The production of amitriptyline from nortriptyline in formaldehyde-containing solutions

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.