Synthesis of [13C6]-labelled phenethylamine derivatives for drug quantification in biological samples

J Labelled Comp Radiopharm. 2014 May 15;57(5):378-87. doi: 10.1002/jlcr.3193. Epub 2014 Mar 14.

Abstract

The availability of high-quality (13)C-labelled internal standards will improve accurate quantification of narcotics and drugs in biological samples. Thus, the synthesis of 10 [(13)C6]-labelled phenethylamine derivatives, namely amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, 4-methoxyamphetamine, 4-methoxymethamphetamine, 3,5-dimethoxyphenethylamine 4-bromo-2,5-dimethoxyphenethylamine and 2,5-dimethoxy-4-iodophenethylamine, have been undertaken. [(13)C6]-Phenol proved to be an excellent starting material for making (13)C-labelled narcotic substances in the phenethylamine class, and a developed Stille-type coupling enabled an efficient synthesis of the 3,4-methylenedioxy and 4-methoxy derivatives. The pros and cons of alternative routes and transformations are also discussed. The [(13)C6]-labelled compounds are intended for use as internal standards in forensic analysis, health sciences and metabolomics studies by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.

Keywords: 3,4-methylenedioxymethamphetamine; 4-methoxymethamphetamine; Stille coupling; [13C6]-labelled standards; amphetamine; methamphetamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Isotopes / analysis*
  • Carbon Isotopes / chemistry*
  • Drug Design
  • Isotope Labeling
  • Mass Spectrometry / methods*
  • Phenethylamines / analysis*
  • Phenethylamines / chemistry*
  • Radiopharmaceuticals / chemical synthesis*
  • Substance Abuse Detection / methods*

Substances

  • Carbon Isotopes
  • Phenethylamines
  • Radiopharmaceuticals
  • phenethylamine