A fast, sensitive and simple method for mirtazapine quantification in human plasma by HPLC‐ESI‐MS/MS. Application to a comparative bioavailability study

In the present study a simple, fast, sensitive and robust method to quantify mirtazapine in human plasma using quetiapine as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by a simple protein precipitation with methanol and were analyzed by high‐performance liquid chromatography coupled to an electrospray tandem triple quadrupole mass spectrometer (HPLC‐ESI‐MS/MS). Chromatography was performed isocratically on a C 18 , 5 µm analytical column and the run time was 1.8 min. The lower limit of quantitation was 0.5 ng/mL and a linear calibration curve over the range 0.5–150 ng/mL was obtained, showing acceptable accuracy and precision. This analytical method was applied in a relative bioavailability study in order to compare a test mirtazapine 30 mg single‐dose formulation vs a reference formulation in 31 volunteers of both sexes. The study was conducted in an open randomized two‐period crossover design and with a 14 day washout period. Since the 90% confidence interval for C max , AUC last and AUC 0–inf were within the 80–125% interval proposed by the Food and Drug Administration and ANVISA (Brazilian Health Surveillance Agency), it was concluded that mirtazapine 30 mg/dose is bioequivalent to the reference formulation, according to both the rate and extent of absorption. Copyright © 2012 John Wiley & Sons, Ltd.