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

Anal Bioanal Chem. 2014 Mar;406(7):1845-54. doi: 10.1007/s00216-013-7539-0. Epub 2014 Jan 22.


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.

MeSH terms

  • Aminobenzoates / metabolism*
  • Aminobenzoates / urine*
  • Animals
  • Chromatography, Liquid / methods*
  • Cocaine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Male
  • Mass Spectrometry / methods*
  • Metabolic Detoxication, Phase I
  • Metabolic Detoxication, Phase II
  • Propanolamines / metabolism*
  • Propanolamines / urine*
  • Rats
  • Rats, Wistar
  • Solid Phase Extraction
  • Substance Abuse Detection / instrumentation
  • Substance Abuse Detection / methods*


  • Aminobenzoates
  • Propanolamines
  • Cocaine
  • dimethocaine