Dimethocaine, a synthetic cocaine analogue: studies on its in-vivo metabolism and its detectability in urine by means of a rat model and liquid chromatography–linear ion-trap (high-resolution) mass spectrometry
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Dimethocaine (DMC, larocaine), a synthetic derivative of cocaine, is a widely distributed “legal high” consumed as a “new psychoactive substance” (NPS) without any safety testing, for example studies of metabolism. Therefore, the purpose of this work was to study its in-vivo and in-vitro metabolism by use of liquid chromatography–(high resolution) mass spectrometry (LC–HRMS n ). DMC was administered to male Wistar rats (20 mg kg−1) and their urine was extracted either by solid-phase extraction after enzymatic cleavage of conjugates or by use of protein precipitation (PP). The metabolites were separated and identified by LC–HRMS n . The main phase I reactions were ester hydrolysis, deethylation, hydroxylation of the aromatic system, and a combination of these. The main phase II reaction was N-acetylation of the p-aminobenzoic acid part of the unchanged parent compound and of several phase I metabolites. The metabolites identified were then used for identification of DMC in rat urine after application of a common user’s dose. By use of GC–MS and LC–MS n standard urine-screening approaches (SUSAs), DMC and its metabolites could be detected in the urine samples.
KeywordsDesigner drug DMC Cocaine Metabolism Urine screening GC–MS LC–MSn LC–HRMSn
The authors would like to thank Carina S.D. Wink, Julia Dinger, Golo M.J. Meyer, Carsten Schröder, Armin Weber, and Gabriele Ulrich for their support.
- 1.Hoffmann–La Roche F (1948) Loracain Roche. In: Hoffmann–La Roche, F. Compendium Roche. Hoffmann–La Roche, Basel, 79–81Google Scholar
- 4.Graham JH III, Maher JR, Robinson SE (1995) The effect of cocaine and other local anesthetics on central dopaminergic neurotransmission. J Pharmacol Exp Ther 274:707–717Google Scholar
- 6.European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2013) Synthetic cocaine derivatives. http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cocaine-derivatives
- 7.Maurer HH, Pfleger K, Weber AA (2011) Mass Spectral Library of Drugs, Poisons, Pesticides, Pollutants and their Metabolites. Wiley–VCH, WeinheimGoogle Scholar
- 10.Meyer MR, Vollmar C, Schwaninger AE, Maurer HH (2012) New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC–MS and LC–high-resolution MS and their detectability in urine. J Mass Spectrom 47:253–262CrossRefGoogle Scholar
- 11.Maurer HH, Pfleger K, Weber AA (2011) Mass Spectral and GC Data of Drugs, Poisons, Pesticides, Pollutants and their Metabolites. Wiley–VCH, WeinheimGoogle Scholar
- 17.Yuan J, Yin J, Wang E (2007) Characterization of procaine metabolism as probe for the butyrylcholinesterase enzyme investigation by simultaneous determination of procaine and its metabolite using capillary electrophoresis with electrochemiluminescence detection. J Chromatogr A 1154:368–372CrossRefGoogle Scholar