YK- 1101, with its structure as S-（（E）-4-（（7S, 10S,Z）-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 （17）, 15（ 18）-dien- 10-yl）but-3-en- 1 -y l） ...YK- 1101, with its structure as S-（（E）-4-（（7S, 10S,Z）-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 （17）, 15（ 18）-dien- 10-yl）but-3-en- 1 -y l） ethanethioate, is synthesized as a potential histone deacetylase inhibitor. Its quality and stability under various stress conditions are not fully understood. In this study, a high performance liquid chromatographic （HPLC） method was established and validated for the analysis of YK-1101 bulk drug samples. The chromatographic separation was performed on a C18 column with acetonitrile and water as mobile phase in a gradient elution. Based on the established method, the stability studies of YK-1101 under various stress conditions were carried out. YK-1101 was shown to undergo degradation under basic and acidic stress conditions, while it was stable under oxidative, photolytic and thermal conditions. In addition~ a time of flight mass spectrometer （TOF/MS） was coupled to HPLC for the characterization of major degradation products produced under basic and acidic stress conditions. Their degradation pathways were also discussed.展开更多
基金supported by the postgraduate innovation foundation of Simcere (No. CX11S-002XS)
文摘YK- 1101, with its structure as S-（（E）-4-（（7S, 10S,Z）-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 （17）, 15（ 18）-dien- 10-yl）but-3-en- 1 -y l） ethanethioate, is synthesized as a potential histone deacetylase inhibitor. Its quality and stability under various stress conditions are not fully understood. In this study, a high performance liquid chromatographic （HPLC） method was established and validated for the analysis of YK-1101 bulk drug samples. The chromatographic separation was performed on a C18 column with acetonitrile and water as mobile phase in a gradient elution. Based on the established method, the stability studies of YK-1101 under various stress conditions were carried out. YK-1101 was shown to undergo degradation under basic and acidic stress conditions, while it was stable under oxidative, photolytic and thermal conditions. In addition~ a time of flight mass spectrometer （TOF/MS） was coupled to HPLC for the characterization of major degradation products produced under basic and acidic stress conditions. Their degradation pathways were also discussed.
