【摘要】 目的建立液相色谱-串联质谱(LC-MS/MS)法测定人血浆中阿那罗唑浓度,用于研究两种阿那罗唑片在人体内的生物等效性。方法以替硝唑为内标,色谱柱为Agilent TC-C18(4.6 mm×150 mm,5μm),流动相为乙腈∶0.2%甲酸水溶液=70∶30(V/V),采用电喷雾离子源(ESI)正离子模式,多反应监测模式进行定量分析。24例中国男性健康志愿者随机分为两组,每组12人,于不同周期分别单次口服受试制剂或参比制剂2 mg。采用LC-MS/MS法测定阿那罗唑血药浓度并用WinNonlin软件计算药动学参数。结果阿那罗唑线性范围为0.168 3～100 ng·mL-1,定量下限为0.168 3 ng·mL-1,日内及日间精密度、回收率、基质效应均符合生物样品测试要求。主要药动学参数为:受试制剂和参比制剂的ρmax分别为(39.6±6.9)、(39.8±7.6)ng·mL-1;tmax分别为(1.9±1.1)、(2.2±1.3)h;t1/2分别为(34.7±8.1)、(35.1±6.6)h;AUC0-∞分别为(1 738.9±425.8)、(1 725.7±468.0)ng·h·mL-1;受试制剂对参比制剂的相对生物利用度为(102.1±10.2)%。结论该方法简单、高效、灵敏,测得受试制剂与参比制剂主要药动学参数无显著差异,两种阿那罗唑片在人体内具有生物等效性。更多还原

【Abstract】 AIM To establish a LC-MS/MS method for the study of the determination and bioequivalence of anastrozole in human plasma. METHODS Tinidazole was used as the internal standard, with Agilent TC-C18(4.6 × 150 mm, 5 μm) as analytical column and mobile phase consisting of acetonitrile ∶ 0.2% formic acid(70 ∶ 30, V/V). The ionization was optimized with ESI(+) and selectivity was enhanced with tandem mass spectrometric analysis via multiple reaction monitoring( MRM) functions. A single oral dose of 2 mg test or reference preparation(12 volunteers for each preparation) were given to 24 health volunteers according to an randomized crossover study. The plasma concentration was determined by LC-MS/MS method and the pharmacokinetics parameters were calculated by WinNonlin. RESULTS Good linearity was found within 0.168 3-100 ng·mL-1and the limit of quantitative( LOQ) concentration was 0.168 3 ng·mL-1. Results of methodology specificity, accuracy, recovery and matrix effect fit the requirements of sample determination. The main pharmacokinetic parameters test and reference preparations were as follows: ρmaxwere(39.6 ± 6.9) and(39.8 ±7.6) ng·mL-1, tmaxwere(1.9 ± 1.1) and(2.2 ± 1.3) h, t1/2were(34.7 ± 8.1) and(35.1 ± 6.6) h, AUC0-∞were(1 738.9 ± 425.8) and(1 725.7 ± 468.0) ng·h·mL-1, respectively. The relative bioavailability of test to reference preparation was( 102.1 ± 10.2) %. CONCLUSION The method is simple, sensitive and reliable.The results of statistics analysis showed that the reference preparation and the test preparation were bioequivalent.更多还原