Light-Induced Degradation of Tamoxifen in Liquid Formulations: Multivariate Kinetic Profiling, Stabilization Strategies, and Estrogen Receptor Binding

Tamoxifen is the most prescribed drug for the treatment of breast cancer in premenopausal women and prevention of tumor recurrence. The anticancer effect is attributed to its ability to modulate estrogen receptor activity, with the drug's metabolites being more effective than the parent compound. Tamoxifen is sensitive to environmental conditions, leading to the formation of degradation products that may, however, retain biological activity. Herein, the photodegradation of tamoxifen in oral formulations was studied by combining spectrophotometric methodologies and multivariate analysis. The four photoproducts identified have been studied. Stabilization strategies were explored, evaluating both protective packaging precautions and the addition of chemical stabilizers, such as ascorbic acid and quercetin. Molecular docking simulations revealed that all four photoderivatives are capable of binding to the estrogen receptor, suggesting that these compounds may retain, or contribute to, the drug's antitumor activity. These findings not only underscore the importance of formulation and storage conditions in preserving tamoxifen stability and therapeutic efficacy but also provide the first integrated multivariate kinetic and molecular docking analysis of its photodegradation in liquid formulations, offering novel insights into both stability and residual pharmacological activity.