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

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 C 6 ]‐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 C 6 ]‐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 C 6 ]‐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. Copyright © 2014 John Wiley & Sons, Ltd.