El-Fatah Nourhan A Abd, Fouad Manal Mohammed, Hegazy Maha A, El-Sayed Ghada M
Analytical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th October City, Giza, 11787, Egypt.
Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, 11651, Egypt.
BMC Chem. 2025 Mar 8;19(1):63. doi: 10.1186/s13065-025-01416-2.
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 (D) 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 (DD) through recording peak amplitude at 246.0 nm. Linearity ranged from 1.00 to 16.00 µg/mL for D, while from 3.00 to 16.00 µg/mL for RD and DD with adequate recoveries 100.02 ± 1.371, 100.05 ± 1.972 and 100.40 ± 1.223 for D, RD and DD, 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.
来曲唑（LTZ）是一种既定的乳腺癌一线激素治疗药物，但由于存在氰基苯基，发现它在碱性介质中极易降解。因此，首次开发了三种稳定性指示分光光度法，用于在其碱诱导降解产物存在的情况下对LTZ进行定量；确保方法的简便性、灵敏度和准确性。第一种方法是二阶导数（D），通过记录药物在226.8 nm处的峰高。第二种方法是比率差值（RD），在波长240.0 nm和258.0 nm处记录峰高。第三种方法是比率光谱的一阶导数（DD），通过记录246.0 nm处的峰高。D法的线性范围为1.00至16.00 μg/mL，而RD法和DD法的线性范围为3.00至16.00 μg/mL，D法、RD法和DD法的回收率分别为100.02±1.371、100.05±1.972和100.40±1.223。所提出的方法按照ICH指南进行了验证，并成功应用于原料药粉末、实验室制备的混合物和药物制剂中LTZ的测定。还使用了采用RBG12算法的白度工具来评估环境方面，同时使用ChlorTox量表来评估本研究中化学品的危害。
