Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based Purification Approach.
Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based Purification Approach.
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DOI：
10.3390/molecules22030494
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发表时间：
2017-03-21
期刊：
影响因子：
--
通讯作者：
Fan G
中科院分区：
文献类型：
--
作者：
Zhao X;Jiang J;Yang G;Huang J;Yang G;He G;Chu Z;Hang T;Fan G
吡格雷是由川芎嗪和阿魏酸分子结合而成的新型抗凝血药物。吡格雷对二磷酸腺苷（ADP）诱导的血小板聚集有明显的抑制作用，已获CFDA批准进行I期临床试验。为研究吡格雷静脉给药后在人体尿液中的代谢产物，建立了一种可靠的在线固相萃取-高效液相色谱-串联质谱（SPE-HPLC-MSn）联用方法。初步鉴定了5种代谢产物，提示吡格雷在人体内的主要代谢途径为双键还原、双键氧化，然后是葡萄糖醛酸苷结合。然后采用β-葡糖苷酸水解和大孔树脂纯化方法，然后采用制备高效液相色谱（PHPLC）方法制备两种主要代谢产物，并根据核磁共振（NMR）数据确认其结构。本研究为进一步研究吡格雷的代谢和排泄提供了依据。
Pyragrel, a new anticoagulant drug, is derived from the molecular combination of ligustrazine and ferulic acid. Pyragrel showed significant inhibitory activity against platelet aggregation induced by adenosine diphosphate (ADP), and had been approved for a phase I clinical trial by CFDA. To characterize the metabolites of Pyragrel in human urine after intravenous administration, a reliable online solid-phase extraction couple with high performance liquid chromatography tandem mass spectrometry (online SPE-HPLC-MSn) method was conceived and applied. Five metabolites were detected and tentatively identified, which suggested that the major metabolic pathways of Pyragrel in human were double-bond reduction, double-bond oxidation, and then followed by glucuronide conjugation. Two main metabolites were then prepared using β-glucuronide hydrolysis and macroporous resin purification approach followed by preparative high-performance liquid chromatography (PHPLC) method, with their structures confirmed on the basis of nuclear magnetic resonance (NMR) data. This study provided information for the further study of the metabolism and excretion of Pyragrel.
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影响因子：
3.4
作者：
Lautenschlaeger, Marcus;Lechtenberg, Matthias;Hensel, Andreas
通讯作者：
Hensel, Andreas
影响因子：
3.1
作者：
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影响因子：
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作者：
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DOI：
10.1016/j.jchromb.2013.01.017
发表时间：
2013-03-15
影响因子：
3
作者：
Navarrete, Alicia;Paz Martinez-Alcazar, M.;Garcia, Antonia
通讯作者：
Garcia, Antonia
影响因子：
3
作者：
Alam, Md Ashraful;Sernia, Conrad;Brown, Lindsay
通讯作者：
Brown, Lindsay