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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。
Objective To study the metabolism of buflomedil hydrochloride in the human body. Methods The metabolites of buflomedil hydrochloride in human plasma and liver microsomal incubation system were identified and identified by UPLC-QTOF / MS. Using 5 mmol·L -1 ammonium acetate aqueous solution (containing 0.05% formic acid) (A) -methanol (B) as mobile phase on HSS T3 C18 column (100 mm × 2.1 mm, 1.8 μm) Gradient elution at a flow rate of 0.4 m L · min -1 using ESI ion source and positive ion mode. RESULTS By comparison with blank biological samples, buflomedil and its 24 metabolites were found in human plasma and liver microsomes, of which 18 were the first-identified metabolites. The structure of buflomedil and its metabolites was identified and deduced from the information of chromatographic retention times, quasi- and quasaron ions of the metabolites, and elucidated the metabolic pathway of buflomedil in the human body, including demethylation, Oxidation, hydroxylation, sulfate and glucuronidation pathways. Conclusion The UPLC-QTOF / MS method was developed to study the metabolism of buflomedil in the human body and provided the basis for the study on the metabolism of similar drugs and candidate compounds.