Abstract
The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.
Highlights
About 70 million people worldwide suffer from epilepsy, a neurological disease that negatively affects patients’ quality of life and that of their families
Antiepileptic drugs (AEDs) possess a long tradition in the treatment of different modes of epilepsy and over the decades many analytical methods have been developed for the therapeutic monitoring of AEDs
The purpose of this review is to present bioanalytical methods applied for quantification of near thirty AEDs of the 1st–3rd generation of brivaracetam (BRV), carbamazepine (CBZ), clobazam (CLB), eslicarbazepine acetate (ESL), ethosuximide (ESM), felbamate (FBM), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), perampanel (PER), phenobarbital (PHB), phenytoin (PHT), fosphenytoin (FOS), piracetam (PIR), pregabalin (PGB), primidone (PRM), oxcarbazepine (OXC), rufinamide (RFM), stiripentol (STP), sulthiame (STM), tiagabine (TGB), topiramate (TPM), valproic acid (VPA), vigabatrin (VGB) and zonisamide (ZNS) and the cenobamate (CNB), the newest AED, in biological fluids, and designed to be used in therapeutic drug monitoring (TDM) in epilepsy patients
Summary
About 70 million people worldwide suffer from epilepsy, a neurological disease that negatively affects patients’ quality of life and that of their families. Antiepileptic drugs (AEDs), despite many scientists’ and the medical community’s efforts, are still the basic tool in the treatment of patients with epilepsy, a disease of unknown etiology. About thirty first–third generation AEDs are used in various types of epilepsy. AEDs possess a long tradition in the treatment of different modes of epilepsy and over the decades many analytical methods have been developed for the therapeutic monitoring of AEDs. More improved liquid chromatography (LC) methods have appeared in the last years, based mainly on sensitive mass spectrum detection. The elaborated methods are focused on determining many AEDs and their metabolites in one analytical run. The main problem of recent years has been developing procedures for sample micronization and automatic preparation of clinical material for quantitative determination. Microextraction techniques like solid-phase microextraction (SPME), single-drop microextraction (SDME), or dispersive liquid-liquid
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