Photochemical and chemical oxidation of mexiletine and tocainide. Structure elucidation of the major products.
Mexiletine (mex) and tocainide (toc) are antiarrhythmic drugs of closely related structure. Several degradation products are formed by interaction with both light and oxidizing agents in the case of mex, and only by oxidants with toc. On the basis of the identified structures, the decomposition reactions can be classified into two types (Scheme 1). Type I is an oxidative cyclization reaction producing the oxazepine derivative 1 from mex and the diazepine derivative 3 from toc. In reaction type II side chain oxidized products (2 or 4 and 5) are formed. While tocainide.HCl has proved to be photostable, in solid mexiletine HCl the oxazepine derivative was observed after several days' exposure to direct sunlight. The pharmacopoeias (Ph.Eur.3, USP 23), however, do not prescribe light-protection for mex.HCl.
Takács
M
M
Institute of Pharmaceutical Chemistry, Semmelweis University of Medicine, Budapest, Hungary.
Vámos
J
J
Tóth
G
G
Mikó-Hideg
Z
Z
D000889:Anti-Arrhythmia Agents / Q000737:chemistry* / Q000528:radiation effects; D009682:Magnetic Resonance Spectroscopy; D008801:Mexiletine / Q000737:chemistry* / Q000528:radiation effects; D010084:Oxidation-Reduction; D010777:Photochemistry; D016677:Tocainide / Q000737:chemistry* / Q000528:radiation effects
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D016677:Tocainide