Centchroman: in vitro metabolism by rat liver homogenate

Abstract

Centchroman (trans-2,2-dimethyl-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman) (I), a postcoital antifertility agent under clinical development was extensively metabolized by rat liver homogenate in vitro. Employing field desorption mass spectrometry, high performance liquid chromatography, comparison with authentic samples, and studies with 2-¹⁴C-Centchroman, seven metabolites have so far been characterised, which include trans-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman (II, 37.5%), trans-2,2-dimethyl-3-phenyl-4-(p-(β pyrrolidinoethoxy) phenyl)-7-hydroxy chroman (III, 2.5%), β pyrrolidino-ethoxy benzene (IV), 2,2-dimethyl-4-(p-(hydroxy) phenyl)-7-methoxy chromene (V, 39.4%), trans-2,2-dimethyl-3-phenyl-4-(p-(hydroxy) phenyl)-7-methoxy chroman (VI, 5.8%), 2,3-trans-3,4-trans-2-methyl-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chorman (VII, 2.9%), and 2,2-dimethyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman (VIII, 8.8%). Formation of metabolites V and VIII are unusual cases of dephenylation during metabolism.