Abstract

Abstract The resolving power of high pressure liquid chromatography has been combined with the sensitivity of electrochemical oxidation to develop a method for determination of codeine and its metabolites, morphine and norcodeine, in plasma. Plasma samples containing Internal Standard (Dihydromorphinone) are extracted at pH 8.9 into a 2/98 v/v/ Butanol/methyl tertiary butyl ether organic solvent system and back extracted into 25 mM phosphate buffer pH 2.8. The optimal recovery is greater than 90% for codeine and 70% for morphine and norcodeine. Reverse phase chromatography (5 micrometer phenyl column) with detection by electrochemical oxidation at + 1.2 V vs. Ag/AgCl is utilized. The method is sensitive, specific and precise. This method is used to establish a concentration - time profile for plasma codeine and morphine from a human volunteer after a 60 mg oral dose of codeine phosphate. No measurable concentration of norcodeine was found in the plasma. Codeine has long been used as an analgesic and antit...

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