QUANTITATIVE ANALYSIS OF ELACESTRANT IN PHARMACEUTICAL DOSAGE FORMS BY ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY WITH EMPHASIS ON STABILITY ASSESSMENT

Abstract

Objectives: Elacestrant, an estrogen receptor antagonist, inhibits the proliferation of estrogen-dependent cancer cells. A novel, sensitive, and user-friendly liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the identification and quantification of elacestrant in pharmaceutical formulations.

Methods: The analytical method employed an Agilent Eclipse XDB-C18 column with dimensions of 150 × 4.6 mm and a particle size of 3.5 μm. The chromatographic separation was achieved using isocratic elution at a flow rate of 1.0 mL/min. For detection, a photodiode array (PDA) detector was utilized in conjunction with tandem mass spectrometry (MS/MS), enabling both qualitative and quantitative analysis with high sensitivity and specificity.

Results: The method demonstrated excellent linearity over a concentration range of 25–150 μg/mL (R2=0.99979). The limit of detection and limit of quantitation were found to be 0.3 μg/mL and 1.0 μg/mL, respectively. Intra- (0.189) and inter-day (0.405) precision studies showed relative standard deviations (% RSDs) of <1%. Recovery rates ranged from 99.20% to 101.30%, and the percentage RSD values ranged from 0.36 to 0.645. The robustness of the new approach is demonstrated by the observed change in peak area, which was within limits, or <8.0%. Elacestrant has lower susceptibility toward thermal, photolytic (light/ultraviolet), and reduction degradation conditions, whereas its sensitivity toward peroxide, acid, alkali, and hydrolysis degradation conditions is evident from the high degradation levels. Mass spectrum give Molecular ion: m/z: 459.6463, base peak m/z: 174.630 and give another fragment ions m/z: 388.5172, m/z: 303.41652, m/z: 232.316.

Conclusion: The developed LC-MS/MS method is accurate, precise, robust, and linear for the determination of elacestrant in tablet formulations. With recovery rates within acceptable limits and degradation behavior consistent under stress conditions, the method is suitable for routine quality control and stability testing of pharmaceutical products containing elacestrant.