关键词: 米氮平, 米氮平, 米氮平, 药物动力学, 药物动力学, 药物动力学, 生物利用度, 生物利用度, 生物利用度, 液质联用, 液质联用, 液质联用

Abstract: Aim To establish a sensitive and specific liquid chromatography-mass spectrometry method for determination of mirtazapine in human plasma and evaluation of its relative bioavailability. Methods After being alkalized by 25% ammonia, mirtazapine in the plasma was extracted with n-hexane. Desloratadine was used as internal standard (IS). Solu-tes were separated on a C18 column with a mobile phase of methanol-ammonium acetate buffer (pH 3.5) (75:25). The flow rate of the mobile phase was 1 mL·min^-1. Detection was performed on an electrospray ionization (ESI) mass spectrometer and operated in selected ion monitoring (SIM) and positive-ionization mode using target ionsat m/z 266.2 for mirtazapine and m/z 311.2 for the IS. The fragmentor voltage was 90 V. A randomized cross-over study was performed in 20 healthy volunteers. In the two study periods, twenty healthy Chinese male subjects received a single oral dose of mirtazapine 30 mg. Results The calibration curve was linear over the range of 0.3-200 ng·mL^-1. The limit of quantitation was 0.1 ng·mL^-1. The parameters for mirtazapine test tablet and reference tablet were as follows: T1/2(24.7±4.1) and (23.6±4.3) h, Tmax(1.6±0.8) and (1.5±0.8) h, Cmax(95.9±29.8) and (91.9±26.7) ng·mL^-1, respectively. Conclusion The established HPLC-MS method is rapid, sensitive and specific for the determination of mirtazapine in human plasma. The relative bioavailability was 100.0%±10.8%.

Key words: mirtazapine, mirtazapine, pharmacokinetics, pharmacokinetics, bioavailability, bioavailability, HPLC-MS, HPLC-MS