M FANZUN¹, C SEGER¹, M RISCH<sup>1

1</sup>Risch Laboratory Group, Schaan, Principality of Liechtenstein

Screening efforts for drug abuse testing usually rely on immunological methods applied to urines samples. Antibodies raised for such assays are designed to have broad structural cross-section allowing coverage of whole analyte classes such as “benzodiazepins”, “amphetamins” or “opiates”. Beside the obvious advantage of this approach in clinical settings aiming for fast orientating results in emergency situations, this cross-reactivity can be interpreted as major drawback of this strategy, since confirmative testing by specific methods as LC-MS is mandatory. In this context we report on an isolated positive amphetamine result in immunological urinary drug testing. Investigation of the medical history of the case revealed, that the patient was under therapy with lisdexamfetamine, a CNS stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD). This compound is a classical prodrug; upon enzymatic cleavage of a peptide bond dextroamphetamine is released in the blood. On the basis of MS2 / MS3 experiments using LC-IT-MS technology it was possible to unequivocally identify the drug in urine and serum specimen. Since also the prodrug – which has a short half-life time of less than one hour – was found and confirmed in both materials, an amphetamine drug abuse was made highly unlikely. This prodrug / drug pair means an additional analytical challenge in amphetamine screening efforts and – as already known from benzodiazepine or TCA measurements – do make the distinction between TDM and toxicology to become more blurred than ever.