Quantitation of R-(-)- and S-(+)-amphetamine in hair and blood by gas chromatography-mass spectrometry:: An application to compliance monitoring in adult-attention deficit hyperactivity disorder treatment

Amphetamine has been used in Attention Deficit Hyperactivity Disorder (ADHD), narcolepsy, and as an appetite suppressant either as the racemate or in different proportions of its enantiomers. In Linköping, Sweden, the Department for Drug Dependence has successfully treated drug abusers also diagnosed with Adult ADHD with Metamina® [S-(+)-amphetamine]. Because of the high risk of relapse into drug abuse, a strategy involving the analysis of amphetamine enantiomers in blood and hair was investigated for the assessment of compliance as well as abstinence from street amphetamine. Four patients were included: one patient was treated with racemic amphetamine, and three with Metamina. Blood and hair samples were obtained as a part of the treatment. A basic extraction of the analytes into iso-octane was used. Hair was dissolved in sodium hydroxide before extraction. Chiral derivatization was performed by reaction with S- (-) -N-(trifluoroacetyl)prolyl chloride. Quantitation of R-(-)- and S-(+)-amphetamine was performed by gas chromatography-mass spectrometry in selected ion monitoring. Both blood and hair sample results showed good compliance for patients 1 and 2. Patient 3 and 4 showed different percentages of S-(+)-amphetamine in hair together with varying total concentrations, suggesting intake of additional racemic illicit amphetamine. During treatment, these patients also showed other signs of noncompliance, and one was temporarily withdrawn from treatment. We conclude that the method is suitable to detect therapeutic concentrations of R-(-)- and S-(+)-amphetamine in both blood and hair and that hair reveals noncompliance not shown by concentrations or enantiomer ratios in blood.