# Stability-indicating spectrophotometric manipulations for the determination of Letrozole in the presence of its alkali-induced degradation products; towards whiteness and ChlorTox scale perspectives

## TL;DR

This paper introduces new spectrophotometric methods to accurately measure Letrozole, a breast cancer drug, even when it degrades in alkaline conditions.

## Contribution

The study presents three novel stability-indicating spectrophotometric methods for Letrozole quantification in the presence of its degradation products.

## Key findings

- The D2, RD, and DD1 methods showed linearity and accurate recovery for Letrozole quantification.
- The methods were validated and successfully applied to bulk powder, mixtures, and pharmaceutical formulations.
- Environmental and chemical hazard assessments were conducted using the Whiteness tool and ChlorTox scale.

## Abstract

Letrozole (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, laboratory-prepared 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 study.

The online version contains supplementary material available at 10.1186/s13065-025-01416-2.