The syntheses, characterization and in vitro metabolism of nitracaine, methoxypiperamide and mephtetramine

Drug Test Anal. 2014 Jul-Aug;6(7-8):668-75. doi: 10.1002/dta.1616. Epub 2014 Jan 29.

Abstract

Three legal highs; nitracaine (3-(diethylamino)-2,2-dimethylpropyl 4-nitrobenzoate), methoxypiperamide (MEOP, (4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone) and mephtetramine (MTTA, 2-((methylamino)methyl)-3,4-dihydronaphthalen-1(2H)-one) appeared in 2013 as new psychoactive substances (NPS) on Internet websites selling 'research chemicals'. These compounds were synthesized and analyzed via our synthesize, analyze, and metabolize (SAM) protocol. Nitracaine was synthesized by the transesterification of methyl 4-nitrobenzoate with 3-(diethylamino)-2,2-dimethylpropan-1-ol. Methoxypiperamide was synthesized by the reaction of 4-methoxybenzoyl chloride with 1-methylpiperazine, and mephtetramine through the Mannich reaction of 1-tetralone with paraformaldehyde and methylamine hydrochloride. Each compound was characterized by nuclear magnetic resonance (NMR), gas chromatography with electron impact mass spectrometry (GC-EIMS), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and high resolution electrospray ionization mass spectrometry (HR-ESI-MS). A sample of nitracaine was also test-purchased from an Internet vendor and its structure confirmed by GC-EIMS and LC-ESI-MS. Finally, the in vitro metabolism of the nitracaine, mephtetramine, and methoxypiperamide was investigated, using a human microsomal liver extract, in order to tentatively identify potential metabolites that may be encountered in the analysis of biological samples in clinical or toxicology labs. The use of our SAM protocol highlights the ability of academic research labs to quickly respond to and disseminate information about emerging NPS.

Keywords: NPS; characterization; mephtetramine; metabolite; methoxypiperamide; new psychoactive substance; nitracaine; synthesis.

MeSH terms

  • Chromatography, Liquid
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Illicit Drugs / analysis*
  • Illicit Drugs / chemical synthesis
  • Illicit Drugs / metabolism
  • Magnetic Resonance Spectroscopy
  • Microsomes, Liver / metabolism
  • Naphthalenes / analysis*
  • Naphthalenes / chemical synthesis
  • Naphthalenes / metabolism
  • Nitrobenzoates / analysis*
  • Nitrobenzoates / chemical synthesis
  • Nitrobenzoates / metabolism
  • Piperazines / analysis*
  • Piperazines / chemical synthesis
  • Piperazines / metabolism
  • Psychotropic Drugs / analysis*
  • Psychotropic Drugs / chemical synthesis
  • Psychotropic Drugs / metabolism
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • 3,4 dihydronaphthalen-1(2H)-one
  • Illicit Drugs
  • Naphthalenes
  • Nitrobenzoates
  • Piperazines
  • Psychotropic Drugs