title: Synthesis of [13C6]-labelled phenethylamine derivatives for drug quantification in biological samples.
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.
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491, Trondheim, Norway; Chiron AS, Stiklestadveien 1, 7041, Trondheim, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Karlsen
authors.forename: HuiLing
authors.initials: H
authors.lastname: Liu
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Jon Eigill
authors.initials: JE
authors.lastname: Johansen
authors.forename: Bård Helge
authors.initials: BH
authors.lastname: Hoff
mesh_terms: D002247:Carbon Isotopes / Q000032:analysis* / Q000737:chemistry*; D015195:Drug Design; D007553:Isotope Labeling; D013058:Mass Spectrometry / Q000379:methods*; D010627:Phenethylamines / Q000032:analysis* / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D002247:Carbon Isotopes; D010627:Phenethylamines; D019275:Radiopharmaceuticals; C029261:phenethylamine
keywords: 3,4-methylenedioxymethamphetamine; 4-methoxymethamphetamine; Stille coupling; [13C6]-labelled standards; amphetamine; methamphetamine