| Objective: To develop two sensitive and specific LC/MS/MS methods for respective determination of valsartan and mirtazapine in human plasma and to study the bioequivalences of different formulations containing valsartan and mirtazapine and clinical investigations of their pharmacokinetics, respectively. Method: For determination of the plasma concentration of valsartan, an aliquot of 50-μL plasma was treated by liquid-liquid extraction, then the analytes of interest were analyzed on a Zorbax SB-C18 column with the mobile phase consisted of methanol-5 mmol/L ammonium acetate (80: 20, v/v). For determination of the plasma concentration of mirtazapine, an aliquot of 50-μL plasma was treated by precipitation. The analytes of interest were separated on a Zorbax SB-C8 column with the mobile phase consisting of acetonitrile-water-formic acid (80: 20: 0.2, v/v/v). A Thermo Finnigan TSQ Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor → product ion combination of m/z 436 → m/z 207,235,291 and m/z 441→m/z 263 was used to respectively quantify valsartan and candesartan, m/z 266 → m/z 195 and m/z 256→ m/z 167 was used to respectively quantify mirtazapine and diphenhydramine. Results: The linear calibration curves were obtained in the concentration range of 4.0-8000 ng/mL and 0.18-144.0 ng/mL for valsartan and mirtazapine, respectively. The intra- and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 15%. Accuracy determined at three QC concentrations was within ± 15% as terms of relative error (RE). Each plasma sample was chromatographed within 3.6 min. Conclusion: The methods were sensitive and convenient, and proved to be suitable for bioequivalence evaluations of different formulations containing valsartan and mirtazapine, respectively.
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