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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。
Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of the concentration of anazariazolol in human plasma and to study the bioequivalence of the two azaleas in human. Methods Tinidazole was used as internal standard. The chromatographic column was Agilent TC-C18 (4.6 mm × 150 mm, 5 μm). The mobile phase was acetonitrile: 0.2% formic acid aqueous solution = 70:30 (V / V) (ESI) positive mode, multiple reaction monitoring mode for quantitative analysis. Twenty-four Chinese male healthy volunteers were randomly divided into two groups with 12 in each group, and received 2 mg of test preparation or reference preparation in different periods respectively. The plasma concentration of anastrozole was determined by LC-MS / MS and pharmacokinetic parameters were calculated by WinNonlin software. Results The linear range of azaconazole was 0.168 3 ~ 100 ng · mL-1 with a lower limit of quantification of 0.168 3 ng · mL-1. The intra- and inter-day precision, recovery, and matrix effects met the biological sample test requirements. The main pharmacokinetic parameters were ρmax of (39.6 ± 6.9) and (39.8 ± 7.6) ng · mL-1, respectively, for test and reference preparations; tmax were (1.9 ± 1.1) and ; t1 / 2 were (34.7 ± 8.1) and (35.1 ± 6.6) h respectively; AUC0-∞ were (1 738.9 ± 425.8) and (1 725.7 ± 468.0) ng · h · mL- The relative bioavailability of the preparation was (102.1 ± 10.2)%. Conclusion The method is simple, efficient and sensitive. The main pharmacokinetic parameters of test and reference preparations are not significantly different. The two kinds of anastrozole tablets have bioequivalence in human body.