In the clinic,
ethosuximide is commonly used to treat
generalized absence seizures but has recently been repurposed for other diseases. Because of adverse effects and drug interactions, high-throughput therapeutic drug monitoring of
ethosuximide is necessary. Microextraction is a simple, effective, rapid, and low consumption of organic
solvents method for sample preparation. In this study, microderivatization-increased detection (MDID)-combined microextraction was used to detect
ethosuximide by mass spectrometry.
Ethosuximide is a difficult to retain and ionize compound in the C18 nano-flow column and ionization interface, respectively. Hence, we developed a fast method for detecting
ethosuximide in human plasma by using the MDID strategy (within 2 min). Chemical microderivatization parameters were studied and optimized to increase the sensitivity of
ethosuximide detection at trace levels. The linear range for the analysis of
ethosuximide in 10 μL plasma was 5-500 μg/mL with a coefficient of determination (r2) ≥ 0.995. The precision and accuracy of intraday and interday analyses of
ethosuximide were below 13.0%. Furthermore, modifications of major
proteins in plasma and blood cells, induced by
ethosuximide, were identified. The proposed method effectively utilizes microliter samples to detect drug plasma concentrations under suitable microextraction procedures toward the eco-friendly goal of low consumption of organic
solvents. Graphical abstract ᅟ.