Comprehensive Analytical Investigation of the Photodegradation of Olopatadine and In Silico Toxicity Assessment of...

Olopatadine (OLO) is a second-generation antihistamine approved for the treatment of allergic conjunctivitis as ophthalmic and nasal solutions. Due to its intrinsic absorption in the near-UV region (approximately 300 nm), OLO may be susceptible to photodegradation and understanding this behavior is essential for ensuring the quality and safety of OLO-containing pharmaceutical formulations. The forced photodegradation of OLO was investigated under UV/Vis irradiation (300-800 nm) over a wide pH range. Photodegradation kinetics was evaluated using a selective LC-UV method. OLO degradation followed first-order kinetics, with rate constants ranging from 3.45 × 10^-5 to 6.91 × 10^-5 s^-1, corresponding to degradation levels in the range 45.54-81.95%. Photodegradation products were characterized using UHPLC-HRMS/MS, leading to the identification of twelve, including seven previously unreported compounds. Seven degradants were isolated by preparative LC-UV and their structures were confirmed by NMR spectroscopy, including three newly reported compounds. The potential toxicity of all identified photodegradants was evaluated using the in silico tools OSIRIS Property Explorer and Toxtree. Five products were predicted to exhibit reproductive toxicity and irritation potential, whereas one compound showed a potential tumorigenic risk. Overall, this study provides comprehensive insight into the photostability of OLO and the formation of its photodegradation products.