Abstract
Vilazodone is a novel antidepressant agent, approved by the US Food and Drug Administration (US FDA) for the treatment of major depressive disorder. In this study, a fast sensitive ultra-high performance liquid chromatography-tandem mass spectroscopy method was developed and validated for the determination of vilazodone in human plasma. After a simple protein precipitation by acetonitrile, both vilazodone and risperidone (internal standard, IS) were separated on an Acquity UPLC BEH™ C18 column (50 × 2.1 mm, 1.7 µm). An isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v) was used at the 0.3 mL/min flow rate. Both vilazodone and IS were eluted at 0.44 and 0.47 min, respectively, having a run time of 1.0 min. Detection and quantification were performed using an electrospray ionization source in positive mode by multiple reaction monitoring. The precursor to product ion transitions were monitored at m/z 442.19 > 154.99 for vilazodone and m/z 411.18 > 191.07 for IS, respectively. The standard curve (0.40-500 ng/mL) was found to be linear with a lower limit of quantification 0.40 ng/mL. All validation results were found to be within acceptable limits as per guidelines for bioanalytical method validation (US FDA and European Medicines Agency). To the best of our knowledge, this is the first fully validated assay for the determination of vilazodone in human plasma and was successfully applied to an oral pharmacokinetic study in rats.