Determination of Mirtazapine in Human Plasma by HPLC-MS and Bioavailability of Newly Developed Mirtazapine Tablets in Healthy Volunteers

摘要

Aim To estabhsh a sensitive and specific liquid chromatography-mass spectrometry method for determination of mirtazapine in human plasma and evaluation of its relative bioavailabihty. Methods After being alkalized by 25% ammonia, mirtazapine in the plasma was extracted with n-hexane. Desloratadine was used as internal standard (IS). Solutes were separated on a C18 column with a mobile phase of methanol-ammonium acetate buffer (pH3.5) (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 paramneters 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 estabhshed HPLC-MS method is rapid, sensitive and specific for the detemtination of mirtazapine in human plasma. The relative bioavailability was 100.0%±10.8%.