Development of the Validated Stability-Indicating Method for the Determination of Vortioxetine in Bulk and Pharmaceutical Formulation by HPLC-DAD, Stress Degradation Kinetics Studies and Detection of Degradation Products by LC-ESI-QTOF-MS

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.

MassChemSite for In-Depth Forced Degradation Analysis of PARP Inhibitors Olaparib, Rucaparib, and Niraparib

“…Indeed, the investigation of a drug’s degradation behavior toward various stressed conditions as well as the characterization of the DP structures is an integral part of the pharmaceutical drug development process. , Moreover, it is also pivotal for the design of the manufacturing process, shelf-life determination, formulation, and packaging development. In detail, forced degradation studies aim to accelerate the formation of DPs by exposing the drug to different physicochemical stress conditions to evaluate its stability and degradation pathways. , High-performance liquid chromatography (HPLC) or ultra HPLC (UHPLC) coupled with high-resolution mass spectrometry (HRMS) and/or with UV–vis detectors represent the analytical technique commonly used to evaluate DPs allowing both their structure elucidation and quantification. ,− Several regulatory agencies (e.g., FDA, WHO, and ICH) recommend exposure of the drug to acidic, basic, dry heat, oxidation, and light (UV) stress conditions among others. , The same agencies indicate in their protocols the ranges of pH, temperature, and maximum exposure time recommended to perform these studies. However, the conditions reported are not stringent.…”