手性流动相添加剂法测定5－（对－羟基苯基）－5－苯基乙内酰脲的体外代谢的立体选择性

DETERMINATION OF STEREOSELECTIVITY IN 5-(p-HYDROXYPHENYL)-5-PHENYLHYDANTOIN GLUCURONIDES FORMATION BY CHIRAL MOBILE PHASE ADDITIVE METHOD

作者研究了５－（对－羟基苯基）－５－苯基乙内酰脲（ｐ－ＨＰＰＨ）体外形成葡萄糖醛酸甙的立体选择性。以β－环糊精为手性流动相添加剂，反相高效液相法测定底物Ｓ－和Ｒ－ｐ－ＨＰＰＨ的消失量。结果显示，在苯巴比妥（ＰＢ）和β－萘黄酮（β－ＮＦ）诱导的鼠肝微粒体中，Ｒ－ｐ－ＨＰＰＨ形成葡萄糖醛酸甙较Ｓ－ｐ－ＨＰＰＨ快，尤其是β－ＮＦ诱导的微粒体，反应液中Ｓ－／Ｒ－浓度比值由起始时１．０，经反应５０ｍｉｎ后上升到１．８５；而ＰＢ诱导的微粒体，经５０ｍｉｎ反应后，Ｓ－／Ｒ－浓度比值为１．０９。这一结果表明，β－ＮＦ诱导的鼠肝微粒体对Ｒ－ｐ－ＨＰＰＨ葡萄糖醛酸甙的形成，具有显著的立体选择性。

This paper reports the stereoselectivity in 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) glucuronides formation in vitro. The concentration of S-and R-p-HPPH in rat liver microsomes was determined by RP-HPLC with β-cycledextrin as a chiral mobile phase additive. R-p-HPPH gulcuronide formed faster than S-p-HPPH gulcuronide in the PB or β-NF-induced rat liver microsomes. The microsomes induced by β-NF enhanced p-HPPH glucuronide formation,specially in R-p-HPPH. The S-/R-concentration ratios rose from 1. 00 to 1. 85 with the increase in incubation duration(0～50min) in the β-NFinduced microsomes ,whereas the S-/R-ratios remained constant in the PB-induced microsomes. The result indicates that the reaction of p-HPPH glucuronides formation is stereoselective in the β-NF-induced microsomes.