| 谷元,司端运.粉防己碱在大鼠体内的代谢途径研究[J].济宁医学院学报,2012,(5):306-311 |
| 粉防己碱在大鼠体内的代谢途径研究 |
| Study on the metabolic pathway of tetrandrine in rats in vivo |
| 投稿时间：2012-09-25 |
| DOI：10.3969/j.issn.1000-9760.2012.05.001 |
| 中文关键词: 粉防己碱;代谢产物;大鼠 |
| 英文关键词: Tetrandrine;Metabolite;Rat urine |
| 基金项目:国家重大专项资助(2009ZX09304005;2012ZX09506001) |
| 作者 | 单位 | | 谷元 | 天津药物研究院, 释药技术与药代动力学国家重点实验室, 天津 300193 | | 司端运 | 天津药物研究院, 释药技术与药代动力学国家重点实验室, 天津 300193 |
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| 中文摘要: |
| 目的 研究双苄基异喹啉类生物碱药物粉防己碱在大鼠体内的代谢途径。方法 大鼠灌胃50 mg/kg粉防己碱后,收集0~24 h尿样,应用UPLC-MS法对粉防己碱在大鼠尿中的代谢产物进行鉴定,从而进一步分析在大鼠体内的代谢产物。结果 在大鼠尿中共检测到14个可能的代谢产物,其中7个代谢产物属于首次发现。主要的代谢途径包括N-去甲基化、O-去甲基化、芳环碳羟基化、脂肪碳羟基化、N-氧化等。结论 粉防己碱在大鼠体内经历了广泛代谢,UPLC-MS法具有较高的分离度以及简化的质谱图,为粉防己碱代谢产物的鉴定提供了有效的检测手段。 |
| 英文摘要: |
| Objective The objective of this study is to investigate metabolism of tetrandrine, a bis-benzylisoquinoline alkaloid isolated from the root of Stephania tetrandra S.Moore of the Menispermaceae, in rat urine by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS).Methods After oral administration of 50 mg/kg tetrandrine to rat, urine samples were collected and pretreated by direct protein precipitation with methanol for UPLC-MS analysis.The structure of the metabolites was elucidated by comparing the changes of molecular masses(△M), retention times and MS2 spectral patterns of metabolites with those of parent drug.Results Fourteen metabolites were detected and characterized by UPLC-MS/MS in rat urine, and seven metabolites were found for the first time.Tetrandrine metabolites were mainly formed via two main pathways:demethylation(N-demethylation and O-demethylation) and isoquinoline ring oxidation(hydroxy-tetrandrine and oxo-tetrandrine).Conclusion The rapid UPLC/MS/MS is a powerful approach for detecting and identifying metabolites in complex biological matrix with high speed and sensitivity, good resolution and simplified MS spectra. |
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