Isolation and identification of three potential impurities of pholcodine bulk drug substance

Three previously unreported manufacturing impurities were isolated from a p holcodine mother liquor using preparative reversed-phase HPLC. The liquor was the residue remaining after recrystallisation of a productio n batch of pholcodine. The impurities, which are structurally related to ph olcodine, were initially detected by thin-layer chromatography (TLC). Their structures were determined after separation by preparative HPLC (Econo-Pre p 5 mu m C18 column, 30cm x 21.2 mm i.d.). Structure elucidation was carrie d out using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscop y (MS) and ultra violet (UV) spectroscopy. The impurities were identified as alkylated derivatives of pholcodine posse ssing second 2-morpholinoethyl substituents at various positions.