Force degradation studies of relugolix: identification, isolation and structure characterization of stress degradation products by using liquid chromatography-mass spectrometry, auto purification mass mediated preparative-high performance liquid chromatography, high resolution mass spectrometry, nuclear magnetic resonance spectroscopy

To assess the stability of Relugolix under stress conditions, identify and characterize the degradation products, it was subjected to hydrolytic and oxidative stress conditions, according to the International Council for Harmonization guideline Q1A (R2). The drug showed degradation in basic and oxidative conditions, while it was stable in acid conditions. Four degradation products were obtained, two from each basic and oxidative degradation, which was separated on a C18 column by using Auto Purification Mass Spectrometer. The four degradant products have not been reported earlier in any of the literature and are being reported here for the first time. HIGHLIGHTSPresent work captures force degradation of Relugolix under acidic, basic, oxidative, photolytic, and thermal conditions as per International Council for Harmonization guidelines.Two degradation products were observed in basic condition marked as Degradation Product-1, Degradation Product-2 and two degradation products were formed in oxidative condition marked as Degradation Product-3, Degradation Product-4. All the four degradants are novel and are not published in any of the literature.Four degradation products were identified and characterized using various high-end analytical techniques such as Liquid Chromatography and Mass Spectrometer, Reversed Phase–High Performance Liquid Chromatography, High Resolution Mass Spectrometer and Nuclear Magnetic Resonance spectroscopy. Present work captures force degradation of Relugolix under acidic, basic, oxidative, photolytic, and thermal conditions as per International Council for Harmonization guidelines. Two degradation products were observed in basic condition marked as Degradation Product-1, Degradation Product-2 and two degradation products were formed in oxidative condition marked as Degradation Product-3, Degradation Product-4. All the four degradants are novel and are not published in any of the literature. Four degradation products were identified and characterized using various high-end analytical techniques such as Liquid Chromatography and Mass Spectrometer, Reversed Phase–High Performance Liquid Chromatography, High Resolution Mass Spectrometer and Nuclear Magnetic Resonance spectroscopy.

为评估瑞格列克（Relugolix）在胁迫条件下的稳定性，鉴定并表征其降解产物，本研究依照国际人用药品注册技术协调会（International Council for Harmonization, ICH）Q1A(R2)指南，对其施加水解与氧化胁迫处理。该药物在碱性及氧化条件下发生降解，而在酸性条件下保持稳定。共获得四种降解产物，碱性与氧化降解途径各产生两种，通过C18色谱柱结合自动纯化质谱（Auto Purification Mass Spectrometer）完成分离。上述四种降解产物此前未见任何文献报道，为本研究首次公开报道。

研究亮点：本研究依照ICH指南，考察了瑞格列克在酸性、碱性、氧化、光解及热胁迫条件下的强制降解行为。碱性条件下得到两种降解产物，分别标记为降解产物-1、降解产物-2；氧化条件下形成两种降解产物，标记为降解产物-3、降解产物-4。四种降解杂质均为新型化合物，未在任何已发表文献中披露。本研究采用液相色谱（Liquid Chromatography）-质谱（Mass Spectrometer）联用技术、反相高效液相色谱（Reversed Phase–High Performance Liquid Chromatography）、高分辨质谱（High Resolution Mass Spectrometer）及核磁共振波谱（Nuclear Magnetic Resonance spectroscopy）等多种高端分析手段，对四种降解产物进行了鉴定与表征。

研究亮点：本研究依照ICH指南，考察了瑞格列克在酸性、碱性、氧化、光解及热胁迫条件下的强制降解行为。碱性条件下得到两种降解产物，分别标记为降解产物-1、降解产物-2；氧化条件下形成两种降解产物，标记为降解产物-3、降解产物-4。四种降解杂质均为新型化合物，未在任何已发表文献中披露。本研究采用液相色谱（Liquid Chromatography）-质谱（Mass Spectrometer）联用技术、反相高效液相色谱（Reversed Phase–High Performance Liquid Chromatography）、高分辨质谱（High Resolution Mass Spectrometer）及核磁共振波谱（Nuclear Magnetic Resonance spectroscopy）等多种高端分析手段，对四种降解产物进行了鉴定与表征。