A Novel Stability‑Indicating Method for Determination of Related Substances of Viloxazine Hydrochloride in a Active Pharmaceutical Ingredient (API) form Using RP‑HPLC

Abstract

Introduction: Viloxazine Hydrochloride is a pharmacologically significant compound known for its dual role as a selective norepinephrine reuptake inhibitor and an anti-asthmatic agent. Despite its clinical importance, there is a conspicuous gap in research concerning the detection of related substances that emerge during the manufacturing process of Viloxazine Hydrochloride. This oversight presents a critical concern, as the presence of impurities could significantly affect the drug's safety profile and therapeutic efficacy. The development of a robust High-Performance Liquid Chromatography (HPLC) method for the determination of related substances in Viloxazine Hydrochloride is, therefore, an urgent need.

Objectives: The primary objective is to establish a straightforward, robust, and precise approach for detecting Viloxazine hydrochloride-associated impurities within an Active Pharmaceutical Ingredient(API)through the utilization of reverse-phase high-performance liquid chromatography (RP-HPLC).

Methods: Chromatographic separation was performed on an Agilent Eclipse XDB C8 column (250 mm × 4.6 mm, 5 µm) using a gradient elution mode. The mobile phase consisted of potassium phosphate and acetonitrile in varying ratios, adjusted to pH 2.35 with phosphoric acid. The flow rate was set at 0.8 mL/min, and detection was carried out with a UV detector at 210 nm.

Results: The method was validated according to ICH guidelines, demonstrating specificity, linearity, precision, accuracy, limit of detection, and limit of quantification. Linear regression analysis of the calibration plot showed a strong linear relationship between response and concentration, with a correlation coefficient (r^2) of 0.9998, indicating excellent correlation. The accuracy of identified impurities ranged from 90% to 110%. The limits of detection (LOD) and quantification (LOQ) for impurities were established at 0.01 μg/g and 0.03 μg/g, respectively.

Conclusion: The proposed method proved effective in accurately quantifying Viloxazine     Hydrochloride related impurities in Active Pharmaceutical Ingredient (API) form.