Isolation and identification of three potential impurities of pholcodine bulk drug substance.
Three previously unreported manufacturing impurities were isolated from a pholcodine mother liquor using preparative reversed-phase HPLC. The liquor was the residue remaining after recrystallisation of a production batch of pholcodine. The impurities, which are structurally related to pholcodine, were initially detected by thin-layer chromatography (TLC). Their structures were determined after separation by preparative HPLC (Econo-Prep 5 microm C18 column, 30 cm x 21.2 mm i.d.). Structure elucidation was carried out using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and ultra violet (UV) spectroscopy. The impurities were identified as alkylated derivatives of pholcodine possessing second 2-morpholinoethyl substituents at various positions.
Department of Pharmaceutical Sciences, University of Strathclyde Institute of Biomedical Sciences (SIBS), Glasgow, Scotland, UK.
O M
OM
Denk
A I
AI
Gray
G G
GG
Skellern
D G
DG
Watson
D000996:Antitussive Agents / Q000032:analysis* / Q000737:chemistry; D002725:Chloroform / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003061:Codeine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry; D004340:Drug Contamination; D013058:Mass Spectrometry; D009025:Morpholines / Q000032:analysis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D000996:Antitussive Agents; D009025:Morpholines; D002725:Chloroform; C008872:pholcodine; D003061:Codeine