Chiral analysis of amphetamines in hair by liquid chromatography–tandem mass spectrometry: compliance‐monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low‐dose application

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EarlyView Article

  • Published: Jul 5, 2017
  • Author: Tina M. Binz, Elena Williner, Petra Strajhar, Patrick C. Dolder, Matthias E. Liechti, Markus R. Baumgartner, Thomas Kraemer, Andrea E. Steuer
  • Journal: Drug Testing and Analysis

Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)‐AMP as active compound or (S)‐AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)‐AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the chiral separation and quantitation of (S)‐ and (R)‐AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N‐(2,4‐dinitro‐5‐fluorophenyl)‐L(S)‐valinamide L(S)‐(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high‐pressure liquid‐chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)‐AMP in eight cases; one subject showed both enantiomers indicating a (side‐) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)‐AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug‐facilitated crime (DFC). The method now enables the retrospective compliance‐monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)‐amphetamine and abuse of illicit street amphetamine.

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