Development of Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Mazindol in Human Plasma: Application to a Bioequivalence Study of Daewon Sanorex Tablet® (Mazindol 1 mg)

Introduction: A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method to determine mazindol in human plasma is needed for bioequivalence and pharmacokinetic studies of celecoxib preparations. The present study describes a simple, rapid, reproducible, and reliable LC-MS/MS method to determine mazindol concentrations in human plasma. Method: After one-step liquid-liquid extraction (LLE) using ethyl acetate : hexane = 8 : 2, mazindol and fluoxetine (internal standard, IS) were eluted on a Kinetex HILLIC column (50.0 × 2.1mm i.d. 2.6 µm) with an isocratic mobile phase, which consisted of 20 mM ammonium formate in water: acetonitrile (20:80, v/v) at a flow rate of 0.2 mL/min. The calibration curve was linear (correlation coefficient were > 0.99) over the concentration range (0.05-10 ng/mL). Results: The intraday and interday precisions ranged 0.74 - 8.78% and 4.49 - 7.49%, respectively, and its accuracies ranged 92.00 - 108.48% and 97.73 - 105.20%, respectively. The stability of mazindol was evaluated by the addition of buffer to the plasma. Conclusion: The devised method was successfully applied to bioequivalence study of two formulations of mazindol, Sanorex tablet® and Mazanor tablet® in 50 healthy Korean male volunteers following single oral administration.