The Production of Amitriptyline from Nortriptyline in Formaldehyde-Containing Solutions

Abstract

The stability of nortriptyline in aqueous solutions containing various concentrations of formaldehyde was investigated. Amitriptyline, as a reaction product, was determined by gas chromatography/mass spectrometry (GC/MS) in these experiments. Factors that may contribute to this phenomenon, including pH, formaldehyde concentration, and incubation time were evaluated. At 40% (v/v) formaldehyde concentration and pH 4, there was a 68% decrease in nortriptyline concentration along with a concomitant formation of amitriptyline after 24 h. The N-methylated product was responsible for 48% of the total tricyclic drug present. The data also clearly indicate that the formation of amitriptyline is favored at elevated pH.

Pitfalls in forensic toxicology

“…Embalming¯uid also usually contains formaldehyde and alcohols and the conversion of nortriptyline to amitriptyline has been described in embalmed bodies. 27 In the laboratory Accidental contamination of specimens with drugs from stock solutions of calibrators, which usually have very high concentrations, is always a possibility. Splashes, drops and the re-use of pipette tips are all potential means of contamination and should be guarded against.…”

Toxicological analysis of drugs and poisons in formalin-fixed organ tissues

“…Several studies of the analysis of embalmed and/or formalin-fixed organ tissues for several drugs and poisons: phenobarbital [12]; ethchlorvynol [13]; paraquat [6]; diazepam, phenytoin, desipramine and phenobarbital [14]; amitriptyline and nortriptyline [4]; malathion [11] and tricyclic antidepressants (amitriptyline, nortriptyline, imipramine and desipramine) [15] have been reported. To the best of our knowledge, however, there are hardly any published reports of analytical studies on illicit methamphetamine, amphetamine, narcotics, cannabinoids, some psychotropic drugs and components of thinners in formalinfixed organ tissues.…”

Issues Affecting Interpretation: Stability and Artefacts

“…49.1). For example, methylation of nortriptyline to amitriptyline occurs during formalin fixation and storage (Dettling et al 1990). Methylation has also been observed with amphetamine-type drugs, barbiturates, benzodiazepines and fenfluramine (Gannett et al 2001b;Tracy et al 2001;Cingolani et al 2005;Tirumalai et al 2005).…”