Impurity profile study of dutasteride

During the process development of dutasteride in the laboratory analysis showed some impurity peaks in HPLC ranging from 0.05 to 0.1%. The same samples were analyzed by LCMS method and identified peak at m/z 508 (desmethyl dutasteride), 530 (dihydro dutasteride) and 528 (isomer of dutasteride). These impurities were synthesized individually and characterized based on the spectroscopic data (HPLC, IR, NMR and MS). The structures of these impurities were 17β-N-[2,5-bis(trifluoromethyl) phenyl]carbamoyl-3-hydroxyl-4-azaestra-1,3,5,7,9-pentaene (desmethyl of dutasteride 2), 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbamoyl-4-aza-5α-androstane-3-one (dihydro impurity of dutasteride 3), and 17β-N-[2,5-bis(trifluoromethyl) phenyl] carbamoyl-4-aza-5β-androst-1-ene-3-one (β-isomer of dutasteride 4), respectively. The formation and synthesis of dutasteride impurities are discussed.