Abstract / Summary
Abstract Background Therapeutic drug monitoring (TDM) may improve treatment efficacy and reduce adverse effects in youth with attention-deficit/hyperactivity disorder (ADHD). However, data regarding drug concentration patterns according to sampling time and the clinical significance of drug level monitoring remain limited. Methods We collected a total of 355 urine and 236 plasma samples from 311 ADHD patients receiving methylphenidate (MPH). Levels of methylphenidate (MPH) and ritalinic acid (RA) were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Comprehensive assessments of ADHD symptoms were conducted on the same day, immediately after urine or blood sample collection. Behavioral symptoms and neuropsychological function in ADHD patients were evaluated. Results Our analysis revealed that median urinary concentrations of MPH and RA were 346.6 µg/mL (quartile (Q)1 – Q3: 89.05–893.8) and 19,968.8 µg/mL (Q1 – Q3: 5,898.9–53,311.3), respectively, with > 4 h post-dose identified as the optimal urine collection interval. Median plasma concentrations of MPH and RA were 8.15 ng/mL (Q1 – Q3: 4.68–11.95) and 201.85 ng/mL (Q1 – Q3: 111.28–304.6), respectively. Weak-to-moderate correlations were observed between plasma and urinary analyte levels, including MPH ( r = 0.297, p < 0.001), and plasma MPH versus urinary RA ( r = 0.280, p < 0.001). Plasma-based TDM demonstrated greater clinical relevance than urine-based monitoring, showing significant associations with manifestations of target response, variability in response consistency, ability to shift between tasks, and inconsistency in reaction times over longer intervals. Conclusions This study provides new insights into TDM in ADHD patients for optimizing therapeutic strategies, which may provide a foundation for future longitudinal studies.