A Parallel-Column LC–MS/MS Method for High-Throughput Analysis of Eight Antiepileptic Drugs in Clinical Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM), the practice of measuring drug plasma concentrations at multiple times, is necessary in the clinical management of drugs with narrow therapeutic windows, such as antiepileptic drugs (AEDs). This study describes a parallel two-column LC–MS/MS system for quantitative high-throughput analysis of AEDs in human plasma. It multiplexes two high-performance liquid chromatography (HPLC) systems into a single mass spectrometer, providing a twofold throughput increase compared to a generic single-column LC–MS/MS system. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The intra-day precision and inter-day precision for the analysis of the eight AEDs were less than 7.62%, with the accuracy ranging between −5.06 and 14.00%. The method was used to monitor plasma levels of eight AEDs from 1773 patients on a regular basis. The parallel HPLC–MS/MS method has been demonstrated to be capable of processing large analytical samples. With a twofold increase in sample throughput and a better-coordinated workflow, the system can easily meet the high-throughput challenge in clinical TDM.