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

This paper details the development and validation of a novel, stability-indicating High-Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD) method for the quantitative analysis of vortioxetine (VOR), an antidepressant drug, in both bulk form and pharmaceutical formulations. The primary objective was to assess VOR's stability under various stress conditions, including acid, alkaline, water, heat, light, and oxidation, and to identify its degradation products (DPs). The method utilized a Polar-RP column with an isocratic mobile phase comprising acetonitrile, methanol, acetate buffer (pH 3.5), and diethylamine. Forced degradation studies revealed that VOR is particularly susceptible to oxidative conditions and photolysis, exhibiting first-order and second-order degradation kinetics, respectively. Seven degradation products were identified and characterized using high-resolution liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). The developed HPLC-DAD method demonstrated excellent linearity (1–100 µg/mL, r = 0.9999), sensitivity (LLOD of 1.32 µg/mL, LLOQ of 3.99 µg/mL), accuracy, precision, and selectivity, making it suitable for routine quality control and stability studies. Furthermore, in silico toxicity predictions were performed on the identified DPs, indicating potential mutagenic or carcinogenic effects for some, highlighting the importance of comprehensive stability assessments.

This paper details the development and validation of a novel, stability-indicating High-Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD) method for the quantitative analysis of vortioxetine (VOR), an antidepressant drug, in both bulk form and pharmaceutical formulations. The primary objective was to assess VOR's stability under various stress conditions, including acid, alkaline, water, heat, light, and oxidation, and to identify its degradation products (DPs). The method utilized a Polar-RP column with an isocratic mobile phase comprising acetonitrile, methanol, acetate buffer (pH 3.5), and diethylamine. Forced degradation studies revealed that VOR is particularly susceptible to oxidative conditions and photolysis, exhibiting first-order and second-order degradation kinetics, respectively. Seven degradation products were identified and characterized using high-resolution liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). The developed HPLC-DAD method demonstrated excellent linearity (1–100 µg/mL, r = 0.9999), sensitivity (LLOD of 1.32 µg/mL, LLOQ of 3.99 µg/mL), accuracy, precision, and selectivity, making it suitable for routine quality control and stability studies. Furthermore, in silico toxicity predictions were performed on the identified DPs, indicating potential mutagenic or carcinogenic effects for some, highlighting the importance of comprehensive stability assessments. Research Background and Significance Vortioxetine (VOR) is a multimodal antidepressant widely used for the treatment of major depressive disorder. Given the critical importance of drug stability in pharmaceutical development and quality control, understanding the degradation behavior of VOR under variou