Abstract
Vortioxetine (VOR) is a new antidepressant drug used to treat major depressive disorder. In this work, a novel, simple, rapid, accurate, precise, selective, stability-indicating, and fully validated high-performance liquid chromatography method with diode array detection (HPLC-DAD) was developed to determine VOR in bulk and pharmaceutical formulations. A Polar-RP column was used, with a mobile phase consisting of acetonitrile (ACN), methanol (MeOH), acetate buffer pH 3.5, and addition of diethylamine (DEA) in the isocratic elution mode. Assessing the stability of the VOR is fundamental to guarantee the efficacy, safety, and quality of drug products. In this study, the VOR active pharmaceutical ingredient (API) and tablets were subjected to a detailed study of forced degradation, using several degrading agents (acid, alkaline, water, heat, light, and oxidation agents). The developed HPLC-DAD method allows the collection of all the essential data to determine degradation kinetics. It was found that the decomposition of vortioxetine is fragile towards oxidative conditions and photolysis, yielding the first-order and second-order kinetic reaction in the above stress conditions, respectively. The degradation products (DPs) were identified by the high-resolution liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) method. The HPLC-DAD method was successfully applied for the quantification of VOR in tablets. Additionally, in silico toxicity prediction of the DPs was performed.
Highlights
Vortioxetine, VOR (1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine) is a novel antidepressant used for the treatment of major depressive disorder (MDD)
To the best of our knowledge, we described the fully validated method for the determination of vortioxetine in bulk and tablets in the presence of all known degradation products formed under different stress testing for the first time
asymmetry factor (As) demonstrated in our previous works concerning the analysis of psychotropic drugs [28], including vortioxetine [15], in systems containing MeOH as an organic modifier, better peak shapes were obtained compared with systems with ACN, but the higher systems efficiency was obtained in eluent systems with ACN
Summary
Vortioxetine, VOR (1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine) is a novel antidepressant used for the treatment of major depressive disorder (MDD). It is a 5-HT1B receptor partial agonist, 5-HT1A receptor agonist as well as 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, and serotonin (5-HT) transporter (SERT) inhibitor [2]. VOR was approved for the treatment of MDD in 2013 by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [3,4]. The drug is available in the form of tablets (Brintellix or Trintellix) in doses of 5 mg, 10 mg, 15 mg, and 20 mg [5]. VOR is a potential drug candidate for fibromyalgia. Recent research indicates that VOR can attenuate fibromyalgia-like symptoms in mice [6]
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