Stability Indicating HPLC Method Development for Fulvestrant using QbD Approach Followed by LC-MS

This research introduces a thorough analytical technique for measuring Fulvestrant, an estrogen receptor antagonist utilized in the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women. Fulvestrant functions by competing with natural estrogen for attachment to estrogen receptors, leading to the downregulation and degradation of these receptors, thereby inhibiting the growth of cancer cells. Although it holds clinical importance, there are only few reported analytical methods for its measurement. This research fills that void by creating and validating a dependable stability-indicating HPLC method for the precise and sensitive quantification of Fulvestrant, including the characterization of its degradants through LC-MS. The method development adhered to ICH Q1A (R2) guidelines, including degradation studies conducted under acidic, basic, oxidative, UV light and thermal stress conditions to guarantee the effective separation of Fulvestrant from its degradation products. The optimized chromatographic conditions utilized a JASCO PU2080 plus HPLC system equipped with a HiQSil C18 Column (250mm × 4.6mm, 5²m), with detection performed at 225nm. The method displayed excellent linearity across the 2–12µg/ml range, achieving a correlation coefficient of 0.9983. High precision was observed in the method (%RSD< 2), along with accuracy reflected by mean recoveries ranging from 99.98% to 100.485%, with LOD and LOQ values recorded at 0.210µg/ml and 0.636 µg/ml, respectively. Fulvestrant was found to be vulnerable to acid and alkaline hydrolysis, oxidation, and thermal stress but remained stable when exposed to photodegradation.