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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。
Study of tramadol in rat urine in the main metabolites. The healthy rats were injected intraperitoneally with tramadol hydrochloride (9.0 mg.kg-1), and the urine samples were collected from 0 to 36 h. The urine samples were extracted by the solid-phase extraction method and analyzed directly by LC-MSn. Multiple and metabolites were analyzed. By comparing the total ion chromatogram and selected ion monitoring chromatograms of the blank and post-administration urine samples, the chromatograms of three metabolites were compared and the chromatographic retention times, quasi-molecular ions and multi-level fragmentation Ions, a total of 13 metabolites were detected in rat urine samples, including 9 kinds of phase I metabolites, 4 kinds of phase II metabolites, of which 1 was the first metabolite of tramadol found in vivo, which proved that tramadol The major metabolic pathways in rats are O-demethylation, N-demethylation, hydroxylation, N-oxidation and glucuronidation. The LC-MSn method established in this paper can further study tramadol metabolites in other animals and humans.