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

Autor: J. L. Donato, Leila Felix, Rafael E. Barrientos-Astigarraga, Patrícia Moreno, Ronilson Agnaldo Moreno, Paulo Alexandre Rebelo Galvinas, Carlos Eduardo Sverdloff, Ney Carter do Carmo Borges
Rok vydání: 2012
Předmět:
Zdroj: Biomedical Chromatography. 26:1399-1407
ISSN: 0269-3879
DOI: 10.1002/bmc.2711
Popis: 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 C18, 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 Cmax, AUClast and AUC0–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.
Databáze: OpenAIRE
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