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

J Pharm Pharmacol. 2000 Jul;52(7):819-29. doi: 10.1211/0022357001774679.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitussive Agents / analysis*
  • Antitussive Agents / chemistry
  • Chloroform / chemistry
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Codeine / analogs & derivatives*
  • Codeine / analysis*
  • Codeine / chemistry
  • Drug Contamination*
  • Mass Spectrometry
  • Morpholines / analysis*
  • Morpholines / chemistry
  • Spectrophotometry, Ultraviolet

Substances

  • Antitussive Agents
  • Morpholines
  • Chloroform
  • pholcodine
  • Codeine