1. Therapeutic Drug Monitoring of 6 New-Generation Antiseizure Medications Using a Mass Spectrometry Method: Analysis of 2-Year Experience in a Large Cohort of Korean Epilepsy Patients.
- Author
-
Kim SM, Heo WY, Oh H, Joo EY, Shon YM, Hong SB, Lee SY, and Seo DW
- Subjects
- Humans, Female, Male, Republic of Korea, Adult, Middle Aged, Adolescent, Young Adult, Pyridones therapeutic use, Pyridones blood, Pyridones analysis, Chromatography, Liquid methods, Nitriles therapeutic use, Triazoles therapeutic use, Triazoles blood, Pregabalin therapeutic use, Pregabalin blood, Aged, Gabapentin therapeutic use, Gabapentin blood, Child, Vigabatrin therapeutic use, Vigabatrin blood, Cohort Studies, Acetamides therapeutic use, Acetamides blood, Acetamides analysis, Aniline Compounds therapeutic use, Aniline Compounds blood, Aniline Compounds analysis, Child, Preschool, Reproducibility of Results, Anticonvulsants therapeutic use, Anticonvulsants blood, Drug Monitoring methods, Epilepsy drug therapy, Epilepsy blood, Tandem Mass Spectrometry methods, Lacosamide therapeutic use, Lacosamide blood
- Abstract
Context.—: New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce., Objective.—: To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy., Design.—: Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on an Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed., Results.—: The method was linear with limit of detection less than 0.05 μg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals for all 6 ASMs., Conclusions.—: A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. These large-scale TDM data could help establish an effective monitoring strategy for these drugs., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2025 College of American Pathologists.)
- Published
- 2025
- Full Text
- View/download PDF