盐酸丁咯地尔在人血浆和肝微粒体中代谢产物鉴定

发布时间：2018-03-25 01:15

本文选题：盐酸丁咯地尔　切入点：人　出处：《沈阳药科大学学报》2017年08期

【摘要】：目的研究盐酸丁咯地尔在人体的代谢情况。方法采用UPLC-QTOF/MS法发现并鉴定盐酸丁咯地尔在人血浆和肝微粒体孵化体系中的代谢产物。采用HSS T3 C18色谱柱(100 mm×2.1 mm,1.8μm),以5 mmol·L~(-1)醋酸铵水溶液(含体积分数0.05%的甲酸)(A)-甲醇(B)为流动相梯度洗脱,流速为0.4 m L·min~(-1),采用ESI离子源,正离子模式下检测。结果通过与空白生物样品进行比较,在人血浆和肝微粒体中共发现了丁咯地尔及其24种代谢产物,其中18种为首次发现的代谢产物。根据代谢产物的色谱保留时间、准分子离子及碎片离子等信息,确定并推断了丁咯地尔及其代谢产物的结构,阐明了丁咯地尔在人体的代谢途径,包括去甲基化、氧化、羟基化、硫酸和葡萄糖醛酸结合途径。结论建立了UPLC-QTOF/MS方法研究了丁咯地尔在人体的代谢情况,为其化学结构类似药物和候选化合物的代谢研究提供依据。
[Abstract]:Objective to study the metabolism of buflomedil hydrochloride in human body. Methods the metabolites of buflomedil hydrochloride in human plasma and liver microsomal incubation system were found and identified by UPLC-QTOF/MS method. HSS T3 C18 column was used to determine the metabolism of buflomedil hydrochloride in human plasma and liver microsomal incubation system. The mobile phase gradient elution of ammonium acetate aqueous solution (0.05% formic acid-methanol-B). Results buflomedil and its 24 metabolites were found in human plasma and liver microsomes by ESI ion source and positive ion mode. According to the chromatographic retention time of metabolites, excimer ions and fragment ions, the structure of buflomedil and its metabolites was determined and inferred. The metabolic pathways of buflomedil in human body, including demethylation, oxidation, hydroxylation, combination of sulfuric acid and glucuronic acid, were elucidated. Conclusion UPLC-QTOF/MS method was established to study the metabolism of buflomedil in human body. It provides a basis for the study of metabolism of similar drugs and candidate compounds.
【作者单位】：沈阳药科大学药学院;
【基金】：辽宁省教育厅项目(L2014390) 沈阳药科大学中青年教师中长期培养计划项目(ZQN2015007)
【分类号】：R96

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