Nourhan A. Abd El-FatahManal Mohammed FouadMaha A. HegazyGhada M. El-Sayed2025-04-022025-04-022025-03-08El-Fatah, N. a. A., Fouad, M. M., Hegazy, M. A., & El-Sayed, G. M. (2025). Stability-indicating spectrophotometric manipulations for the determination of Letrozole in the presence of its alkali-induced degradation products; towards whiteness and ChlorTox scale perspectives. BMC Chemistry, 19(1). https://doi.org/10.1186/s13065-025-01416-2https://doi.org/10.1186/s13065-025-01416-2https://repository.msa.edu.eg/handle/123456789/6364Q2Letrozole (LTZ) is an established first hormonal treatment for breast cancer, yet it was found to be highly susceptible for degradation in alkaline medium due to the presence of cyano phenyl group. Consequently, three stability-indicating spectrophotometric manipulations for LTZ quantification in presence of its alkali-induced degradation products were developed for the first time; ensuring methods’ simplicity, sensitivity and accuracy. The first method was Second derivative (D2) by recording peak amplitude of the drug at 226.8 nm. The second method was Ratio difference (RD) where the peak amplitude were recorded at wavelengths 240.0 nm and 258.0 nm. The third method was First derivative of ratio spectra (DD1) through recording peak amplitude at 246.0 nm. Linearity ranged from 1.00 to 16.00 µg/mL for D2, while from 3.00 to 16.00 µg/mL for RD and DD1 with adequate recoveries 100.02±1.371, 100.05±1.972 and 100.40±1.223 for D2, RD and DD1, respectively. The proposed methods were validated as per ICH guidelines, and were successfully applied for determination of LTZ in bulk powder, laboratoryprepared mixtures, and pharmaceutical formulation. The Whiteness tool, using the RBG12 algorithm, was employed to evaluate environmental aspects, as well, ChlorTox scale was used to assess chemicals’ hazards for this studyen-USLetrozoleAlkali-induced degradation productsSpectrophotometryWhiteness evaluationClorTox assessmentArticlehttps://doi.org/10.1186/s13065-025-01416-2