Three new and five known steroidal compounds as impurities in nomegestrol acetate（I） were isolated from the enriched mother liquor via various chromatographic methods. Their structures were elucidated by spectrometr...Three new and five known steroidal compounds as impurities in nomegestrol acetate（I） were isolated from the enriched mother liquor via various chromatographic methods. Their structures were elucidated by spectrometric analysis and single-crystal X-ray diffraction analysis. New compounds were characterized as 17a-hydroxyl-3-oxoes- trane-5β, 17-dicarbonitrile（l）, 4-ethyl- 17a-hydroxyl-3-oxoestr-4-en- 17-carbonitrile（2）, 4-ethylestr-4-en-3,17-dione（3）. The ^13C NMR data of known estrane derivatives（4--7） were also reported first time in this paper. The study may be helpful to identifing and characterizing all the impurities that are present at a level of 0.1% and be useful in the quality control of the production ofnomegestrol acetate.展开更多
Polymorph screening is currently one of the most important strategies of innovators and generic companies from both pharmaceutical and intellectual property rights perspectives.Different polymorphs may have varying ph...Polymorph screening is currently one of the most important strategies of innovators and generic companies from both pharmaceutical and intellectual property rights perspectives.Different polymorphs may have varying physicochemical properties which influence the bioavailability.The purpose of this study was to investigate the crystal structures and physicochemical properties of Nomegestrol acetate(NOMAC)polymorphs.Forms Ⅰ and Ⅱ(dioxane solvate)were isolated and prepared by systemic crystallization screening in this study,and the forms are reported for the first time.A structural analysis and comparison of all the forms are presented.This study was also the first time to apply a rapid and feasible ultra-highperformance-liquid chromatography(UHPLC)-electrospray ionization(ESI)-tandem mass spectrometry(MS)method to determine plasma levels of NOMAC within 3.0 mins.And this study demonstrated that the optimal crystal Form Ⅰ displayed higher bioavailability than API indicating that Form I could be an alternative solid form that needs further research.展开更多
基金Supported by the National Natural Science Foundation of China(No.20802031)the Scientific Research Funds of Lanzhou University of Technology,China(No.SB08200605)
文摘Three new and five known steroidal compounds as impurities in nomegestrol acetate（I） were isolated from the enriched mother liquor via various chromatographic methods. Their structures were elucidated by spectrometric analysis and single-crystal X-ray diffraction analysis. New compounds were characterized as 17a-hydroxyl-3-oxoes- trane-5β, 17-dicarbonitrile（l）, 4-ethyl- 17a-hydroxyl-3-oxoestr-4-en- 17-carbonitrile（2）, 4-ethylestr-4-en-3,17-dione（3）. The ^13C NMR data of known estrane derivatives（4--7） were also reported first time in this paper. The study may be helpful to identifing and characterizing all the impurities that are present at a level of 0.1% and be useful in the quality control of the production ofnomegestrol acetate.
基金supported by the National Key R&D Program of China(No.2016YFC1000901)the innovation fund of National Research Institute for Family Planning(No.KYS[2019]GJM02)。
文摘Polymorph screening is currently one of the most important strategies of innovators and generic companies from both pharmaceutical and intellectual property rights perspectives.Different polymorphs may have varying physicochemical properties which influence the bioavailability.The purpose of this study was to investigate the crystal structures and physicochemical properties of Nomegestrol acetate(NOMAC)polymorphs.Forms Ⅰ and Ⅱ(dioxane solvate)were isolated and prepared by systemic crystallization screening in this study,and the forms are reported for the first time.A structural analysis and comparison of all the forms are presented.This study was also the first time to apply a rapid and feasible ultra-highperformance-liquid chromatography(UHPLC)-electrospray ionization(ESI)-tandem mass spectrometry(MS)method to determine plasma levels of NOMAC within 3.0 mins.And this study demonstrated that the optimal crystal Form Ⅰ displayed higher bioavailability than API indicating that Form I could be an alternative solid form that needs further research.
