用固相萃取-核磁共振氢谱法研究大鼠尿液中R-(-)-布洛芬光活代谢产物

目的　用固相萃取-核磁共振氢谱法研究大鼠尿液中R-(-)-布洛芬代谢产物及异构体的转化。方法　将服用R-(-)-布洛芬后0～24 h大鼠尿液经固相萃取柱处理、核磁共振氢谱测定代谢产物的结构。结果　尿液中含有4个主要代谢产物：2＇-羟基-布洛芬及其葡糖苷酸结合物、1＇-羧基-布洛芬葡糖苷酸和布洛芬葡糖苷酸。后两者为非对映异构体混合物。结论　R-(-)-布洛芬在大鼠体内发生了异构体转化，异丁基侧链中末端甲基的氧化代谢具有立体选择性。

USE OF HIGH-FIELD NULEAR MAGNETIC RESONANCE SPECTROSCOPY FOR THE ANALYSIS OF STEREOSELECTIVE METABOLITES OF IBUPROFEN (R)-ENANTIOMER IN RAT URINE

AIM: To study the metabolic chiral inversion and chiral metabolites of R-(-)-ibuprofen. METHODS: Following administration of R-(-)-ibuprofen (250 mg.kg-1), analysis was performed on rat urine purified extracts obtained by solid phase extraction onto C-18 bonded silica gel, then the metabolites of ibuprofen were detected and identified by 1HNMR spectroscopy. RESULTS: Except for a little ibuprofen, there were 2'-hydroxy-ibuprofen and its glucuronide, 1'-carboxy-ibuprofen glucuronide and ibuprofen glucuronide in rat urine. 2'-hydroxy-ibuprofen is the main metabolite. 1'-carboxy-ibuprofen glucuronide and ibuprofen glucuronide were diastereoisomers. CONCLUSION: There was the phenomenon of metabolic chiral inversion, whereby the R-enantiomer is transformed in vivo to its active S-antipode via an unusual process.