LAUSR

BACKGROUND Elagolix is a Gonadotropin-Releasing Hormone (GnRH) modulator and used for pain relief during endometriosis. OBJECTIVE The present research was performed to develop and validate a simple, novel, fast, sensitive and cost-effective LC-MS compatible chromatographic method for quantification of all prominent organic impurities of Elagolix sodium in tablet formulation with identification of major degradation products. METHOD The optimum separation of the organic impurities of Elagolix sodium was achieved on ACE C18-PFP (250mm x 4.6mm, 5µm) column by employing pH 5.6 acetate buffer and acetonitrile (95:5, %v/v) as mobile phase A; and acetonitrile and methanol (90:10, %v/v) as mobile phase B. UV detection of the drug and impurities was carried out at 210 nm. Forced degradation study was carried out by employing acid, alkali, oxidative, thermal and photolytic stress conditions on Elagolix sodium drug substance and its drug product. The major degradation products observed during stress study were identified by using mass spectrometry. RESULTS Elagolix sodium and its prominent organic impurities were resolved in the developed method through the gradient elution program of 46 minutes at a flow rate of 1.3 mL/min. Significant degradation was observed during alkali hydrolysis and oxidative stress conditions with a mass balance of more than 97.0%. The method was validated in-line with present ICH Q2(R1) guidelines. CONCLUSIONS Forced degradation study suggests that the developed method is specific and stability- indicating and can be used for related substance analysis of Elagolix drug substance and its dosage forms. HIGHLIGHTS This is the first research paper which describes a simple and sensitive (Detection limit: 0.08 µg/mL) HPLC method for quantification of all probable impurities of Elagolix in tablet dosage forms. The noticeable feature of the developed method is resolution of impurities of similar structures in a quick time by using routine solvents which are easily available in QC laboratory.