Compliance testing of patients in ADHD treatment with lisdexamphetamine (Elvanse®) using oral fluid as specimen

Abstract

Pharmacological treatment of the attention-deficit/hyperactivity disorder (ADHD) includes use of the psychostimulant amphetamine. Non-adherence to medication is a well-documented problem in ADHD treatment and a cause of treatment failure. The study evaluated the possibility of using oral fluid for compliance monitoring during treatment with lisdexamphetamine (Elvanse®). UPLC-MS/MS methods for general oral fluid drug testing, lisdexamphetamine and amphetamine quantification and chiral analysis of amphetamine were used. The applied measuring ranges were 1-500 ng/mL for amphetamine and 0.01-15 ng/mL for lisdexamphetamine. Amphetamine (racemic) was detected and quantified in 98 (96%) of the 102 samples. The concentrations ranged from 2 to 8410 ng/mL. In 17 of these, the chiral analysis demonstrated intake of illicit amphetamine because L-amphetamine was present. The median D- + L-amphetamine concentration in the compliant group was 280 ng/mL, while the median concentration in the non-compliant group was statistically higher, 1677 ng/mL. In the non-compliant cases where L-amphetamine was detected, the L/D-amphetamine ratios ranged from 0.75 to 13.1 with a median of 1.0. Lisdexamphetamine was detected and quantified in 76 of the 102 cases, which represent 79% of the 98 cases with detected oral fluid amphetamine. The concentrations ranged from 0.01 to 6895 ng/mL. Drug testing had a positive rate of 23% in patients not taking illicit amphetamine and 82% among non-compliant patients with detected L-amphetamine. In conclusion, the study demonstrated the value of measuring amphetamine with a chiral method to detect intake of illicit amphetamine and to perform drug testing in oral fluid as a mean for compliance monitoring.

Keywords: ADHD; ADHD, attention-deficit/hyperactivity disorder; AcCN, acetonitrile; Amphetamine; Chiral analysis; LDX, lisdexamphetamine; LLOQ, lower limit of quantification; LOD, limit of detection; Liquid chromatography-mass spectrometry; Lisdexamphetamine; MeOH, methanol; OF, oral fluid; Oral fluid; UPLC-MS/MS, ultra-performance liquid chromatography – tandem mass spectrometry.