AIM:To develop a rapid,sensitive and specific LC/MS/MS method for direct determination of mirtazapine in human plasma and
to study the bioequivalence of different formulations containing mirtazapine. METHODS:The plasma concentration of mirtazapine was determined with an aliquot of 50μL plasma treated by precipitation. The analytes of interest were separated on a Zorbax SB-C_8 column with the mobile phase consisting of acetonitrile-water-formic acid (80:20:0.2). A Finnigan TSQ Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Each plasma sample was chromatographed within 3.5 min. RESULTS:The linear calibration curves were obtained in the concentration range of 0.18-144.0μg·L~(-1). The lower limit of quantification was 0.18 μg·L~(-1). The intra- and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 6.2 %. Accuracy determined at three concentrations(0.36, 7.20 and 115.2 μg·L~(-1) for mirtazapine) ranged from 100.6 ％ to 102.0 %.
Pharmacokinetic parameters of mirtazapine reference formulation was obtained as follows:t_(max) mwas( 1.4 ±s 0.7) h, c_(max) was (65± 35)μg·L~(-1), t_(l/2) was (24± 6) h, AUC_(0-96) was (814± 419) μg·h·L~(-1), pharmacokinetic parameters of mirtazapine test formulation were obtained as follows: t_(max) was (1.4 ± 0.7) h,c_(max) was(69±35) μg·L~(-1), /,2was (24 ±6) h,AUC_(0-96) was (842±387) μg·h·L~(-1). Calculated with AUC_(0-96), the bioavailability of two formulations was(102 ±18) %. CONCLUSION :LC/MS/MS method is sensitive, convenient and proved to be suitable for bioequivalence evaluation of different formulations containing mirtazapine and also for clinical investigation of mirtazapine
pharmacokinetics.