Characterization of the synthesis of N,N‐dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry

An impurity profile was established for a synthetic route to the hallucinogen N,N-dimethyltryptamine (DMT) using reductive amination of tryptamine with formaldehyde and reduction by sodium cyanoborohydride. Seven compounds were detected and quantified, including DMT and several byproducts. Replacing sodium cyanoborohydride with sodium borohydride almost exclusively produced tetrahydro-β-carboline instead of DMT. Detection limits ranged from 21.5 to 87.7 ng mL⁻¹, and quantification limits from 24.6 to 88.3 µg mL⁻¹, with linearity from 20.8 to 980 µg mL⁻¹. The method is useful for forensic and pharmaceutical analysis of DMT.

Study at a glance

Abstract

The present study established an impurity profile of a synthetic route to the hallucinogenic N,N-dimethyltryptamine (DMT). The synthesis was carried out under reductive amination conditions between tryptamine and aqueous formaldehyde in the presence of acetic acid followed by reduction with sodium cyanoborohydride. Analytical characterization of this synthetic route was carried out by gas chromatography ion trap mass spectrometry using electron- and chemical-ionization modes. Methanol was employed as a liquid CI reagent and the impact of stoichiometric modifications on side-products formation was also investigated. Tryptamine 1, DMT 2, 2-methyltetrahydro-β-carboline (2-Me-THBC, 3), N-methyl-N-cyanomethyltryptamine (MCMT, 4), N-methyltryptamine (NMT, 5), 2-cyanomethyl-tetrahydro-β-carboline (2-CM-THBC, 6) and tetrahydro-β-carboline (THBC, 7) have been detected under a variety of conditions. Replacement of formaldehyde solution with paraformaldehyde resulted in incomplete conversion of the starting material whereas a similar replacement of sodium cyanoborohydride with sodium borohydride almost exclusively produced THBC instead of the expected DMT. Compounds 1 to 7 were quantified and the limits of detection were 28.4, 87.7, 21.5, 23.4, 41.1, 36.6, and 34.9 ng mL(-1), respectively. The limits of quantification for compounds 1 to 7 were 32.4, 88.3, 25.4, 24.6, 41.4, 39.9, and 37.0 µg mL(-1), respectively. Linearity was observed in the range of 20.8-980 µg mL(-1) with correlation coefficients > 0.99. The application holds great promise in the area of forensic chemistry where development of reliable analytical methods for the detection, identification, and quantification of DMT are crucial and also in pharmaceutical analysis where DMT might be prepared for use in human clinical studies.