鹿 慧 吴 迪 严 静 曾 琴 吴艳平 孙 璐. LC-MSn法研究曲马多在大鼠尿中的代谢产物J. 药学学报, 2011,46(8): 968-975.
引用本文: 鹿 慧 吴 迪 严 静 曾 琴 吴艳平 孙 璐. LC-MSn法研究曲马多在大鼠尿中的代谢产物J. 药学学报, 2011,46(8): 968-975.
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LU Hui, Tun- Di, Yan- Jing, Ceng- Qin, Tun-Yan-Beng, Sun- Lu. Analysis of primary metabolites of tramadol in rat urine by LC-MSnJ. 药学学报, 2011,46(8): 968-975.
Citation: LU Hui, Tun- Di, Yan- Jing, Ceng- Qin, Tun-Yan-Beng, Sun- Lu. Analysis of primary metabolites of tramadol in rat urine by LC-MSnJ. 药学学报, 2011,46(8): 968-975.
shu

LC-MSn法研究曲马多在大鼠尿中的代谢产物

Analysis of primary metabolites of tramadol in rat urine by LC-MSn

    摘要
  • 摘要:

    研究曲马多在大鼠尿中的主要代谢产物。健康大鼠腹腔注射盐酸曲马多 (剂量为9.0 mg·kg−1), 收集0～36 h不同时间段的尿样, 经固相萃取法预处理后, 直接采用LC-MSn法对曲马多和代谢产物进行分析。通过比较空白尿样和给药后尿样的总离子流色谱图和选择离子监测色谱图, 与3个代谢产物对照品比较, 并分析各个色谱峰的色谱保留时间、准分子离子和多级碎片离子, 在大鼠尿样中共检测到13种代谢产物, 包括9种I相代谢产物, 4种II相代谢产物, 其中1种为首次在生物体内发现的曲马多代谢产物, 证明曲马多在大鼠体内的主要代谢途径为O-去甲基化、N-去甲基化、羟基化、N-氧化和葡糖醛酸化反应。本文所建立的LC-MSn方法可进一步研究曲马多在其他动物和人体内的代谢产物。

     

    Abstract:

    Tramadol and its metabolites in rat urine were identified by LC-MSn.  Rat urine samples of 0−36 h were collected after ip 9.0 mg·kg−1 tramadol, then the samples were enriched and purified through solid- phase extraction cartridge.  Purified samples were analyzed by LC-MSn.  Possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks and analyzing the retention time, quasi-molecular ion and fragment ion of all chromatograms.  Nine phase I metabolites and four phase II metabolites were identified in rat urine.  One of the metabolites was found first time in living body.  The metabolites were formed via the following metabolic pathways: O-demethylation, N-demethylation, hydroxylation, N-oxidation and conjugation.  The method can be used to identify tramadol and its metabolites in other animals and human.

     

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