唐静雅, 王 薇, 李 黎, 张纯刚, 王迪敏, 孙 璐. LC-MSn法研究雷诺嗪在比格犬尿中的主要代谢物J. 药学学报, 2012,47(8): 1031-1038.
引用本文: 唐静雅, 王 薇, 李 黎, 张纯刚, 王迪敏, 孙 璐. LC-MSn法研究雷诺嗪在比格犬尿中的主要代谢物J. 药学学报, 2012,47(8): 1031-1038.
shu
TANG Jing-ya, WANG Wei, LI Li, ZHANG Chun-gang, WANG Di-min, SUN Lu. Analysis of primary metabolites of ranolazine in dog urine by LC-MSnJ. 药学学报, 2012,47(8): 1031-1038.
Citation: TANG Jing-ya, WANG Wei, LI Li, ZHANG Chun-gang, WANG Di-min, SUN Lu. Analysis of primary metabolites of ranolazine in dog urine by LC-MSnJ. 药学学报, 2012,47(8): 1031-1038.
shu

LC-MSn法研究雷诺嗪在比格犬尿中的主要代谢物

Analysis of primary metabolites of ranolazine in dog urine by LC-MSn

    摘要
  • 摘要:

    灌胃给予健康比格犬雷诺嗪 (30 mg·kg−1) 后, 收集不同时段的尿样, 经C18小柱固相萃取, 采用LC-MSn法对比格犬尿样中雷诺嗪和代谢物进行测定。通过与雷诺嗪及其3个代谢物对照品比较, 将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比较, 并分析各个色谱峰的保留时间、准分子离子和多级碎片离子, 在比格犬尿样中共检测到31种代谢物, 包括17种I相代谢物和14种II相代谢物, 其中16种为首次在生物体内发现的雷诺嗪代谢物。结果表明, 雷诺嗪在比格犬体内的主要代谢途径为O-去甲基化、O-去芳基化、羟基化、N-去烷基化、酰胺水解、葡糖醛酸化和硫酸化。为深入研究雷诺嗪在人体内的代谢情况提供了可靠的分析方法和研究方向。

     

    Abstract:

    Ranolazine and metabolites in dog urine were identified by LC-MSn.  Dog urine samples were collected after ig 30 mg·kg−1 ranolazine, then the samples were enriched and purified through solid-phase extraction cartridge.  The purified samples were analyzed by LC-MSn .  The possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks.  Seventeen phase I metabolites and fourteen phase II metabolites were identified in dog urine.  Three metabolites were identified by comparing with the control article.  The metabolites were formed via the following metabolic pathways: O-demethylation, O-dearylation, hydroxylation, N-dealkylation, amide hydrolysis, glucuronidation and sulfation.  The LC-MSn method is suitable for the rapid identification of drug and its metabolites in biologic samples.

     

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