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.
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.
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany, markus.meyer@uks.eu.
Markus R
MR
Meyer
Carina
C
Lindauer
Jessica
J
Welter
Hans H
HH
Maurer
D062365:Aminobenzoates / Q000378:metabolism* / Q000652:urine*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003042:Cocaine / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D011412:Propanolamines / Q000378:metabolism* / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D052616:Solid Phase Extraction; D015813:Substance Abuse Detection / Q000295:instrumentation / Q000379:methods*
D062365:Aminobenzoates; D011412:Propanolamines; D003042:Cocaine; C066888:dimethocaine