[Harmonized measurement and reporting of chiral amphetamine in the follow-up of ADHD treatment]

Abstract

Amphetamine is an illicit central nervous system stimulant that is also used for the treatment of attention-decific/hyperacticity disorder (ADHD). Amphetamine exits as two enantiomers, dex(tro)amphetamine (D-amphetamine; also called S-amphetamine) and levoamphetamine (L-amphetamine; or R-amphetamine), of which mainly the former is used as medication for ADHD, whereas illicit street amphetamine is a racemic mixture. To monitor patient compliance with treatment and detect (side) intake of racemic amphetamine, chiral analysis in samples of urine, oral fluid, or blood is used and has traditionally involved reporting of the L/D ratio. Today in Sweden, however, only ADHD medications based on D-amphetamine (lisdexamphetamine lysate and dexamphetamine sulfate) are approved, so no L-amphetamine should be found in the samples provided treatment compliance. It is therefore advisable to instead report the total amphetamine concentration and the relative amount of L-amphetamine. A proposed L-amphetamine cutoff for compliance with ADHD medication is less than 1%, or as low as possible in samples with low amphetamine concentration, as there may be traces of L-amphetamine in the approved pharmaceutical products. Since (supervised) urine sampling is sometimes considered sensitive to ADHD patients without any underlying drug problem, using oral fluid testing is a less invasive alternative and would facilitate sampling for both patients and healthcare professionals. However, an analytical disadvantage is that the amphetamine concentration is generally lower in oral fluid than in urine.