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New forced degradation products of vildagliptin: Identification and structural elucidation using LC-MS, with proposed formation mechanisms
Journal of Liquid Chromatography & Related Technologies ( IF 1.0 ) Pub Date : 2020-06-16 , DOI: 10.1080/10826076.2020.1779084
Sharif Arar 1 , Enas Al-Qudah 1 , Muhammad Alzweiri 2 , Kamal Sweidan 1
Affiliation  

Abstract A new and simple RP-HPLC-UV method was developed for well-separation of vildagliptin raw material and its degradation products at different conditions; it uses of ammonium acetate buffer at pH= 7.5 and methanol with Athena C18 -WP (250 mm) column. Results show that six degradants have been identified using LC–MS technique, in addition to the NMR approach in some cases. One degradant at relative retention time (RRT) 1.3 was formed under acidic condition and designated as 2-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) hexahydropyrrolo[1,2-a]pyrazine-1,4-dione at m/z = 304. Three degradants were formed under various conditions of basic hydrolysis at RRTs 1.2, 0.6 and 0.4 with following names and molar masses (m/z), respectively: 1-(((1S, 3S, 5S, 7S)-1,3-dihydroxyadamantan-2-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 337.2, 1-(((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 321.1 and (1,4-dioxo-1,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-3-yl)glycylproline at m/z = 322.6. Another three degradants were also formed under oxidative oxidations of vildagliptin, one at RRT 0.38 and designated as N-hydroxy-N-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) glycinate with m/z 241.1, the second one was identical to that formed under basic hydrolysis at RRT 0.6 and the last one has RRT 0.8 and was identified as (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol at m/z 183.1. Formation mechanisms for the degradation products were described. Graphical Abstract

中文翻译:

维格列汀的新强制降解产物:使用 LC-MS 进行鉴定和结构解析,并提出形成机制

摘要 建立了一种新的、简单的RP-HPLC-UV方法,用于在不同条件下对维格列汀原料及其降解产物进行良好的分离;它使用 pH= 7.5 的醋酸铵缓冲液和甲醇与 Athena C18 -WP (250 mm) 色谱柱。结果表明,除了在某些情况下使用 NMR 方法外,还使用 ​​LC-MS 技术鉴定了六种降解物。在酸性条件下形成了相对保留时间 (RRT) 1.3 的一种降解物,命名为 2-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) hexahydropyrrolo[1,2-a]pyrazine-1 ,4-二酮,m/z = 304。在 RRT 为 1.2、0.6 和 0.4 的各种碱性水解条件下形成了三个降解物,分别具有以下名称和摩尔质量 (m/z):1-(((1S, 3S , 5S, 7S)-1,3-二羟基金刚烷-2-基)甘氨酰)吡咯烷-2-甲酰胺,m/z = 337.2, 1-(((1R, 3S, 5R, 7S)-3-羟基金刚烷-1-基)glycyl)pyrrolidine-2-carboxamide 在 m/z = 321.1 和 (1,4-dioxo-1,4,6,7,8,8a-六氢吡咯并[1,2- a]吡嗪-3-基)甘氨酰脯氨酸,m/z = 322.6。在维格列汀的氧化氧化下也形成了另外三种降解物,一种在 RRT 为 0.38 时被命名为 N-羟基-N-((1R, 3S, 5R, 7S)-3-羟基金刚烷-1-基) 甘氨酸盐,m/z 241.1 ,第二个与在 RRT 0.6 的碱性水解下形成的相同,最后一个的 RRT 为 0.8,在 m/z 下被鉴定为 (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol 183.1. 描述了降解产物的形成机制。图形概要 在维格列汀的氧化氧化下也形成了另外三种降解物,一种在 RRT 为 0.38 时被命名为 N-羟基-N-((1R, 3S, 5R, 7S)-3-羟基金刚烷-1-基) 甘氨酸盐,m/z 241.1 ,第二个与在 RRT 0.6 的碱性水解下形成的相同,最后一个的 RRT 为 0.8,在 m/z 下被鉴定为 (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol 183.1. 描述了降解产物的形成机制。图形概要 在维格列汀的氧化氧化下也形成了另外三种降解物,一种在 RRT 为 0.38 时被命名为 N-羟基-N-((1R, 3S, 5R, 7S)-3-羟基金刚烷-1-基) 甘氨酸盐,m/z 241.1 ,第二个与在 RRT 0.6 的碱性水解下形成的相同,最后一个的 RRT 为 0.8,在 m/z 下被鉴定为 (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol 183.1. 描述了降解产物的形成机制。图形概要 描述了降解产物的形成机制。图形概要 描述了降解产物的形成机制。图形概要
更新日期:2020-06-16
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