Stability of Tricyclic Antidepressants in Formalin Solutions

Abstract

We investigated the stability of the secondary amines, desipramine (DP) and nortriptyline (NRT), and the tertiary amines, imipramine (IP) and amitriptyline (AT), in formaldehyde (F) and paraformaldehyde (PF) aqueous solutions. NRT showed little instability in 0.37 to 37% F and PF solutions, but AT formation was detected and increased, up to 0.46 to 2.7%, in parallel with rising F and PF concentrations. DP was unstable and levels decreased to 74 to 96% with increasing F concentrations, and fell only to 96% in 10% PF solution. IP formation increased in the same manner as AT to 2.9 to 3.5% of the initial DP. When AT and IP were stored in F and PF solutions, concentrations of AT and IP did not change. DP in F pH 3 to 11 phosphate buffer (PB) solutions showed high recovery in the order: pH 5 > pH 7 > pH 9 > pH 3 and pH 11. DP in PF buffered solutions decreased slightly only at pH 3 (3.5%). By contrast, IP did not change at any pH (pH 3 to 11) of the F or PF solutions. During storage for 21 days at room temperature in 3.7% F and PF solutions, IP and DP degradation was accelerated when compared with the values in pH 3 and 7 PB solutions. However, IP detected in DP F or PF solution was only 0.2% of the initial DP 21 days after storage. Thus, AT, NRT, IP and DP degraded gradually in F and PF solutions during storage at room temperature. TCAs may first react nucleophilically with formaldehyde to form hemiaminals. DP in 3.7% formaldehyde aqueous solution formed little of its methylated product, IP, at room temperature.