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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。
After gavage with healthy beagle dog ranolazine (30 mg.kg 1), urine samples were collected at different time points. C18 column solid phase extraction (LC-MSn) was used to determine ranolazine and metabolites in beagle dog urine Determination. By comparison with ranolazine and its three metabolites control samples, the total ion chromatogram and the selected ion monitoring chromatogram of blank urine samples and post-administration urine samples were compared and the retention time of each chromatographic peak was analyzed. Excimer ions And multistage fragment ions, 31 metabolites including 17 phase I metabolites and 14 phase II metabolites were detected in Beagle dog urine samples, of which 16 were the first metabolites of ranolazine found in vivo. The results showed that the main metabolites of ranolazine in Beagle dogs were O-demethylation, O-dearyllation, hydroxylation, N-alkylation, amide hydrolysis, glucuronidation and sulfation. This study provides a reliable analytical method and research direction for further studying the metabolism of ranolazine in the human body.