Forensic science international
March 10, 2009
Jochen Beyer, Olaf H Drummer, Hans H Maurer
118 citations
Fatal plant poisonings are rare, though many plants contain dangerous alkaloids. Poisonings fall into three categories: accidental ingestions (often in children or from plant-mushroom mix-ups in adults), intentional ingestions (homicides and suicides), and abuse of plants for hallucinogenic effects. This review describes toxic alkaloids such as aconitine, atropine, coniine, colchicine, cytisine, dimethyltryptamine, harmine, harmaline, ibogaine, kawain, mescaline, scopolamine, and taxine, which are involved in fatal and non-fatal poisonings. It summarizes intoxication symptoms and reviews methods for detecting these substances in biological fluids.
Current drug metabolism
June 1, 2010
Markus R Meyer, Hans H Maurer
112 citations
This review updates a 2005 paper on how the body metabolizes new designer drugs that have appeared on the black market. It covers 2C compounds (phenethylamines like 2C-B, 2C-I, 2C-D, 2C-E, 2C-T-2, and 2C-T-7), beta-keto drugs (butylone, ethylone, methylone, mephedrone), pyrrolidinophenones (MPBP and PVP), phencyclidine-derived drugs (PCPr, PCEEA, PCMPA, PCMEA), tryptamines (5-MeO-DIPT), and fentanyl analogs (alpha-MF and 3-MF). The review focuses on studies that identified human or animal metabolites formed in vivo or in vitro and the roles of cytochrome P450 and monoamine oxidase enzymes in their metabolism.
Journal of mass spectrometry : JMS
June 1, 2005
Vilma Habrdova, Frank T Peters, Denis S Theobald et al.
61 citations
A new method using gas chromatography/mass spectrometry was developed to screen and quantify seven 2C-series designer drugs (2C-D, 2C-E, 2C-P, 2C-B, 2C-I, 2C-T-2, 2C-T-7) and mescaline in human blood plasma. The method involves solid-phase extraction and derivatization, and was validated per international guidelines. Validation for 2C-T-2 and 2C-T-7 was unacceptable; for the other analytes, the method was linear from 5 to 500 microg/L with accuracy and precision within acceptable limits. This addresses the scarcity of data on analyzing these substances in blood or plasma.
Biochemical pharmacology
January 15, 2007
Denis S Theobald, Hans H Maurer
59 citations
For several phenethylamine-type designer drugs (2C-series), the main metabolic step is deamination to an aldehyde. Using human enzymes expressed in cell culture, monoamine oxidase A and B (MAO-A and MAO-B) were the primary catalysts of this reaction for all compounds tested. For four of the six drugs (2C-D, 2C-E, 2C-T-2, and 2C-T-7), the cytochrome P450 enzyme CYP2D6 contributed to a very small extent. Because MAO enzymes are the major route of metabolism, these designer drugs are likely to be susceptible to drug-drug interactions with MAO inhibitors.
Journal of mass spectrometry : JMS
July 1, 2006
Denis S Theobald, Michael Pütz, Erhard Schneider et al.
51 citations
The designer drug 2C-I is metabolized in rats through O-demethylation, deamination, oxidation, and reduction pathways, producing multiple metabolites that are partly excreted in conjugated form. A systematic toxicological analysis using gas chromatography/mass spectrometry after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation reliably detected a dose of 2C-I in rat urine equivalent to a common human drug user's dose. Assuming similar metabolism in humans, this detection method should be suitable for proving 2C-I intake in human urine.
Analytical and bioanalytical chemistry
October 1, 2015
Julian A Michely, Andreas G Helfer, Simon D Brandt et al.
49 citations
N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamines with psychoactive effects. In rats, after high-dose administration, their metabolism involves aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations; 5-MeO-DALT also undergoes O-demethylation, followed by extensive glucuronidation or sulfation. The main cytochrome P450 enzymes for DALT are CYP2C19, CYP2D6, and CYP3A4; for 5-MeO-DALT, CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detecting low-dose consumption in rat urine, LC-MS(n) and LC-HR-MS-MS are suitable; the most abundant markers are a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC-MS can screen DALT only via its main metabolites.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
October 2, 2006
Denis S Theobald, Hans H Maurer
42 citations
The designer drug 2C-E is metabolized in rats through several pathways: O-demethylation, N-acetylation, hydroxylation of the ethyl side chain, oxidation to ketones or acids, and deamination followed by reduction to alcohols. Most metabolites are excreted in conjugated form. A systematic toxicological analysis using full-scan GC-MS detected intake of a dose corresponding to a common drug users' dose in rat urine. Assuming similar metabolism in humans, the procedure should be suitable for proving 2C-E intake in human urine.
Analytical and bioanalytical chemistry
January 1, 2014
Markus R Meyer, Achim Caspar, Simon D Brandt et al.
39 citations
A new laboratory method using liquid chromatography and linear ion trap mass spectrometry can detect 37 synthetic tryptamines plus five β-carbolines, ibogaine, and yohimbine in human urine and plasma. The method is selective for all tested substances, with detection limits in urine between 10 and 100 ng/mL and in plasma between 1 and 100 ng/mL. Validated quantification in plasma was achieved for 33 of the 44 analytes. This addresses the previous scarcity of analytical data on detecting these emerging designer drugs in human biosamples.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
February 1, 2007
Denis S Theobald, Giselher Fritschi, Hans H Maurer
37 citations
The designer drug 2C-B is extensively metabolized and excreted mainly as metabolites in urine. In rats, a systematic toxicological analysis using full-scan GC-MS detected the O-demethyl deaminohydroxy metabolite and two isomers of the O-demethyl metabolite after a common drug abuser's dose. The authors suggest that, assuming similar metabolism in humans, this procedure should be suitable for proving 2C-B intake in human urine.
Drug testing and analysis
January 1, 2018
Achim T Caspar, Jonas B Gaab, Julian A Michely et al.
33 citations
Three new psychoactive tryptamines—5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT—are mainly broken down in the body through O-demethylation, hydroxylation, and N-dealkylation, followed by glucuronidation or sulfation. In rats given 20 mg/kg doses, 5-MeO-2-Me-DALT produced 24 phase I and 12 phase II metabolites, 5-MeO-2-Me-ALCHT produced 24 phase I and 14 phase II metabolites, and 5-MeO-2-Me-DIPT produced 20 phase I and 11 phase II metabolites. Human liver enzyme incubations suggest the same major metabolic pathways occur in humans. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 catalyze hydroxylation; CYP2C19 and CYP2D6 catalyze O-demethylation; and CYP2C19, CYP2D6, and CYP3A4 catalyze N-dealkylation. Liquid chromatography-based urine screening detected intake of all three compounds after low doses (0.1–1 mg/kg), whereas gas chromatography-based screening did not.
Drug testing and analysis
February 1, 2019
Lea Wagmann, Simon D Brandt, Alexander Stratford et al.
26 citations
Thirteen of 17 phenethylamine-derived designer drugs (12 from the 2C-series and five FLY analogs) inhibited monoamine oxidase A (MAO-A), and 11 inhibited monoamine oxidase B (MAO-B) in an in vitro assay using heterologously expressed enzymes and hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry. For the seven drugs where MAO-A IC50 values were determined, values ranged from 10 to 125 μM; for the nine drugs with MAO-B IC50 values, the range was 1.7 to 180 μM. Because clinical information on most test drugs is lacking, a pharmacological contribution of MAO inhibition cannot be excluded, and further studies are warranted.
Analytical and bioanalytical chemistry
February 1, 2017
Julian A Michely, Simon D Brandt, Markus R Meyer et al.
23 citations
Derivatives of N,N-diallyltryptamine (DALT) are new psychoactive substances. Their metabolism and detectability were studied in rat urine and human liver microsomes using liquid chromatography-high resolution-tandem mass spectrometry. Main metabolic pathways include aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations; carboxylation was detected for 7-Me-DALT and O-demethylenation for 5,6-MD-DALT. Phase I metabolites were extensively glucuronidated or sulfated, catalyzed by several CYP isoenzymes. GC-MS could not reliably monitor consumption, but LC-MSn and LC-HR-MS/MS approaches were suitable, especially for detecting 5-F-DALT and 7-Me-DALT at low doses. The most abundant targets for each compound are specified.
Talanta
October 1, 2018
Achim T Caspar, Markus R Meyer, Folker Westphal et al.
17 citations
Two new hallucinogens, 3,4-DMA-NBOMe and 4-MMA-NBOMe, are extensively metabolized in rats and human liver preparations. Using nano liquid chromatography with high-resolution mass spectrometry, 38 metabolites of 3,4-DMA-NBOMe and 33 metabolites of 4-MMA-NBOMe were identified. The main metabolic pathways are O-demethylation and glucuronic acid conjugation for 3,4-DMA-NBOMe, and oxidation of the tolyl group to carboxylic acid for 4-MMA-NBOMe. The nanoLC approach performed comparably to conventional UHPLC. Standard urine screening methods could detect an estimated low user dose only through metabolites. Suggested screening targets include O-demethyl- and O,O-bis-demethyl-3,4-DMA-NBOMe and their glucuronides, and carboxy-4-MMA-NBOMe and its glucuronide and N-demethyl-carboxy-4-MMA-NBOMe.
Drug testing and analysis
January 1, 2017
Simon D Brandt, Pierce V Kavanagh, Geraldine Dowling et al.
16 citations
Many N,N-dialkylated tryptamines have psychoactive properties in humans, and the number of derivatives has grown across research areas. Some are used in medicinal products, others as recreational drugs, and sometimes these uses overlap. 5-Methoxy-N,N-diallyltryptamine (5-MeO-DALT) recently emerged as a new psychoactive substance, while 4-acetoxy-DALT and unsubstituted DALT have been detected only recently. This report describes the analytical characterization of 17 N,N-diallyltryptamines (DALTs), including 15 prepared via microwave-accelerated synthesis. The compounds were characterized using NMR, GC-MS, mass spectrometry, photodiode array detection, and GC solid-state infrared analysis. The resulting spectral data are provided to help researchers identify newly emerging substances and explore clinical and non-clinical uses.
Analytical and bioanalytical chemistry
January 1, 2015
Carina S D Wink, Markus R Meyer, Tina Braun et al.
13 citations
2C-P is a hallucinogenic designer drug from the phenethylamine class. This work identified its phase I and II metabolites and tested detectability in urine. Proposed metabolic pathways include N-acetylation, deamination with reduction to alcohol or oxidation to carbonic acid, mono- and bis-hydroxylation, mono- and bis-O-demethylation followed by glucuronidation or sulfation, and combinations. A common user's dose of 2C-P was reliably detectable in urine using standard GC-MS and LC-MS(n) screening methods, supporting its identification in clinical and forensic cases.