Evaluation of Three Quantification Methods for Monitoring Twelve Antiseizure Medications in Human Plasma by LC-MS/MS

The concentration of antiseizure medications in vivo has a significant influence on therapeutic and adverse effects. To use antiseizure medications safely and rationally, it is crucial to establish a method of measuring their blood concentration, provide individualized medication guidance to patients, and avoid adverse effects through therapeutic drug monitoring. Therefore, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the rapid detection of antiseizure medication concentrations in blood and applied it to the monitoring of clinical antiseizure medication therapy.

A Waters HPLC-ESI TQ-D with a Waters BEH C18 column (50 × 2.1 mm, 1.7 µm) was used; the blood samples were injected after protein precipitation in 50% methanol in water, and the analysis was conducted within 3.5 minutes. The ion source for mass spectrometry was an electrospray ionization source with the multiple ion reaction monitoring mode. An isotope standard was selected as the internal standard.

The linearity of each epileptic drug was good in the studied concentration range (R2 > 0.9930), and the lower limit of quantification was 0.01-8.00 mcg/mL, with intraday and interday precision less than 15.00%. The recoveries of the method ranged from 91.86% to 113.97%, and the stability of the method was good and unaffected by matrix effects.

The established LC-MS/MS method for the determination of antiseizure medication concentration was characterized by a simple operation procedure, short analysis time, high sensitivity, and good accuracy, providing a simple and reliable assay for the monitoring of antiseizure medication therapy.