目的建立高效液相色谱-串联质谱的方法测定人血浆内的依西美坦浓度,对两种制剂进行人体生物等效性研究。方法采用Lichrospher C₁₈(4.6mm×150mm,5μm)色谱柱;柱温25℃;流动相为甲醇-水(含0.05%甲酸)(80∶20);流速为1.0mL·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;检测离子为依西美坦m/z 296.8[M+H]⁺→121[M+H]⁺,非那雄胺(内标)m/z373.2[M+H]⁺→305.2[M+H]⁺。结果依西美坦的线性范围为0.0994～39.76μg·L^-1,依西美坦受试制剂和参比制剂的t_1/2分别为(13.37±4.62)和(15.65±5.89)h,ρ^max分别为(19.97±8.51)和(20.04±9.16)μg·L^-1,t_max分别为(0.95±0.39)和(0.90±0.29)h,AUC_0-72分别为(95.64±26.87)和(96.73±25.97)μg·h·L^-1,AUC_0-∞分别为(100.47±28.76)和(114.59±62.32)μg·h·L^-1。结论该方法简便、灵敏度高,两制剂生物等效。

OBJECTIVE To develop a high-performance liquid chromatographic mass spectrometric method for the determination of exemestane in human plasma and to study the bioequivalence of two preparations in human.METHODS A lichrospher C₁₈(4.6 mm×150 mm, 5 μm) chromatographic column was used of 25 ℃. The mobile phase consisted of methanol-water(contained 0.05% methanoic acid) (80∶20) at the flow-rate of 1.0 mL·min^-1. A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source (APCI) was used as detector and operated in the positive ion mode and selected reaction monitoring (SRM). The ion of exemestane to detect was m/z 296.8 [M+H]⁺→121 [M+H]⁺, and the finasteride ion ( internal standard) was m/z 373.2 [M+H]⁺→305.2 [M+H]⁺. RESULTS The standard curve was linear in a range of 0.099 4～39.76 μg·L^-1. The main pharmacokinetic parameters of t_1/2,ρ_max,t_max,AUC_0-72 and AUC _0-∞ were (13.37±4.62)h, (19.97±8.51) μg·L^-1, (0.95±0.39)h, (95.64±26.87) μg·h·L^-1, (100.47±28.76) μg·h·L^-1 for the test preparation; (15.65±5.89) h, (20.04±9.16) μg·L^-1, (0.90±0.29) h, (96.73±25.97) μg·h·L^-1, (114.59±62.32) μg·h·L^-1 for the reference preparation.CONCLUSION This method is simple, sensitive and suitable for clinical pharmacokinetics or bioequivalence studies.The two preparations are bioequivalent.