Green Chromatographic Assay of Toxic Impurities of Cyproheptadine: In Silico Toxicity Profiling.

This article focuses on the development and validation of a highly sensitive, green thin layer chromatography (TLC)-densitometry method for simultaneous quantification of cyproheptadine (CYP), an antihistaminic and anti-serotonin drug used in severe COVID-19 cases, along with its impurity dibenzosuberone (DBS) and its oxidative degradation product 10,11-dihydroxy-dibenzosuberone (DDS). Using in silico toxicity prediction via preADMET software, the study found that DBS and DDS exhibit higher toxicity than CYP, underscoring the need for sensitive detection of these impurities in pharmaceutical formulations. The proposed TLC-densitometric method demonstrated up to 20-fold greater sensitivity than previously reported chromatographic methods, complied with International Conference on Harmonization (ICH) guidelines, and was evaluated as environmentally acceptable through multiple green chemistry assessment tools. Application of the method to commercial CYP tablets showed accurate and precise results without interference from excipients, supporting its suitability for quality control in pharmaceutical analysis.