O45. Metabolism of the new designer drug mephedrone
and toxicological detection of the beta keto designer drugs
mephedrone, butylone and methylone in urine
M.R. Meyer, F.T. Peters, H.H. Maurer
Department of Experimental and Clinical Toxicology, Saarland University,
D-66421 Homburg (Saar), Germany
Introduction: Beta keto (bk) designer drugs are a new class of drugs of
abuse. In contrast to mephedrone (2-methylamino-1-p-tolylpropane-1-one),
the metabolism of butylone (2-methylamino-1-(3,4-methylenedioxyphenyl)
butan-1-one, bk-MBDB) and methylone (3,4-methylenedioxymethcathinone,
bk-MDMA) has already been investigated. So far, these designer drugs have
not yet been included in our systematic toxicological analysis (STA).
Aim: The first aim of the presented work was to study the metabolism of
mephedrone and to incorporate all of the above-mentioned bk-designer drugs
into our STA. The second aim was to check for suitability of our rat model
by comparing incurred rat urine samples with human urine samples from
mephedrone and butylone users.
Methods: For the metabolism study, urine samples from male Wistar rats
(20 mg/kg BW) were extracted (liquid-liquid or Isolute Confirm HCX
cartridges) after enzymatic cleavage of conjugates. After extraction and
acetylation, the metabolites were separated and identified by GC–MS in
the electron ionisation and in the positive chemical ionisation mode. For
toxicological detection, a common users dose corresponding to 1 mg/kg
BW were administered to rats and urine was collected over a 24 h period.
Human urine submitted to our laboratory for toxicological analysis was
collected approximately 6 hours after intake of an unknown amount of
butylone and mephedrone. The rat and human urine samples were analyzed
using our STA based on an acid hydrolysis followed by liquid-liquid
extraction, acetylation and analysis via full-scan GC-MS. Finally, the
results from the metabolism and screening studies in rats were compared
to those obtained from the patients’ urine to verify the suitability of the
used rat model.
Results: Analysis of the rat and human samples revealed the following
main metabolic steps for mephedrone: N-demethylation to the primary
amine, reduction of the keto moiety to the respective alcohol and oxidation
of the tolyl moiety to the corresponding alcohols and carboxylic acids. The
metabolites of butylone and mephedrone detected in rat urine could also be
found in human urine samples. Using our STA, the parent compounds and
N-demethyl metabolites could be detected in rat urine after a common user’s
dose as well as in the patients’ urine samples in the case of mephedrone and
butylone.
Conclusion: Besides the elucidation of the metabolism of the new designer
drug mephedrone, we were able to show, that our STA was suitable to proof
S1-23
Ann Toxicol Anal. 2009; 21(S1) Abstracts
an intake of at least butylone and/or mephedrone in human urine. These
examples showed again that the used rat model was suitable to predict the
qualitative metabolism and detectability of drugs in human urine.
Keywords: designer drugs, butylone, mephedrone, methylone, metabolism