined by LC-MS method.RESULTS:The main pharmacokinetic parameters of levonorgestrel of the refer- ence tablets and test tablets were as follow:t_(1/2) were (11.2±s 2.4) and (12±3)h,c_(max) were (9±4) and (10±5)μg·L~(-1),t_(max) were (2.5±0.9) and (2.5±0.9)h,AUC_(0-36) were (87±28) and (88±30)μg·h·L~(-1), AUC_(0-∞) were (94±30) and (97±32)μg·h·L~(-1),respectively.The relative bioavailability of the lev- onorgestrel test tablets calculated by AUC_(0-36) was (105±21)%.CONCLUSION:The method is accurate, sensitive and specific for the quantitative determination of levonorgestrel in pharmacokinetic and bioequivalent study.The test tablets and reference tablets are bioequivalent.