Degradation Pathway of Pralidoxime Chloride in Concentrated Acidic Solution

• Published in: Journal of pharmaceutical sciences 1986-06, Vol.75 (6), p.608-611
• Main Authors: Fyhr, Peter, Brodin, Arne, Ernerot, Lennart, Lindquist, Jörgen
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Hydrogen-Ion Concentration; Medical sciences; Pesticides, fertilizers and other agrochemicals toxicology; Pralidoxime Compounds - analysis; Solutions; Spectrophotometry, Ultraviolet; Toxicology
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600750618

The degradation products of pralidoxime chloride (1) (X−=Cl−) in concentrated aqueous solutions (≤50% w/v) were identified using one or more methods: HPLC, polarography, voltammetry, MS and/or NMR. The products found were the 2-cyano-, 2-carboxamido-and 2-carboxy-1-methyl-pyridinium chlorides, 1-methyl pyridinium chloride, cyanide ion, ammonia and carbon dioxide. 1-Methyl-2-pyridone was indirectly identified by the presence of cyanide ion. The degradation rate increased with increasing pH values between pH 1 and 3.2 and with increasing concentrations between 1 and 50% w/v pralidoxime chloride. The results suggest that 1 (X−=Cl−) is dehydrated by a hydroxyl-ion catalyzed reaction to the nitrile 2which is hydrolyzed to either the pyridone 6 and cyanide ion or to 2-carboxamido-1-methyl-pyridinium chloride 3. The amide is hydrolyzed to give the 2-carboxy derivative 4 which finally is decarboxylated to give 1 -methylpyridinium chloride 5.