title: A fast, sensitive and simple method for mirtazapine quantification in human plasma by HPLC-ESI-MS/MS. Application to a comparative bioavailability study.
abstract: 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.
authors.affiliation: Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos S/S Ltda, 24 Cesar Bierrenbach St, Campinas, SP, Brazil.
authors.forename: Ney Carter
authors.initials: NC
authors.lastname: Borges
authors.forename: Rafael Eliseo
authors.initials: RE
authors.lastname: Barrientos-Astigarraga
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Sverdloff
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Donato
authors.forename: Patricia
authors.initials: P
authors.lastname: Moreno
authors.forename: Leila
authors.initials: L
authors.lastname: Felix
authors.forename: Paulo Alexandre Rebelo
authors.initials: PA
authors.lastname: Galvinas
authors.forename: Ronilson Agnaldo
authors.initials: RA
authors.lastname: Moreno
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D003987:Dibenzothiazepines / Q000097:blood; D004355:Drug Stability; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008875:Middle Aged; D000078785:Mirtazapine; D000069348:Quetiapine Fumarate; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003987:Dibenzothiazepines; D008803:Mianserin; D000069348:Quetiapine Fumarate; D000078785:Mirtazapine