Therapeutic Drug Monitoring of Clobazam, Perampanel, and Lacosamide Using a UPLC‐MS/MS Method: Analysis of 5‐Year Experience in a Large Cohort of Pediatric Epilepsy Patients From China

This study aims to develop an ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method to quantify clobazam, perampanel, and lacosamide plasma concentrations in pediatric epilepsy patients. Elution was performed using a gradient elution program, with a mobile phase composed of 0.01% formic acid in water and 0.01% formic acid in acetonitrile. The flow rate was 0.6 mL/min. The injector temperature was 10°C. The injection volume was 4 μL. Linearity, sensitivity, precision, accuracy, specificity, carryover, and extraction recovery were evaluated. Therapeutic drug monitoring data of 1132 samples were analyzed. The method was linear within 10-600 ng/mL, 100-2000 ng/mL, and 1.0-30.0 μg/mL for clobazam, perampanel, and lacosamide, respectively (r ≥ 0.998). The results indicated that the within-run and between-run precision coefficient of variation (CV %) did not exceed 15.0%, and that the accuracy (bias) ranged from -8.3% to 13.6%. Recovery ranged from 90.9% to 108.1%. All plasma samples could be maintained for up to 3 h at ambient temperature, 24 h at 4°C, 30 days at -30°C, and after successive freeze-thaw cycles in the absence of significant degradation. We successfully developed a simple and rapid LC-MS/MS method for the simultaneous measurement of three new generation ASMs, and successfully applied it to clinical practice.