双苯氟嗪在大鼠体内的代谢途径

Metabolic pathways of dipfluzine in rats

目的 研究双苯氟嗪在大鼠体内的代谢途径。方法 大鼠ig双苯氟嗪,LC/DAD/MS法分离、鉴定尿中代谢产物。结果 在大鼠尿中有 1 -(4 氟苯基 ) 4 哌嗪基丁酮及其葡糖醛酸结合物、4 羟基二苯甲酮及其葡糖醛酸结合物、4 -氟 -γ- 羟基苯丁酸及其葡糖醛酸和硫酸结合物、二苯甲醇及其葡糖醛酸结合物和双苯氟嗪,二苯甲酮。结论双苯氟嗪在大鼠体内主要经哌嗪环 -1- 和 -4- 氮脱烷基代谢,部分代谢物再与葡糖醛酸和 /或硫酸结合。

Aim To investigate the metabolic pathways of dipfluzine in rats. Methods After an oral dose of dipfluzine (80 mg·kg-1) to rats, urine was collected for 12 h. The metabolites of dipfluzine in urine were chromatographed and identified by LC/DAD/MS methods. Results In the rat urine, there were 1-(4-fluorophenyl)-4-piperazinylbutanone and its glucuronide, 4-hydroxybenzophenone and its glucuronide, 4-fluoro-γ-hydroxybenzenebutanoic acid and its glucuronide and sulfate, diphenylmethanol and its glucuronide, dipfluzine, and benzophenone. Conclusion In rats, dipfluzine was mainly metabolized in the pathways of N-desalkylation at 1- and 4-positions of piperazine ring. Some of metabolites were further conjugated with glucuronic acid and/or sulfuric acid.