Instability of Amitriptyline Base

Abstract

AMITRIPTYLINE hydrochloride is an antidepressant which produces mild tranquillizing side effects (Fig. 1a). During an investigation into a death caused by the ingestion of amitriptyline it was noticed that the free base, a colourless oil prepared from a tablet for reference purposes, became yellow on standing. Thin-layer chromatography (silica gel G.F.; methanol: acetone 1 : 1 v/v) showed that the yellow material travelled further than the free base and unlike the base showed no colour reaction with potassium iodoplatinate. Gas liquid chromatography of the fresh base showed a single peak. On standing for 2 days, a second peak appeared, presumably corresponding to the yellow breakdown product. Some of this yellow compound was separated by thin-layer chromatography and analysed by infrared spectrophotometry. Comparison between the spectrum of the impurity and that of the pure base suggested that the aliphatic double bond had been oxidized to yield a ketonic product. The strong aliphatic–N–(CH₃)₂ stretching frequencies at 2,760 and 2,800 cm⁻¹ were absent and there was an increase in the relative intensities of aromatic over aliphatic bands.