Green and white-assessed validated chromatographic methods for Ondansetron purity testing in its pharmaceutical formulations; in silico toxicity profiling of impurities

Abstract

Drug impurities are seen as a crucial threat to drug safety, specifically when dealing with mutagenic/ toxic impurities. Here, we present LC-MS/MS and HPTLC-densitometric methods for simultaneous quantification of Ondansetron and its four official impurities. For the LC-MS/MS, the isocratic elution was applied using methanol and water containing 0.1 % formic acid in a ratio (70:30 v/v) at a flow rate of 1 mL/min, a stationary phase C18 column (4.6 × 50 mm, 5 µm) and mass detection using the MRM mode. For the HPTLC-densitometric method, the mobile phase consists of ethyl acetate: methanol in a ratio (6:4 v/v), and the UV detection was at 216 nm. The developed methods have been validated per ICH recommendations and then evaluated using five tools for whiteness and greenness assessment, offering promising results in comparison to reported chromatographic methods. Additionally, the toxicity profile of the impurities was expected by the online software; PreADMET and pkCSM. The developed methods are recommended for quality control due to their high analytical performance as well as their sustainability, simplicity, and cost-effectiveness, which improves the surveillance capability.