Mass Spectrometric Structure Elucidation of the Trivalent and Pentavalent Nitrogen Contaminants of Pholcodine in the Cough Relief Medical Form Tuxidrin
International Journal of Analytical Mass Spectrometry and Chromatography
In the paper "Supercritical Fluid Chromatography-Mass Spectrometry (SFC-MS) and MALDI-TOF-MS of Heterocyclic Compounds with Trivalent and Pentavalent Nitrogen in Cough Relief Medical Forms Tuxi and Cosylan" , the presence of morphine and other degradation products of pholcodine in cough relief medical forms of Tuxi are discussed. Tuxi is recalled from the Norwegian market by Weifa pharmaceutical company, and hence it no longer presents problems to users and health authorities there; however,
... ies there; however, the medical form Tuxidrin, which contains a significant amount of pholcodine as the active pharmacological ingredient, is still marketed. In the present paper, Tuxidrin is analyzed to determine the presence of degradation products of pholcodine. The degradation of pholcodine to morphine has been discussed previously as a factor in the development of addiction to narcotics in young persons. The structures of the contaminants in Tuxidrin, such as oxides of pholcodine, are elucidated in the present paper. The toxicity and pharmacology of oxides of alkaloids have generally not been well studied, and very little is known about the toxicity and pharmacology of the degradation (oxidation) products of pholcodine: the N-oxide and the N, N'-dioxide of pholcodine. According to Brondz and Brondz , the N-oxide and possibly also the N, N'-dioxide are less toxic than the original alkaloids and possess greater pharmacological activity, and hence they may be a source of useful new semisynthetic drugs. The question of possible addiction to pholcodine oxides has not been studied, and the potential of these substances to provoke allergies is unclear. The recall of Tuxi from the Norwegian market is mainly based on the fact that pholcodine causes significantly increased levels of IgE antibodies in sensitized patients. Tuxidrin contains pholcodine and has the same negative effect as Tuxi, namely provoking allergies or even anaphylactic shock. From this point of view, Tuxidrin has no advantage over Tuxi. These two medical forms only differ in one respect: Tuxidrin requires a prescription (prescription duty medicine), but Tuxi does not (prescription free medicine). This aspect is also discussed in the present paper.