Development of a New Validated Stability-Indicating High-Performance Thin-Layer Chromatography Method for Determination of Dosulepin HCl in Bulk and Marketed Formulation with Characterization of its Degradants by Liquid chromatography–Mass Spectrometry

Abstract

Aim: Dosulepin hydrochloride is a tricyclic antidepressant. It acts by inhibition of the reuptake of biogenic amine and increasing available neurotransmitter levels at the synaptic cleft. The objective of this work is to develop a new validated stability-indicating high-performance thin-layer chromatography (HPTLC) method for the determination of dosulepin hydrochloric acid (HCl) in bulk and marketed formulation and characterization of the degradation products by liquid chromatography–mass spectrometry (LC–MS). Materials and Methods: The HPTLC method development of dosulepin HCl was performed on aluminum plates precoated with silica gel 60 F254 using dichloromethane: toulene: methanol: glacial acetic acid (GAA) (4:4:2:0.2 v/v) with densitometric detection at 220 nm. The method validation was done using linearity, precision, accuracy, and robustness parameter. Results: Linearity range for dosulepin HCl was found in between 150 and 900 ng/band correlation coefficient was 0.996. The % relative standard deviation for accuracy and precision was found <2%. The developed and validated HPTLC method is simple, accurate, precise, and specific. Conclusion: This study concludes that the dosulepin HCl undergoes degradation to different extent under different stress conditions. From the peak purity profile studies, it was confirmed that the peak of the degradation product was not interfering with the peak of drugs. Major acidic and oxidation degradation products were isolated and characterized by LC–MS and probable degradation pathway for dosulepin HCl was determined.