High performance liquid chromatography: A versatile tool for assaying antiepileptic drugs in biological matrices

Epilepsy is a recurrent long-term illness occurring in approximately 1.0% of the world's population. There are currently about 29 approved antiepileptic drugs for the management of epilepsy. Due to narrow therapeutic indices of most antiepileptic drugs, clinical pharmacokinetic characteristics and therapeutic drug monitoring of these drugs are imperative. The objectives of this review were to identify common chromatographic principles, requirements and/or conditions for high-performance liquid chromatography as applied to assay of antiepileptic drugs in biological matrices. The review was conducted using 66 peer reviewed articles (1990 to 2020) from 29 journals that were sought via PubMed, Science Direct and Google Scholar. In all, 29 antiepileptic drugs were assayed from 6 different biological matrices. Forty-three of the reviewed articles estimated the concentration of only one antiepileptic drug, whilst 23 articles focused on simultaneous determination of two or more antiepileptic drugs. Thirty-four, 20, and 14 articles reported using liquid-liquid extraction, protein precipitation, or solid phase extraction for sample clean up, respectively. The ratio of reversed-phase to normal phase, LC-UV to LC-MS and isocratic elution to gradient elution were 61:3, 43:7 and 55:11, respectively. With the exception of one article the reported recoveries ranged from 60.3% to 109.6%. It is noteworthy, that, the performance metrics of high-performance liquid chromatography are better compared to other assays of antiepileptic drugs in biological matrices. This review describes the relevant liquid chromatographic method conditions over the past 30 years for the analysis of this class of drugs, which provides a basis for further method development and optimization.