Hydrophilic Interaction Liquid Chromatography (HILIC) as a Powerful Tool for the Determination of Antiepileptic Drugs: A Critical Review

Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation.