A qualitative/quantitative approach for the detection of 37 tryptamine-derived designer drugs, 5 β-carbolines, ibogaine, and yohimbine in human urine and plasma using standard urine screening and multi-analyte approaches

Abstract

The first synthetic tryptamines have entered the designer drug market in the late 1990s and were distributed as psychedelic recreational drugs. In the meantime, several analogs have been brought onto the market indicating a growing interest in this drug class. So far, only scarce analytical data were available on the detectability of tryptamines in human biosamples. Therefore, the aim of the presented study was the development and full validation of a method for their detection in human urine and plasma and their quantification in human plasma. The liquid chromatography-linear ion trap mass spectrometry method presented covered 37 tryptamines as well as five β-carbolines, ibogaine, and yohimbine. Compounds were analyzed after protein precipitation of urine or fast liquid-liquid extraction of plasma using an LXQ linear ion trap coupled to an Accela ultra ultra high-performance liquid chromatography system. Data mining was performed via information-dependent acquisition or targeted product ion scan mode with positive electrospray ionization. The assay was selective for all tested substances with limits of detection in urine between 10 and 100 ng/mL and in plasma between 1 and 100 ng/mL. A validated quantification in plasma according to international recommendation could be demonstrated for 33 out of 44 analytes.

Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC–MS, LC–MS n , and LC–HR–MS–MS

“…(2) and N-oxidation could also be observed. The following combinations could be proposed from these observations: aromatic and aliphatic hydroxylation in section 2 (11), N-oxidation with aliphatic hydroxylation in section 3 (12), and N-dealkylation with aromatic hydroxylation (3,4). Glucuronidation and sulfation could be observed for both isomers of the aryl hydroxylated metabolites with (3, 4) and without (7,8) N-dealkylation.…”

“…They interact with the serotonergic system, which includes activation of the 5-HT 1A and 5-HT 2A receptor subtypes [3] and increase of serotonin release [4][5][6][7][8] nmol/mL of human cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 (2 nmol/mL), CYP3A4, or CYP3A5 (2 nmol/mL), and pooled human liver microsomes (pHLM, 20 mg microsomal protein/mL, 400 pmol total CYP/mg protein) were obtained from BD Biosciences (Heidelberg, Germany). After delivery, the microsomes were thawed at 37 °C, divided into aliquots, snap-frozen in liquid nitrogen, and stored at -80 °C until use.…”

Contribution of human esterases to the metabolism of selected drugs of abuse

“…The MS conditions were as previously described (Meyer et al, 2014;Wissenbach et al, 2011). The instrument was operated in positive electrospray ionization mode; sheath gas, nitrogen at flow rate of 34 arbitrary units (AU); auxiliary gas, nitrogen at flow rate of 11 AU; vaporizer temperature, 250 C; source voltage, 3.00 kV; ion transfer capillary temperature, 300 C; capillary voltage, 31 V; and tube lens voltage, 80 V. Automatic gain control was set to 15,000 ions for full scan and 5000 ions for MS n .…”

Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS

“…As Cozzi and Daley [13] described pharmacological potency for 5-substitued DALTs and Wagmann et al the inhibition of the monoamine oxidase A (publication in preparation) it can be assumed that such compounds will appear once on the drugs of abuse market. So far, only spectroscopic data [14] and an LC-MS n approach for qualitative and quantitative of tryptamines in plasma and urine covering only the parent drugs [15] were published.…”