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目的:建立人血浆中烯丙雌醇的LC-MS/MS浓度测定方法,并评价国产与进口烯丙雌醇片的人体生物等效性。方法:采用Curosil-PFP色谱柱(250 mm×4.6 mm,5μm);柱温25℃;流动相为甲醇-水(95∶5);流速为1.0 mL.min-1;通过液相串联质谱,大气压化学电离(APCI),以选择反应监测(SRM)方式进行检测。结果:血浆中烯丙雌醇的最低定量限为0.04 ng.mL-1,在0.04~20.0 ng.mL-1范围内线性关系良好,批内及批间精密度RSD分别小于1.3%和3.1%。受试制剂与参比制剂的各主要药动学参数:Tmax分别为(1.9±0.5)和(2.0±0.7)h,Cmax分别为(13.63±4.05)和(13.00±3.77)ng.mL-1,t1/2分别为(9.46±2.88)和(8.77±3.53)h,用梯形法计算AUC0~36 h分别为(46.88±17.48)和(45.16±16.81)ng.h.mL-1。2种制剂的主要药动学参数Cmax和AUC0~36 h经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明2种制剂生物等效,相对生物利用度为(106.4±29.1)%。结论:该方法简便、灵敏度高,2种烯丙雌醇制剂在人体内生物等效。
OBJECTIVE: To establish a method for the determination of allyl estradiol in human plasma by HPLC and to evaluate the bioequivalence of allyl estradiol tablets in China. Methods: The Curosil-PFP column (250 mm × 4.6 mm, 5 μm) was used. The column temperature was 25 ℃. The mobile phase consisted of methanol and water (95: 5) Atmospheric pressure chemical ionization (APCI) was performed using a selective reaction monitoring (SRM) approach. Results: The lowest limit of quantification of allyl estradiol in plasma was 0.04 ng.mL-1, with good linearity in the range of 0.04-20.0 ng.mL-1. The intra-and inter-batch precision RSD was less than 1.3% and 3.1% . The main pharmacokinetic parameters of test and reference preparations were Tmax (1.9 ± 0.5) and (2.0 ± 0.7) h, respectively, with Cmax of (13.63 ± 4.05) and (13.00 ± 3.77) ng.mL-1 , and t1 / 2 were (9.46 ± 2.88) and (8.77 ± 3.53) h, respectively. Trapezoidal method was used to calculate AUC from 0 to 36 h (46.88 ± 17.48) and (45.16 ± 16.81) ng.h.mL- The pharmacokinetic parameters Cmax and AUC0 ~ 36 h were logarithmically transformed and analyzed by ANOVA and double unilateral t-test. The 90% confidence interval was calculated, indicating that the two formulations were bioequivalent and the relative bioavailability was (106.4 ± 29.1)%. Conclusion: The method is simple and sensitive, and two allyl estradiol preparations are bioequivalent in human.