Abstract
Dexamphetamine, lisdexamphetamine, and methylphenidate are central stimulant drugs widely used to treat attention-deficit/hyperactivity disorder (ADHD), but poor adherence may lead to treatment failure, and the drugs are also subject to misuse and diversion. Drug analysis in oral fluid may thus be useful for monitoring adherence and misuse. We measured drug concentrations in oral fluid and urine after controlled dosing to investigate detection windows and evaluate the chosen cutoffs. Healthy volunteers ingested single oral doses of 10 mg dexamphetamine (n = 11), 30 mg lisdexamphetamine (n = 11), or 20 mg methylphenidate (n = 10), after which they collected parallel oral fluid and urine samples every 8 h for 4-6 days. Amphetamine (analytical cutoff, oral fluid: 1.5 ng/mL; urine: 50 ng/mL), methylphenidate (oral fluid: 0.06 ng/mL), and ritalinic acid (urine: 500 ng/mL) were analyzed using fully validated chromatographic methods. The median time from ingestion to the last detection in oral fluid was 67 ± 4.9 h (lisdexamphetamine) and 69 ± 8.8 h (dexamphetamine) for amphetamine and 36 ± 2.5 h for methylphenidate. This was comparable to urine (77 ± 5.1 h for lisdexamphetamine, 78 ± 4.5 h for dexamphetamine, and 41 ± 2.4 h for ritalinic acid). The interindividual variability in detection times was large, probably in part due to pH-dependent disposition. Using a logistic regression approach, we found similar detection rates as a function of time since intake in urine and oral fluid with the chosen cutoffs, with a high degree of probability for detection at least 24 h after intake of a low therapeutic dose. This demonstrates the usefulness of oral fluid as a test matrix to assess adherence to ADHD medications, provided that the analytical method is sensitive, requiring a cutoff as low as 0.1 ng/mL for methylphenidate. Detection windows similar to those in urine may be achieved for amphetamine and methylphenidate in oral fluid.