N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation

Figures & data

Table 1. Average half-life of DMT after incubation with human liver microsomes in the absence or presence of different enzyme inhibitors.

Inhibitor	Half-life (min)
No inhibitor	11.3
Harmine	NA
Quinidine	11.6
SKF-525A	24.2

Harmine: MAO-A inhibitor; Quinidine: CYP2D6 inhibitor; SKF-525A: general CYP-enzyme inhibitor; NA: not applicable

Figure 1. Combined extracted chromatogram of detected metabolites at different time points after incubation of DMT with CYP2D6.

Figure 2. Signal response of DMT and the four major metabolites over time after incubation of DMT with CYP2D6.

Table 2. Proposed formula, transformation, retention time (RT), mass of molecular ion and mass error (ppm) of DMT and metabolites after incubation with CYP2D6.

ID	Proposed formula	Transformation	RT (min)	m/z	ppm
M1	C12H16N2O3	Tri-oxygenation (+3 O)	1.30	237.1230	−1.4
M2	C12H16N2O2	Di-oxygenation (+2 O)	3.25	221.1281	−1.5
M3	C12H16N2O2	Di-oxygenation (+2 O)	3.42	221.1281	−1.5
M4	C12H16N2O	Oxygenation (+O)	4.26	205.1329	−3.0
DMT	C12H16N2	–	9.37	189.1384	−1.2

Figure 3. Fragmentation patterns of DMT and the identified metabolites at a collision energy of 10 eV.

Figure 4. Proposed metabolic pathway of DMT via CYP2D6.