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

Biomed Chromatogr 2012 Nov 16;26(11):1399-407. Epub 2012 Feb 16.

Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos S/S Ltda, 24 Cesar Bierrenbach St, Campinas, SP, Brazil.

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.

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http://dx.doi.org/10.1002/bmc.2711DOI Listing
November 2012
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