Therapeutic Drug Monitoring
April 1, 2002
Thomas Kræmer, Hans H. Maurer
232 citations
Amphetamines and related designer drugs are metabolized primarily by cytochrome P450 enzymes, with many N-alkylated derivatives acting as prodrugs that convert to active amphetamine or methamphetamine. The review covers MDA, MDMA, MDE, BDB, MBDB, and several N-alkylated amphetamines including methamphetamine, benzphetamine, and selegiline. It summarizes findings from English-language publications between 1995 and 2000 on metabolite identification, cytochrome P450-dependent metabolism, and pharmacokinetic or toxicokinetic data. The implications of these toxicokinetic pathways for forensic toxicology and interpretation in legal cases are discussed.
Journal of Mass Spectrometry
June 1, 2003
Frank T. Peters, Simone Schaëfer, Roland F. Staack et al.
171 citations
A method was developed to screen for and simultaneously quantify classical stimulants (amphetamine, methamphetamine, ethylamphetamine, MDA, MDMA, MDEA, BDB, MBDB) and newer designer drugs (4-methylthioamphetamine, p-methoxyamphetamine, p-methoxymethamphetamine, and several piperazine derivatives) along with two metabolites in human blood plasma. The technique uses gas chromatography/mass spectrometry with selected-ion monitoring after solid-phase extraction and derivatization. The method was linear from 5 to 1000 µg/L for all analytes, with a limit of quantification of 5 µg/L. Accuracy and precision met required limits except for MDBP. The assay was validated and applicable for confirming immunoassay results positive for amphetamines or ecstasy-type designer drugs.
Therapeutic Drug Monitoring
March 19, 2004
Hans H. Maurer, Thomas Kræmer, Dietmar Springer et al.
147 citations
Designer drugs such as MDMA, MDEA, MDA, and various piperazine and pyrrolidinophenone compounds, often used as rave drugs, produce euphoria, energy, and sociability. Despite their reputation as safe, studies in rats and primates along with human epidemiological investigations indicate potential risks, including serotonin syndrome, liver toxicity, neurotoxicity, and psychological problems. Metabolites may contribute to some toxic effects, so understanding metabolism is crucial for risk assessment. The enzyme CYP2D6, which is polymorphically expressed, catalyzes the major metabolic steps of piperazine- and pyrrolidinophenone-derived designer drugs, though it remains unclear whether this genetic polymorphism is clinically relevant.
Clinical Pharmacokinetics
February 14, 2017
Patrick C. Dolder, Yasmin Schmid, Andrea E. Steuer et al.
134 citations
After oral administration, lysergic acid diethylamide (LSD) reaches peak plasma concentrations of 1.3 ng/mL (100 µg dose) and 3.1 ng/mL (200 µg dose) within about 1.5 hours, with a plasma half-life of 2.6 hours. Subjective effects last 8 to 12 hours depending on dose, and peak effects occur around 2.5 to 2.8 hours after ingestion. A close relationship exists between LSD concentration and subjective response within individuals, but no correlation was found between plasma levels and effects across different people at peak concentration. The effects are related to changing plasma concentrations over time, without evidence of acute tolerance.
Journal of Analytical Toxicology
November 1, 2003
Frank T. Peters, Nele Samyn, Martin Wahl et al.
65 citations
The pharmacological effects of amphetamine, methamphetamine, MDA, MDMA, and MDEA depend on their mirror-image molecular forms (enantiomers), which differ in how they act in the body. Analysis of plasma from clinical toxicology cases and from drivers suspected of drug impairment showed that concentrations of most enantiomers were lower in routine screening samples than in intoxication or driving-under-the-influence cases. Drivers under the influence had higher levels of both amphetamine enantiomers than intoxicated patients. Differences in the ratio of R to S enantiomers for several drugs between groups suggest these ratios can help distinguish recent from past use. In one MDMA poisoning, the R form cleared more slowly (half-life 6.0 hours) than the S form (4.1 hours), and the ratio of R to S rose over time.
Clinical Chemistry
August 11, 2005
Frank T. Peters, Nele Samyn, C. T. J. Lamers et al.
49 citations
An assay was developed to measure the enantiomers of the designer drugs MDA, MDMA, and MDEA in small plasma volumes (0.2 mL or less). After extraction and derivatization, the enantiomers were separated by gas chromatography and detected by mass spectrometry within 17 minutes. The method was linear for MDA at 1–50 μg/L and for MDMA and MDEA at 5–250 μg/L per enantiomer, with extraction yields of 82.1%–95.3%. Applied to samples from a controlled study after a single 75 mg dose of racemic MDMA, the assay showed that R-(−)-MDMA concentrations significantly exceeded those of S-(+)-MDMA, with ratios always above 1.0 and increasing over time. S-(+)-MDA concentrations exceeded those of R-(−)-MDA, with ratios also increasing but remaining below 1.0.
Drug Testing and Analysis
July 16, 2016
Andrea E. Steuer, Michael Poetzsch, Lorena Stock et al.
41 citations
A new microflow liquid chromatography tandem mass spectrometry method was developed to quantify LSD and its metabolites in human plasma, enabling detection limits of 0.01 ng/mL and separation within three minutes. In a controlled pharmacokinetic study, elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded that of LSD (median 4.2 h). However, screening for these metabolites to extend detection windows in plasma is not constructive because their concentrations are very low.
Clinical Chemistry
March 2, 2007
Frank T. Peters, Nele Samyn, Thomas Kræmer et al.
36 citations
A gas chromatography–mass spectrometry method using negative-ion chemical ionization was developed to separately measure the left- and right-handed forms (enantiomers) of amphetamine, methamphetamine, MDA, MDMA, and MDEA in oral fluid. After adding a buffer and a derivatizing agent, the enantiomers were extracted and analyzed. The method was linear from 5–250 μg/L per enantiomer for MDA and from 25–1250 μg/L per enantiomer for the other drugs. Recoveries and precision were acceptable except for MDEA. When applied to samples from a controlled MDMA study and real driving-under-the-influence cases, the oral fluid concentrations and enantiomer ratios did not reliably predict plasma levels.